Cervical screening: laboratories providing HPV testing and cytology services in the NHS Cervical Screening Programme

Question 1

1. Primary hrHPV testing

Accepted Answer

The hrHPV primary screening test is now performed on all cervical screening samples taken in the NHSCSP. In the primary hrHPV screening pathway, cytology is used as a triage test in women where hrHPV is detected to determine whether immediate referral to colposcopy is required. The majority of abnormal cytology results lead to colposcopy referral – a glandular neoplasia (non-cervical) result will normally be referred for a gynaecological opinion.

The NHSCSP has evaluated the available hrHPV tests with appropriate liquid-based cytology samples. You can use any of the NHSCSP approved hrHPV tests for primary hrHPV testing.

The NHSCSP must approve any new tests or modifications to existing tests prior to implementation. We have produced guidance for accepting new hrHPV tests for use in the programme, and guidance for laboratories on HPV quality control and assurance.

Virology testing services must be co-located with the cervical cytology service although not necessarily within the same department or the same organisation. A Public Health England (PHE) virology service for example can be located on the same site as an NHS cervical screening laboratory.

A service level agreement (SLA) must be in place:

where the virology service is provided separately from the cytology service
for virology support from a consultant virologist where hrHPV testing is carried out within the cytology laboratory

1.1 Acceptable cervical samples

The NHSCSP provides detailed guidance for the reduction of administrative and technical errors associated with cervical screening sample requests. Sample takers must provide the requested information to enable laboratories to accept and process samples.

Sample takers must take samples at the specified intervals. Currently, normal recall intervals are 3-yearly for women aged 25 to 49 and 5-yearly for women aged 50 to 64. Women known to be HIV (human immunodeficiency virus) positive should be offered annual screening. Where a sample taker notifies the laboratory of a woman’s HIV positive status and her test is negative then the laboratory must issue a report with a 12-month recall.

1.2 HPV test unavailable (infection code U)

The primary screening test is an hrHPV test. Insufficient cellular material to provide a reliable hrHPV result means the sample is also unsuitable for cytological assessment and must be classified as invalid and coded as U.

The test should be repeated in no less than 3 months (code X, U, R3).

1.3 Negative hrHPV test (infection code Ø)

Women attending for a routine screening test who have a negative hrHPV test result are returned to routine recall (code X, 0, A).

1.4 Positive hrHPV test (infection code 9)

All women with a positive hrHPV test have cytology triage performed.

Question 2

2. Reporting hrHPV tests and use of HPV unavailable (HPV-U) category

Accepted Answer

We are developing a new standard for unavailable hrHPV test results, coded as HPV-U. Shadow reporting started in 2019 and we will establish new thresholds when sufficient data are collected and analysed. This also applies to women referred to colposcopy for 2 inadequate tests for whatever reasons.

2.1 Sample internal control (endogenous): definition

The internal control signal in samples serves to confirm that each sample:

has sufficient cell input for accurate hrHPV detection
was processed correctly
indicates if inhibitors of amplification are present

2.2 Test run control (exogenous): definition

Test run controls include a positive and negative control provided with the kit, and one of each is required with every run. The negative control verifies that hrHPV contamination did not occur during the sample preparation and set-up of the amplification reaction.

2.3 Sample internal control not detected

HPV platforms with sample internal controls report an invalid result when the sample internal control (for example, β-globin) result is negative or invalid in hrHPV negative samples. A repeat test is performed starting with sample preparation. If there is still no valid result, report the sample as HPV-U.

Where the sample internal control is negative or invalid, an hrHPV positive result remains valid and is reported as such.

HPV genotyping for hrHPV 16 and 18 is provided automatically by some HPV platforms alongside an hrHPV positive result. HPV 16 or 18 results have been used to manage women in a small number of laboratories participating in primary HPV screening pilots.

You can still report a positive test result for HPV 16, 18 or HPV O (other HPV types) on platforms which genotype, despite the internal control returning a negative or invalid result, report these tests as HPV positive.

2.4 Failed samples note

HPV platforms report error codes, or flags due to insufficient volume or clot detected, as failed samples. Report insufficient samples as HPV-U. A repeat test is performed on clot detected samples starting with sample preparation. If the sample fails again, report it as HPV-U.

The user is alerted by a flag or error code when samples cannot be reported due to failure of test run controls, or fail due to instrumentation errors or failures. The user should resolve the problem and retest the samples. If subsequently no result is obtained due to insufficient sample, reported this as HPV-U as above.

2.5 SurePath samples with broom head missing or ThinPrep samples with broom head present

Report samples testing hrHPV positive as HPV positive. Report subsequent cytology as inadequate unless abnormal cells are found.

Report samples testing hrHPV negative as HPV-U, log the error and notify the sample taker.

2.6 Out of programme samples and major labelling discrepancies

Reject these samples (see NHSCSP guidance on sample acceptance). You must not report them as HPV-U.

2.7 Cervix not visualised and, or no 5 x 360 degree sweep

These samples are accepted by the laboratory and HPV tested. As there is no guarantee that a suitable sample was obtained, report these samples, if hrHPV negative, as HPV-U. If hrHPV positive, prepare and examine a cytology slide. You must report this as cytology inadequate unless you identify abnormal cells. Explain why it is reported this way in the report text to the sample taker.

2.8 Samples received in out-of-date vials or vials expired before testing

Reject these samples. They must not be reported as HPV-U.

2.9 Samples beyond the recommended or approved storage time for an hrHPV test, and within vial expiry date

Carry out hrHPV testing and report the result if hrHPV positive. Report subsequent cytology only if the laboratory can prepare the slide within 6 weeks of the sample being taken and provided they have stored it between 15 and 30 degrees Celsius. Beyond 6 weeks, the laboratory cannot prepare a slide and must report the sample as cytology inadequate.

Samples testing hrHPV negative should be reported as HPV-U.

2.10 Sample vials that have leaked

Provided there is sufficient volume according to the manufacturer’s advice, hrHPV test these samples and report the result if hrHPV positive. You can report subsequent cytology providing there is sufficient residual sample for processing. If insufficient volume, report as cytology inadequate.

Report samples testing hrHPV negative as HPV negative.

2.11 Samples contaminated with blood and/or mucus

Samples should be hrHPV tested and the result reported. Refer to the manufacturer’s guide for maximum concentration of blood that does not cause interference with test performance. Samples contaminated by blood and/or mucus that test hrHPV positive where there are insufficient cells, such that they are interpreted as cytologically inadequate, must be reprocessed and treated as per the manufacturer’s guidance.

Question 3

3. Cervical cytology samples

Accepted Answer

3.1 Cervical cytology sample: definition

A sample of cells taken from the cervix using a Cervex™ brush and transferred to a glass slide using an approved liquid-based technology.

3.2 Vaginal vault sample: definition

A sample of cells taken from the vaginal vault using a Cervex™ brush and transferred to a glass slide using an approved liquid-based technology. Vault samples are outside the cervical screening programme.

3.3 BD focal point slide profiler

This system has not been evaluated for use in a setting where the primary screening test is an hrHPV test and is not currently approved for use in clinical practice in the NHSCSP.

3.4 Adequacy of cervical cytology samples

Laboratories must follow the guidance on adequacy published in a study by The National Institute for Health Research Health Technology Assessment in 2015. For the liquid-based cytology systems used in the UK, a minimum acceptable cell count of 15,000 for SurePath™ and 5,000 for ThinPrep™ would achieve the best balance between maintaining low levels of inadequate slides and not compromising the chances of detecting abnormalities.

3.5 Cell counting methodology

Perform cell counting if the adequacy of the preparation is in doubt.

Calculate the total cell count as: (mean cell count of 10 high power fields) x (area of cell deposit) ÷ (area of ocular).

The methods are documented in the Health Technology Assessment (HTA) Adequacy Report. Refer to Appendix 3 and Appendix 4.

Question 4

4. Reporting and classification of cervical cytology

Accepted Answer

4.1 Cytology classification and reporting codes

The table below lists the cytology classification and cytology reporting codes which are used in routine reporting practice on hrHPV positive samples.

Table 1: List of cytology classification and cytology reporting codes

Cytology reporting classification	Result code	Call and recall codes for triage and test of cure
Inadequate cytology	1	-
Negative cytology	2	N
Borderline change in squamous cells	8	B
Borderline change in endocervical cells	9	E
Low-grade dyskaryosis	3	M
High-grade dyskaryosis (moderate)	7	-
High-grade dyskaryosis (severe)	4	-
High-grade dyskaryosis/?invasive squamous carcinoma	5	-
?Glandular neoplasia of endocervical type	6	-
?Glandular neoplasia (non-cervical)	Ø	G

4.2 Inadequate for cytology triage (result code 1)

A sample can have sufficient material to provide a valid hrHPV result but the subsequent cytology preparation may not have sufficient epithelial cells for reliable interpretation. In this case, report the sample as inadequate for cytology. The test should be repeated in no less than 3 months (code 1, 9, R3). This also applies to women referred to colposcopy for 2 inadequate tests for whatever reasons (code 1, 9, S).

Report a sample where the sample taker has not visualised the cervix or not performed a 5 x 360 degree sweep and the result is hrHPV positive as cytology inadequate if no abnormal cells are identified.

Do not report a cytology sample as inadequate, however scanty, if it contains abnormal cells.

4.3 Cytology negative (result code 2)

Classify adequate samples with no abnormal cells as negative (2, 9, R).

4.4 Dyskaryosis

Features such as abnormal nuclear outlines or raised nuclear:cytoplasmic ratios can create a strong suspicion of dyskaryosis. Note that these alone are insufficient for definitive diagnosis in the absence of an abnormal chromatin pattern. You can find detailed definitions of abnormal chromatin and other features in guidance published by the British Association for Cytopathology^{[footnote 3]}.

4.5 Grading squamous dyskaryosis

Define the grade of dyskaryosis by determining the ratio of nuclear diameter to cytoplasmic diameter ^{[footnote 2]} ^{[footnote 3]}.

Low grade dyskaryosis (result code 3)

This is indicated by the presence of dyskaryotic cells with a nuclear:cytoplasmic diameter ratio of less than 50%. Such cells can also show koilocytosis, indicated by the presence of a large, sharply defined, clear perinuclear halo, surrounded by a condensed rim of cyanophilic or eosinophilic cytoplasm.

Do not describe the presence of koilocytosis or other morphological features of HPV infection in the report.

High grade dyskaryosis (moderate) (result code 7)

Use this code when dyskaryotic cells are present with a nuclear:cytoplasmic diameter ratio of more than 50% and less than 75%. Distinguishing precisely between high grade dyskaryosis (moderate) and high grade dyskaryosis (severe) is difficult and not fully consistent.

High grade dyskaryosis (severe) (result code 4)

Use this code when dyskaryotic cells are present with a nuclear:cytoplasmic diameter ratio of more than 75%.

4.6 Difficulties in grading dyskaryosis

When the cells and their nuclei are not circular, the nuclear:cytoplasmic diameter ratio will depend on the axis of measurement. In this case, the axis that produces the maximum nuclear:cytoplasmic ratio should determine the grade.

There may be rare occasions when dyskaryosis is present but cannot be graded. This usually occurs where cytoplasm has been lost due to severe cytolysis or atrophy or where cell boundaries cannot be seen. Code such cases as high grade dyskaryosis (moderate) and provide a free text explanation if the laboratory reporting system allows.

4.7 Difficulties in the identification of dyskaryosis

Scanty abnormal cells

The presence of just one abnormal cell is sufficient for a report of abnormality. Sometimes dyskaryotic cells can be extremely sparse.

Hyperchromatic crowded cell groups (HCCGs)

Take care to examine all HCCGs to differentiate between abnormalities (which can be squamous or glandular), normal cells (including endometrial and endocervical cells), and normal changes (including metaplastic and atrophic changes, as well as repair and regeneration).

Pale cell dyskaryosis

Dyskaryotic cell nuclei stain to varying intensities and you can see truly pale dyskaryosis in LBC samples.

Bland dyskaryosis

The chromatin pattern in bland dyskaryosis appears only slightly abnormal (usually a degree of hyperchromasia is present). Cells are arranged in groups with abnormal architecture^{[footnote 4]}.

Small cell severe dyskaryosis

A monotonous population of cells showing an abnormal chromatin pattern is present. The nuclear diameter of an affected cell is no more than twice that of a neutrophil polymorphonuclear leucocyte.

Unless care is taken to identify the cell type, small cell severe dyskaryosis can be mistaken for:

immature metaplastic squamous cells
endometrial cells
lymphocytes
histiocytes

Take care to distinguish the following cell types and conditions from dyskaryosis:

follicular cervicitis
changes caused by the herpes simplex virus
endometrial or endometrioid cells
lower uterine segment sampling (this can be a particular problem in women who have been treated by trachelectomy)
metaplastic cells
changes of repair and regeneration

4.8 High grade dyskaryosis/?invasive squamous cell carcinoma (result code 5)

Well-differentiated, keratinising squamous cell carcinoma presents with:

bizarre keratinised cells
fibre and tadpole cells
keratinised cytoplasmic debris

Poorly-differentiated squamous carcinomas do not show these features and are characterised by:

marked variation in cellular shape and size
an especially coarse granular chromatin pattern
and an altered chromatin distribution that results in nuclear ‘windowing’ or translucencies

Enlarged, irregular and multiple nucleoli can sometimes be present.

A malignant diathesis is uncommon. When present, it is characterised by small collections of thin proteinaceous material with accompanying fragments of leucocytes and red blood cells.

In SurePath™ preparations diathesis tends to be grey or blue in colour and is often closely associated with the malignant cells (known as ‘clinging diathesis’).

In ThinPrep™ preparations, lysed blood, which is always a component of diathesis, tends to be located around the periphery of the deposit, and can appear red in colour. Other fragments of debris may be distributed throughout the specimen.

4.9 ?Glandular neoplasia of endocervical type (result code 6)

Report samples as ‘glandular neoplasia of endocervical type’ if they show cytological features suggestive of cervical glandular intraepithelial neoplasia (CGIN) or endocervical adenocarcinoma^{[footnote 2]}.

These features include more numerous of groups of endocervical cells which can appear to be normal or abnormal. The normal architecture of these groups is lost, especially the honeycomb or picket fence arrangements.

The abnormal groups contain cells with crowded, round, oval or elongated nuclei. The nuclei usually have evenly distributed finely or moderately granular chromatin with absent or inconspicuous nucleoli.

The groups may have an acinar arrangement, rosette formation or strips with pseudostratified nuclei. Loosely cohesive cells at the surface of curved cell groups tend to be tapered and spread out rather like feathers on the trailing edge of a wing; a feature known as feathering^{[footnote 5]}.

The presence of a background diathesis in these samples normally suggests invasion. Other features suggestive of cervical adenocarcinoma are a large number of groups of abnormal endocervical cells with variation in nuclear size between the groups. You should exercise caution as the cytomorphological features of high grade CGIN and early endocervical adenocarcinoma overlap.

4.10 Differentiating high grade squamous dyskaryosis and glandular neoplasia

It can be difficult to distinguish these abnormalities from one another, and both can be present in the same sample. One factor favouring a report of glandular neoplasia is the presence of HCCGs with radial architecture and loose edges. The presence of HCCGs with tightly defined edges and a lack of architectural organisation favour a report of high-grade squamous dyskaryosis.

Ideally, you should distinguish the 2 types of abnormality from one another, although this may not be possible as some groups do not show clear features of either squamous dyskaryosis or glandular neoplasia.

4.11 ?Glandular neoplasia (non-cervical) (result code Ø)

You may identify cells from a non-cervical adenocarcinoma in a cytology sample after a positive hrHPV test. These cells can present singly, in small clusters (including acinar or papillary formations), as highly vacuolated groups, and/or in HCCGs. This is likely to be an incidental finding as most, if not all, non-cervical cancers are unlikely to show HPV positivity.

Nuclear morphology varies from the relative uniformity of well-differentiated carcinomas to the highly pleomorphic nuclei of high-grade undifferentiated tumours^{[footnote 2]}. You may see features supporting a diagnosis of endometrial, ovarian, or metastatic lesions from beyond the genital tract. Describe these in free text^{[footnote 2]}.

You should attempt to distinguish these cases from endocervical glandular abnormalities, as both need different management. Non-cervical glandular abnormality requires urgent referral for a gynaecological opinion, not colposcopy.

Difficulties in the identification of non-cervical glandular neoplasia

Changes associated with intrauterine contraceptive devices (IUCDs) include clusters of highly vacuolated cells. These clusters are usually few in number, and the cells show minimal nuclear atypia, and have thin-walled, punched-out vacuoles that may contain ingested but intact polymorphs.

Occasionally it can be difficult to distinguish between such groups and vacuolated forms of adenocarcinoma as both types of abnormality show coalescent, debris-filled, vacuolated cytoplasm. The nuclear pleomorphism that characterises adenocarcinoma is a useful distinguishing feature.

Psammoma bodies in a cervical sample are a rare and potentially sinister finding, warranting appropriate investigations to exclude neoplasia of the female genital tract or peritoneum. Malignancy is most likely to be found in women who have atypical cells in the sample, are over 45 years of age, and are symptomatic. In the absence of definite cytological atypia, you should include reactive processes such as chronic endocervicitis, endometritis, or IUCD effect in the differential diagnosis^{[footnote 6]}.

Although such a slide is technically negative for the purpose of cervical cytology triage, you must inform the sample taker of the differential diagnosis in free text so they can plan appropriate clinical management.

You can generally identify endometrial cells in LBC specimens, despite general acceptance that the sampling method has a low sensitivity for detecting endometrial disease. You must assess the cytological features of any endometrial cells to determine their potential clinical significance and to guide appropriate management.

4.12 Borderline change in squamous cells (result code 8)

The term ‘borderline change in squamous cells’ describes morphological alterations to squamous cells that cannot be identified with certainty as the consequence of inflammatory, reactive, metaplastic, or hormonal processes. Examine borderline samples carefully to make sure that dyskaryosis is not missed.

Cells showing borderline change form a distinct population that can be differentiated from surrounding cells of the same type. The cells lack either sufficient nuclear abnormality or koilocytosis to justify a report of dyskaryosis. The abnormal cells can be binucleate and the nuclei can be enlarged, pyknotic, or show slightly irregular membranes. Cells showing borderline change can also be dyskeratotic, forming either orangeophilic sheets or clumps with intracytoplasmic keratin.

Difficulties in the identification of borderline change in squamous cells

You should not confuse dyskeratosis with parakeratosis in cells with normal nuclei. Parakeratotic cells may form small ‘rafts’ or ‘pearls’, and you should not report these as borderline groups. Additionally, you may see orangeophilic cells with small pyknotic nuclei and a low nuclear:cytoplasmic ratio in atrophic samples. You should take care to distinguish these from cells showing borderline change.

Inflammation, sometimes associated with atrophic vaginitis, non-specific cervicitis, or endocervical polyps, can increase the nuclear:cytoplasmic ratio, making cells appear immature. You may suspect high grade dyskaryosis where the nuclear:cytoplasmic ratio is high. As noted previously, a high nuclear:cytoplasmic ratio is not sufficient to diagnose dyskaryosis. Inspection of the chromatin should allow a confident diagnosis of inflammatory changes.

Even in the absence of features suggesting inflammation or repair, metaplastic squamous cells can show hyperchromatic, clumped chromatin. This mimics dyskaryosis and can be degenerative in nature. According to the grading criteria, dyskaryosis in metaplastic cells will almost likely be high grade. You should pay attention to the whole cell, as the cytoplasmic features that typify immature metaplasia tend not to be found in cases of true dyskaryosis.

Atrophic changes are seen as sheets of parabasal cells with a relatively high nuclear:cytoplasmic ratio, due to loss of oestrogenic cytoplasmic maturation. Clumped chromatin, which mimics dyskaryosis, may be present and cells can appear either as separated parakeratotic entities or as HCCGs. You should assess these cells in relation to the slide as a whole, as dyskaryotic cells usually form a separate population that is distinguishable from the background cell pattern.

4.13 Borderline change in endocervical cells (result code 9)

As with borderline change in squamous cells, you should use borderline change in endocervical cells when you cannot identify dyskaryosis with certainty. You should report cases meeting the criteria for glandular neoplasia as such.

Typically, cell groups show either architectural or nuclear features suggesting CGIN. For example, there may be crowded cells with pseudostratification but little nuclear abnormality, or coarsely clumped chromatin with entirely normal architecture.

Borderline change in endocervical cells should be a rare diagnosis. We recommend the application of objective criteria and consensus reporting to maintain the specificity of the category and avoid unnecessary colposcopy.

Difficulties in the diagnosis of borderline change in endocervical cells

Cervicitis and polyps can produce reactive changes in endocervical cells, and these may mimic glandular neoplasia. Inspection of both the architecture and the nuclear features of the groups should exclude neoplasia in most cases, allowing a confident negative diagnosis.

Most cases of tuboendometrioid metaplasia (TEM) and lower uterine segment sampling (LUS) should be confidently recognised and reported as negative. HCCGs may occasionally mimic either high grade squamous dyskaryosis or (less commonly) glandular neoplasia. A diagnosis of ‘borderline change in squamous cells’ or ‘borderline change in endocervical cells’ is appropriate to these situations.

There is no consensus on the category of borderline change in endometrial cells and this must not be used^{[footnote 7]}.

4.14 Reporting of borderline change in HPV positive samples

A significant number of hrHPV positive samples show no cytological abnormality. Take care not to alter the morphological criteria described above in the context of hrHPV primary screening.

4.15 Reporting multiple diagnoses

Cervical abnormalities with co-existing non-cervical glandular neoplasia

In rare cases, a woman’s cytology test may reveal the co-existence of non-cervical glandular neoplasia with cervical abnormalities. Treatment of the former falls outside the scope of the screening programme. You must record the cervical abnormality as the cytology test result and therefore determine the woman’s management. This will make sure the woman is subject to appropriate NHSCSP failsafe systems.

The presence of a non-cervical glandular abnormality is potentially more serious than cervical dyskaryosis and requires urgent gynaecological referral. From a screening point of view, if there is a cervical abnormality then this should be the result issued and you should record the non-cervical glandular abnormality in the report.

This is a rare situation and the reporter must communicate with colposcopy colleagues at the time of reporting to arrange the appropriate management.

Women with 2 cervices

Multiple diagnoses can also be possible in a case where a woman has 2 cervices. The laboratory should receive separate samples labelled to identify which cervix they have come from.

The laboratory must have a system to:

maintain the identification of both samples
transmit only one result to PCSE (the worst-case scenario)

The report must record the result of both cervix samples.

4.16 Benign endometrial cells in cervical samples

The significance of cytologically benign endometrial cells in cervical samples varies. You can attribute this to the:

phase of the menstrual cycle
drug history
clinical history
age of the patient

Indicate in the clinical management advice provided if any of this information is unavailable.

Endometrial cells seen in a sample from a woman under age 45 is highly unlikely to indicate significant endometrial pathology^{[footnote 8]}. You do not need to report normal endometrial cells found in a cervical sample from a woman of this age.

In women over the age of 45, normal endometrial cells are significantly more likely to be found in the cervical sample up to day 12 of the menstrual cycle than in the remainder of the cycle, and need not be specifically reported by the laboratory.

In women aged over 45 who are beyond day 12 of the menstrual cycle, the finding of normal endometrial cells in a cervical sample can indicate endometrial pathology ranging from benign polyps to carcinoma. The association of normal endometrial cells in a cervical sample with significant pathology (endometrial hyperplasia and neoplasia) increases with age.

Normal endometrial cells found beyond day 12 of the menstrual cycle in an individual over 45 may not indicate pathology if the woman is receiving oral contraceptives, hormone replacement therapy, or tamoxifen, or where an IUCD has been fitted. If this information is on the request form, you should make an appropriate annotation or educational note in the free text section of the report. No further clinical action is required if no other clinical symptomatology suggests endometrial disease.

Always report normal endometrial cells identified in a sample from a woman aged 45 or over if the menstrual, drug history and contraceptive history are unknown (see above). Also report them if found in any postmenopausal woman, accompanied by a comment similar to the following:

‘Endometrial cells are present in a woman aged over 45. Such cells can be associated with endometrial pathology, particularly if out of phase or after the menopause. Consider referral for a gynaecological opinion in light of the menstrual, drug history and clinical history.’

If the day of the menstrual cycle is unknown, and the sample is otherwise negative, then you should report it as negative with a comment, for example:

‘Endometrial cells are present but menstrual history is not stated. Consider referral for a gynaecological opinion if there is any history of abnormal vaginal bleeding’.

Question 5

5. Management of women

Accepted Answer

5.1 Women with negative hrHPV tests

Women with a negative hrHPV result do not have cytology performed, and return to the routine screening interval relevant to their age.

A summary of the recommended management of women attending for screening can be found in the primary HPV screening protocol algorithm in section 8 of the guidance on programme and colposcopy management.

5.2 Women with positive hrHPV tests

Samples from women testing positive for hrHPV undergo cytology triage. Refer women with any grade of abnormal cytology to colposcopy immediately. This includes:

borderline changes in squamous cells
borderline changes in endocervical cells
low grade dyskaryosis
high grade dyskaryosis (moderate)
high grade dyskaryosis (severe)
high grade dyskaryosis ?invasive squamous carcinoma
?glandular neoplasia of endocervical type

Repeat test at 12 months for women with hrHPV and negative cytology

Recall women who test positive for hrHPV with negative cytology for a repeat test at 12 months. At this repeat test, women testing hrHPV negative are returned to routine screening.

Repeat test at 24 months for women with hrHPV persistence and negative cytology

Women returning for a second repeat test (24 months since the initial screening test) receive an hrHPV test. Women testing hrHPV negative are returned to routine screening. Women testing hrHPV positive have cytology triage performed and are referred to colposcopy at this stage regardless of whether the cytology result is inadequate, negative or abnormal.

?Glandular neoplasia (non-cervical)

Women with a ?glandular neoplasia (non-cervical) cytology result must have a gynaecological referral. Follow up these women for their hrHPV positive result in the same way as women with negative cytology by repeat screening at 12 months.

5.3 Samples without a valid screening result

Reject samples unsuitable for testing prior to logging or processing them (see the policy on sample acceptance). These samples are not reported as hrHPV Unavailable (HPV-U).

When the hrHPV test result is unavailable or cytology is inadequate at any screening episode in the pathway, repeat the sample in no less than 3 months. Women who have inadequate cytology at the 24 month repeat test are an exception and are referred to colposcopy. Women who have 2 consecutive unavailable or inadequate screening tests, in any combination, are referred to colposcopy.

Cytology is not performed on any sample where an hrHPV positive result has not been obtained, except for samples taken by novice sample takers.

5.4 Follow up of women who have attended colposcopy

The recommended follow up for women who have attended colposcopy following primary hrHPV screening is in section 8 of the guidance on programme and colposcopy management.

Women in follow up when primary hrHPV testing protocols are implemented

Women recently treated for Cervical Intraepithelial Neoplasia (CIN) or Cervical Glandular Intraepithelial Neoplasia (CGIN) prior to the implementation of primary hrHPV testing are managed in accordance with colposcopy management recommendations.

Women being followed up for untreated CIN1 are managed by hrHPV testing. Women part way through follow up for treated CIN, CGIN or untreated CIN1 should be managed by hrHPV testing at their next test and not continue with cytology-based follow up.

Women who have completed follow up

Women who have completed follow up when primary hrHPV testing is implemented and are returning for their next test (36 months later or after the routine recall interval) will begin a new screening episode in accordance with the primary hrHPV screening protocol algorithm.

Follow up of untreated CIN1

Women with untreated CIN1 are recalled for screening at 12 months with primary hrHPV testing. Women testing hrHPV negative at this repeat test are recalled in a further 36 months, at which point they re-start the screening protocol for primary hrHPV testing.

Women testing positive for hrHPV at the 12 month repeat test have cytology performed on their sample. If this is abnormal (any grade) they are re-referred to colposcopy. Women with negative cytology are recalled for screening in a further 12 months.

Women who are hrHPV negative at the second repeat test are recalled in 36 months when they will restart the screening protocol for primary HPV testing. Those who are hrHPV positive have cytology performed. Those testing negative for cytology can also be recalled in 36 months. Women with abnormal cytology are referred to colposcopy.

Women with untreated CIN following referral for high-grade cytology are managed in accordance with the colposcopy and programme management guidance.

Follow up of untreated CIN2

Women with untreated CIN2 are managed in accordance with the colposcopy and programme management guidance.

Follow up of treated CIN of any grade

Women treated for CIN of any grade must have a follow up hrHPV test 6 months post treatment. Recall those testing hrHPV negative for screening in 36 months when they will re-start the screening protocol for primary hrHPV testing, regardless of their age. Women who test hrHPV positive have cytology performed and are re-referred to colposcopy regardless of the cytology including inadequate results.

Follow up of treated CGIN or SMILE

Women adequately treated for CGIN or Stratified Mucin producing Intraepithelial Lesions (SMILE) that is with complete excision margins, are followed up with screening at 6 months post treatment. Test all samples for hrHPV and recall those women who test negative for the second follow up test in a further 12 months. If still HPV negative then recall at 36 months at which point they can restart the screening protocol for primary hrHPV testing.

Cytology evaluation is not required in hrHPV negative women to confirm the presence of endocervical cells.

Women who test hrHPV positive at first follow up have cytology performed and are referred to colposcopy (if not already under colposcopy management) regardless of cytology result. Recall women with negative or inadequate cytology and normal colposcopic appearance for the second follow up test in a further 12 months. The cytology samples from these hrHPV positive women must contain endocervical cells to be considered adequate for cytology (unless they contain abnormal cells).

When individuals are recalled for a second follow up test at 12 months, recall those testing hrHPV negative for further testing in 36 months when they re-start the screening protocol for primary hrHPV testing. Women testing hrHPV positive at the second follow up test have cytology performed and are referred to colposcopy (if not already under colposcopy management). Women with negative or inadequate cytology and normal colposcopic appearance continue to be called at 12-monthly intervals and managed in the same way as individuals who are attending for a second follow up test.

Women referred to colposcopy for abnormal cytology at either of the follow up tests are eligible to enter the post-treatment follow up pathway again if they have further re-excision with complete excision margins. We recommend annual follow up with hrHPV testing and cytology where indicated for 10 years for those women where colposcopy is normal or re-excision does not occur,

Follow up of incomplete excision of CGIN or SMILE

Women treated for CGIN or SMILE with incomplete excision margins are followed up with hrHPV testing at 6 and 12 months and then annual follow up for a further 9 years.

Refer back to colposcopy on the first HPV positive, regardless of cytology, those women who are under 10 years follow up after CGIN incompletely excised, or because of persisting HPV positivity and negative cytology. Report cytology as abnormal if abnormal cells are seen. The presence of endocervical cells is not required for a negative report. Report cytology as inadequate, if inadequate for other reasons.

Follow up of cervical cancer

Women being followed up clinically for cervical cancer and who still have a cervix are followed up with hrHPV testing at 6 and 12 months, and then annual follow up for a further 9 years.

In circumstances when a patient is treated conservatively for cervical cancer (for example, stage 1a1 two LLETZ treatments) and they return to annual review in the community, if their annual cervical screening test shows HPV positive they will require a direct referral to colposcopy regardless of cytology result.

Vaginal vault samples

Vaginal samples taken at follow up of women after hysterectomy fall outside the screening programme. The call and recall service does not issue a result letter or recall invitation.

The colposcopy and programme management guidelines describe the recommended follow up after hysterectomy (chapter 3, section 4.5).

Question 6

6. 
HPV and cytology result and action codes

Accepted Answer

Result and action codes used in primary hrHPV testing with cytology triage are given below.

6.1 HPV result codes

Ø (zero) hrHPV negative
9 (nine) hrHPV positive
U hrHPV result unavailable

Please note: Code Q (no hrHPV test carried out due to recent positive hrHPV test) is retired although it may be seen in a woman’s screening history.

6.2 Cytology result codes

X No cytology required
Ø * ?glandular neoplasia (non-cervical)
1 inadequate
2 negative
3 low grade dyskaryosis
4 high grade dyskaryosis (severe)
5 high grade dyskaryosis ?invasive squamous carcinoma
6 ?glandular neoplasia of endocervical type
7 high grade dyskaryosis (moderate)
8 borderline change in squamous cells
9 borderline change in endocervical cells

Please note: * non-cervical neoplasia treated as negative for NHSCSP management

6.3 Action codes

A routine recall
R early repeat (in 3, 6, 12 or 36 months)
S suspended from recall
H no action (for example, private tests)*

Please note: * Code H means ‘no action’ (or ‘do not change next-test-due-date’). It must only be used for negative and inadequate tests taken outside the UK cervical screening programmes.

Code H is not used for non-NHS tests that are abnormal.

6.4 Valid code combinations

The table below lists the valid cytology result, HPV result and action code combinations.

Table 2: valid code combinations

Cytology result code	HPV result code(s)	Action code(s)
X	0 or U	R
X	0	A
X	0 or U	S
Ø	9	R or S
1	9	R or S
2	9	R or S
3	9	S
4	9	S
5	9	S
6	9	S
7	9	S
8	9	S
9	9	S

Question 7

7. Clinical governance

Accepted Answer

Clinical governance is the system through which NHS organisations are accountable for continuously improving the quality of their services and safeguarding high standards of care by creating an environment in which clinical excellence will flourish (Department of Health & Social Care definition).

Clinical governance encompasses quality assurance, quality improvement and risk and incident management.

7.1 Commissioning arrangements

NHS England (NHSE) commissions all the services required to implement primary hrHPV testing and cytology triage according to the criteria and standards developed by PHE. The Section 7A service specification for cervical screening provides the details.

7.2 Information technology

PHE does not specify or commission the IT systems that support the operation of the NHSCSP. Systems must be fit for purpose across the full cervical pathway to support the safe implementation of HPV primary screening. The British Association of Cytology (BAC) Code of Practice outlines the principles of IT systems used in cervical cytology laboratories. Effective and safe IT systems must be in place within the laboratory, and between the laboratory and other laboratories and service users.

7.3 Automatic authorisation of primary HPV negative test results

Automatic authorisation will allow laboratories to:

reduce errors compared with manual systems (dependent on the quality of information supplied by sample takers and access to remote histology databases)
optimise staff working time
reduce laboratory turnaround times
standardise the laboratory approach to results release
improve efficiency

Laboratories must have internal systems of governance and quality controls in place for:

staff training and competency (standard operating procedures)
the registration of requests and history checks at specimen reception
the parameters for determining which cases are eligible for auto-authorisation
processes to ensure results transferred from the testing platform have passed quality control steps
the transfer of results to the laboratory information management system (LIMS) and the rigour of any algorithms
processes for the safe release of auto-authorised result queues from LIMS
manual interventions and management protocols
procedures for the prevention of the erroneous release of results
procedures for dealing with an erroneous release of results to the Cervical Screening Administration Service (CSAS)
routine audits for adopting the technique in terms of ISO accreditation
error logging and root cause analysis
responding to mismatches flagged by CSAS that act as a backstop failsafe
the route for addressing problems and their escalation (as necessary)

Laboratories are responsible for setting up, testing and validating the entire auto-authorisation process before it is used in the live environment. Evidence of systems validation is essential for laboratory accreditation (ISO 15189).

7.4 Compliance and assurance framework

The service provider works within a regulatory framework. Organisations such as the Medicines and Healthcare Products Regulatory Agency (MRHA) and the Care Quality Commission (CQC) are responsible for monitoring and certifying compliance at this level.

The United Kingdom Accreditation Service (UKAS) is the sole national accreditation body for the UK. Laboratories must have, or be registered for, accreditation to ISO 15189.

7.5 The laboratory infrastructure

Laboratories must have an infrastructure that provides an overview of all compliance assurance activity and identifies who within the department is responsible for each element. There must be agreement on processes and interactions which set clear expectations for effective working. Networked laboratory solutions in the context of cervical cytology screening services are not supported. All screening should take place at a single laboratory site.

Laboratories must ensure that:

a medically qualified consultant pathologist takes responsibility for the issue of all cervical screening test results
at least 2 medically qualified consultant pathologists who actively practise in cervical cytology are involved in the provision of an NHS CSP cervical screening service (while the programme recognises the RCPath view on clinical responsibility for cytology services, it does not align with the current programme standard or commissioning specification)
the consultant pathologists practise in cervical cytology at the laboratory where screening of cervical cytology samples is undertaken
there is cross cover so that one consultant pathologist is always on site and available to provide direction to staff, including consultant biomedical scientist
the consultants are fully integrated into the working of the department and present during normal laboratory opening hours for staff to consult with or vice versa

7.6 The roles and responsibilities of service leads

Service leads have specific responsibility for clinical governance and are directly accountable for the quality of their own work and that of their departmental teams. The entire screening pathway, including associated follow up services, must be functional and safe.

The role of the lead pathologist for cervical cytology triage

The lead pathologist for cervical cytology triage must:

be a consultant cellular pathologist registered on the GMC specialist register
have a nominated deputy who can be a medical pathologist or a consultant biomedical scientist
be employed in a laboratory which provides a cervical cytology service
report cervical cytology and satisfies NHSCSP standards in relation to cervical screening
undergo an annual appraisal which encompasses this lead role
have a job plan which takes account of this role and its time commitment
have satisfactory and appropriate participation in an appropriate CPD scheme (for example, RCPath) which must be discussed at appraisal
participate satisfactorily in the gynaecological cytopathology external quality assessment (EQA) scheme which must be discussed at appraisal
be in the department on a daily basis as far as practically possible (or, if not, the nominated deputy must be)
support assessing the overall quality of the cytology service including hrHPV testing
take overall responsibility for the quality of reports issued for the NHSCSP
make sure, with the lead scientist, that all laboratory staff are qualified for their roles
make sure, with the lead biomedical scientist and cellular cytology laboratory manager, that the laboratory follows all national guidance related to cervical screening
advise on the implementation of new guidance or monitoring of new standards as published by the NHSCSP, RCPath or BAC as appropriate
attend cervical screening multidisciplinary meetings, or make sure that a laboratory representative (other consultant or consultant biomedical scientist) is present – to discuss mismatches between histology and cytology and other appropriate cases
make sure that 100% of multidisciplinary team (MDT) meetings are attended by a suitably qualified person such as another medical consultant or consultant biomedical scientist
be responsible for making sure the necessary pathology input is made for cervical cancer reviews
advise and participate in audit for the local cervical screening programme
attend trust cervical screening business meetings, or make sure that a deputy is present where the performance of the service will be monitored and trust business issues discussed
attend relevant cervical screening programme board meetings (multidisciplinary) with area teams, or make sure that a deputy is present where the performance of the local service is monitored and local programme issues discussed
contribute where necessary to any quality reports given to the local trust cervical screening business meeting, area team meeting or trust governance meeting and contribute to any annual reports relating to the local service
sign off KC61 and other screening quality assurance service (SQAS) data returns and audits
be the primary medical contact within the department for cervical cytology triage matters

The role of the lead scientist for cervical cytology triage

The lead scientist for cervical cytology triage must:

be employed in a cytology laboratory which provides a cervical screening service to the NHS
be registered with the Health and Care Professions Council
be a consultant or senior biomedical scientist responsible for delivery of the cervical screening laboratory services
have a nominated deputy
undergo an annual appraisal which encompasses this lead role
participate satisfactorily in the gynaecological cytopathology external quality assessment (EQA) scheme, which must be discussed at appraisal
work collaboratively with the medical consultants, consultant scientists, laboratory managers and the CSPL to monitor and maintain high quality laboratory services
have experience of leading a clinical laboratory service
oversee the development and review of laboratory policies and procedures
make sure the laboratory follows NHSCSP guidance in relation to all aspects of cervical screening
support the implementation of new guidance or monitoring of new standards as published by the NHSCSP, RCPath or other relevant bodies as appropriate
make sure all scientific and laboratory support staff have the appropriate qualifications, training and registration where appropriate
make sure the competence of all laboratory staff is monitored, maintained and evidenced
make sure all direct referral and failsafe mechanisms operate safely and effectively

The role of the lead virologist for hrHPV testing

The lead virologist must:

be a consultant virologist (medical or clinical scientist)
be registered with the General Medical Council (GMC) or Health and Care Professions Council (HCPC)
be employed in a laboratory which provides an accredited hrHPV testing service
link with the cytology laboratory service to make sure hrHPV testing protocols are provided to NHSCSP standards or recommendations
undergo an annual appraisal which encompasses this lead role
have a job plan which takes account of this role and its time commitment
have satisfactory participation in the CPD scheme for their professional body which must be discussed at appraisal
advise the cytology laboratory to make sure it follows NHSCSP guidance for clinical hrHPV testing and national guidance related to nucleic acid amplification assays
advise the lead hrHPV scientist on participation in an ISO accredited national EQA scheme for hrHPV testing, internal quality control monitoring and internal quality assurance procedures
advise on compliance with NHSCSP criteria for the assessment and implementation of new or modified techniques relevant to the hrHPV service
have a nominated deputy
be available for advice on a daily basis, or make sure there is support from the deputy
advise on the implementation of new guidance or monitoring of new standards as published by the NHSCSP, RCPath or other relevant bodies
attend cervical screening multidisciplinary management meetings where appropriate, or make sure a deputy provides cover
advise on audit for the local cervical screening programme relevant to the role in the programme
attend senior management meetings, or make sure that a deputy is present where the performance of the service will be monitored and service issues discussed
receive minutes of the multidisciplinary programme board meetings, where the performance of the local service is monitored and local programme issues discussed
contribute where necessary to any quality reports given to the local trust cervical screening business meeting, area team meeting or trust governance meeting and contribute to any annual reports relating to the local service
be the primary contact within the department for hrHPV clinical matters

The role of the lead scientist for hrHPV testing

The lead scientist must:

be employed in a cytology or virology laboratory which provides an accredited hrHPV testing service – these laboratories must be co-located
be a senior member of staff responsible for delivery of the hrHPV testing service
support all aspects of delivery of the hrHPV service
be registered with the Health and Care Professions Council (HCPC)
have experience of leading and troubleshooting a high-throughput molecular diagnostic service
provide an hrHPV testing service in line with ISO 15189
be responsible for making sure that the laboratory follows NHSCSP guidance for clinical hrHPV testing and national guidance related to nucleic acid amplification assays
support the implementation of new guidance or monitoring of new standards as published by the NHSCSP, RCPath or other relevant bodies as appropriate
make sure there is compliance with NHSCSP criteria for the assessment and implementation of new or modified techniques relevant to the HPV service
provide molecular diagnostics training and support
make sure the competence of molecular laboratory staff is maintained and evidenced

7.7 Service level agreement (SLA) for virology services

Cervical cytology laboratories must have an SLA(s) in place for virology services. This can vary depending on where the hrHPV test is carried out, whether within the cytology department or a virology department. The cytology and virology leads must set clear expectations for collaborative working and agree processes and interactions to demonstrate regular engagement for the duration of the contract.

SLA for consultant virology support within the cytology department

A cytology service undertaking hrHPV testing must have appropriate consultant virologist support, and be documented in an SLA. The SLA should make sure that virology support is available to the cytology service when required.

SLA for hrHPV testing performed in a virology department

There must be an SLA between the cytology department and the virology department to specify the services required. The cytology and virology departments can be in different organisations but must be co-located on the same site, and this must be defined in the SLA.

As a minimum, the SLA must specify:

which organisations or departments the agreement is between
the time period for the service
the expected level of activity
the arrangements for modifications to the agreement
the service being provided
the arrangements for providing test consumables
the cost of the service
the payment terms
the legal issues – for example penalty clauses for underperforming
the requirement for the laboratory to be accredited to ISO 15189
requirement to notify the cytology service of any change to its accreditation status
which hrHPV testing platform is being used
the transport of samples to virology
how samples will be tested
that IQC and QA must be carried out in accordance with national guidance
how final results will be authorised and provided to cytology
the expected turnaround time of samples for hrHPV testing to make sure there is compliance with the overall 14 day turnaround standard
the steps involved in the specimen pathway and areas of responsibility for cytology and virology (a flow diagram must be provided)
the business continuity planning for the hrHPV testing service
the arrangements for NHS confidentiality training
the arrangements for health and safety
the compliance with staff training and competency assessments
the requirements to provide performance data to the SQAS and the local cervical screening business meeting
the requirements to attend meetings to discuss performance or any service issues or changes

Honorary contract for service advisers

A consultant virologist or lead scientist appointed to provide external advisory services to a cytology laboratory must hold an honorary contract with the host provider.

As a minimum the contract must state the:

contracting organisation as a legal entity
professional registration requirements
duties of the contracted appointee
reporting and accountability arrangements
arrangements for appraisal and performance development
arrangements for any performance requirements

7.8 Role of the cervical screening provider lead

All organisations that provide NHS cervical screening services must have a cervical screening provider lead (formerly called a hospital-based programme coordinator). The cervical screening provider lead’s (CSPL) role will vary depending on what services or combination of services are provided at the relevant site.

The services provided can be NHS, private or standalone for:

cervical cytology triage
hrHPV testing
cervical histology
colposcopy

7.9 Outsourcing laboratory services

The service provider must make sure that the:

laboratory meets the required standards of the NHSCSP as set out in the national service specification and professional guidance documents
description of the service to be provided, quality standards and contract/service management arrangements are included in a contract and/or service level agreement

The service provider is responsible for enabling locum staff to:

meet the requirements and standards of the NHSCSP
meet the training and update requirements of the NHSCSP
routinely participate in the gynaecological cytopathology EQA scheme

The service provider is responsible for making sure these requirements are included in a contract or service level agreement.

7.10 Programme standards and performance monitoring

National programme standards

The national programme standards define a set of measures that providers must meet to make sure local programmes are safe and effective. The standards enable assessment of the screening process and support continuous improvement.

Performance data

SQAS routinely collects laboratory data that are analysed to allow comparisons against the national standards and other quality indicators. SQAS feeds back this data to laboratories and commissioners. This approach, amongst others, helps SQAS to assess and quality assure cervical screening laboratories.

Data collection following primary hrHPV screening implementation

SQAS specifies the data for collection and submission by laboratories. It specifies the method of data collection and the frequency of submission to make sure it is consistent and allows comparisons with the pilot sites.

Data are carefully analysed prior to the introduction of any new performance measurements or new standards.

Key performance indicators (KPIs)

Screening KPIs are contained within both the Section 7a agreements between the DHSC and NHS England and in the Public Health Outcomes Framework (PHOF).

KPIs are a subset of programme standards that are collated and reported quarterly. NHSCSP produces regular KPI reports for the provider of the screening programme and NHS England to monitor and evidence adherence to the screening pathway.

Laboratory performance indicators

The laboratory performance indicators provide measures that enable the programme to operate at an optimal ratio of maximum benefit to minimum harm.

The performance indicators are routinely calculated from the laboratory KC61 and other SQAS data returns. Some are influenced by the whole service which includes cytology, colposcopy, and histology. Performance indicators must be calculated by the laboratories themselves. The identification of outliers requires analysis of the routine data returns which are aggregated and reported centrally.

Performance measures

Performance measures work on the principle of investigating those laboratories with a performance that falls outside a set range or below an expected value. These measures must be continuously monitored by the laboratory. Failure to meet them must always trigger further investigation and result in appropriate action taken when necessary.

Laboratories must have systems in place where the data are regularly reviewed at departmental meetings, CSPL management meetings and laboratory/trust governance meetings.

Laboratories whose performance falls outside the indicated ranges must, with the assistance of their quality assurance team, investigate and provide evidence to support an explanation for this performance. This explanation might not necessarily be related to reporting practice. Required adjustments to reporting practice must be undertaken immediately.

Performance outside the indicated range might be due to inadequate or inaccurate statistical information. Examine this and correct where necessary. It should be recognised that performance within the ranges identified does not guarantee satisfactory performance.

Reporting profiles

Calculate the percentage of cytology samples reported by cytology classification for individuals and for the overall laboratory. Although these can vary and can only be useful where the workload case mix is the same, they provide comparative data which can be useful in detecting outliers.

Cytology inadequate rates

This is the number of cytology samples classified as inadequate (which were hrHPV positive initially) expressed as a percentage of all cytology samples.

The sensitivity of cervical cytology is based on the requirement of cytology screeners to classify cytology samples as normal (including inadequate) or abnormal. It is important to monitor inadequate rates.

Sensitivity of cytology screening

You must calculate cytology sensitivities for individuals and for the overall laboratory. These are calculated from samples initially classified as inadequate, negative or abnormal at the first full cytological examination when compared to the final report. False negative cases are identified through rapid review or preview. Each member of staff’s independent opinion must be recorded to enable correct calculation.

The expected cytology sensitivities are:

high grade: more than 95%
all abnormal: more than 90%

We will review the standards once we have collected and analysed sufficient data.

The programme standards illustrate the calculation for the sensitivity of cytology screening based on rapid review or preview to minimise false negative cervical screening test reporting.

Positive predictive value (PPV) for CIN2 or worse

PPV is a measure of the laboratory’s or individual’s ability to predict CIN2 or worse from cytology with results of high grade dyskaryosis (moderate) or worse.

Following primary hrHPV testing implementation PPVs must also be calculated per colposcopy clinic.

We recognise that PPV can be influenced by progression or regression of the lesion in the period between cytology and histology. Biopsy samples may not be representative of the lesion, and the histological result is subject to observer variation.

The outcome of a negative test may be unknown for several years after taking the cervical sample, by which time lesions on the cervix may have developed de novo, progressed or regressed. Predictive value gives a measure of the specificity of a laboratory/individual but not the sensitivity.

Abnormal predictive value (APV) for CIN2 or worse

APV calculates the percentage of samples reported by an individual or laboratory as low grade dyskaryosis or borderline that led to referral with a subsequent histological diagnosis of CIN2 or worse but excluding non-cervical neoplasia.

The expected range is calculated from the fifth to the 95th percentile from the previous year’s KC61 return.

Similar factors that influence the PPV can also influence the APV. Following primary hrHPV testing implementation APVs must also be calculated per colposcopy clinic.

Referral value (RV) for CIN2 or worse

The Referral Value (RV) is defined as the number of women referred to colposcopy (excluding inadequate referrals) per detection of one CIN2 or worse lesion but excluding cases reported as ?glandular neoplasia (non-cervical).

As for the PPV, it is also a measure of the accuracy of prediction of CIN2 or worse with low RV indicating good prediction and high RV indicating possibly overcalling. It will be influenced by similar factors to PPV and APV.

The expected range is calculated from the 5th to the 95th percentile from the previous year’s KC61 return.

Performance ranges

The table below describes the performance ranges.

Table 3: performance ranges

Note that cases reported as ?glandular neoplasia (non-cervical) are excluded from PPV, APV and RV calculations. Also, for PPV cases not having CIN2 or worse include where no abnormality is detected on colposcopy.

Criterion	Performance indicator	Range/Value
Inadequate cytology sample reports	Number of inadequate samples expressed as a percentage of all cytology samples	5th to 95th percentile
Cytology sensitivity – all abnormals	Percentage of samples correctly called abnormal taking into account those identified at rapid review	more than 90%
Cytology sensitivity – high grade abnormals	Percentage of high grade samples that were correctly called abnormal, taking into account those identified at rapid review	more than 95%
PPV for CIN2 or worse	Percentage of women referred with high grade cytology or worse whose biopsy is reported as CIN2 or worse	5th to 95th percentile
APV	Percentage of women reported as low-grade dyskaryosis who have high grade abnormalities on histology	5th to 95th percentile
RV	Number of women referred to colposcopy to detect one CIN2 or worse lesion	5th to 95th percentile

Performance ranges will need to be reviewed when a smaller number of laboratories are undertaking primary hrHPV testing.

7.11 Quality assurance

Screening quality assurance (QA) is the process of checking that programme standards are met and encouraging continuous improvement, to make sure that all women have access to high quality screening wherever they live. QA is essential to minimise harm and maximise benefits of screening.

The programme specific operating model (PSOM) for QA of the NHSCSP outlines the process for a consistent approach across all screening providers.

SQAS undertakes a number of activities to assure and improve the quality of screening services. Cervical screening laboratories must be fully compliant with the PSOM and co-operate fully with QA activities.

7.12 Quality improvement

Quality improvement makes local programmes safe, effective, patient-centred, timely, efficient and equitable. A quality improvement culture is an integral component of the governance and performance management processes for the screening care pathway for women.

Audit of quality systems

UKAS accredits a laboratory’s quality system through internal and external audit in compliance with standard ISO 15189. Audit is integral to continual improvement of the quality system and all laboratory staff must participate in the departmental annual audit programme.

Audit of invasive cervical cancers

Laboratories must comply with the requirements of the national audit of invasive cervical cancers and, where appropriate, the requirements of the programme guidance on duty of candour.

Additional audits

We recommend that laboratories carry out additional audits in accordance with departmental annual plans.

We also recommend giving priority to a review of the previous negative cytology in women who have had 2 positive tests for HPV 12 months apart, and who have been referred for colposcopy with a histological outcome of CIN2 or worse. The cytology review should reveal whether they were true false negatives or whether abnormal cells were present and not identified originally.

External quality assessment

EQA is a process for checking the quality of a service or an individual’s performance by an external body. Laboratories must participate in the relevant accredited interpretive and technical national EQA schemes.

There are 2 compulsory EQA schemes.

Gynaecological cytopathology EQA scheme

All individuals reporting cervical cytology must participate in and demonstrate acceptable performance in the gynaecological cytopathology EQA scheme. The scheme evaluates interpretive skills.

Technical EQA scheme

All laboratories providing a cervical cytology triage service must participate in and demonstrate acceptable performance in the technical EQA scheme. The scheme evaluates the laboratories’ quality of specimen preparation and staining.

Laboratories must also participate in an ISO accredited EQA scheme for HPV testing in line with programme guidance. Laboratories must demonstrate acceptable performance in the scheme.

7.13 Risk and incident management

In all services and programmes errors can, and will, happen. Some errors will be relatively minor but others can be serious. The national guidance for managing safety concerns, safety incidents and serious incidents in NHS screening programmes provides clarity for staff providing and commissioning NHS funded services who may be involved in identifying or managing a screening incident.

Programmes should use the failsafe processes to assist risk management and avoid or manage incidents effectively. This should complement local risk management strategies and processes.

Laboratory failsafe

Failsafe is a back-up mechanism which makes sure that if something goes wrong in the screening pathway then processes are in place to identify what that is and what action should follow to make sure there is a safe outcome.

Laboratory failsafe is through the correlation of histology and colposcopy reports and failsafe reminder letters to GPs and sample takers. The known outcome can include information recording those refusing treatment or persistently defaulting from appointments.

7.14 Business planning and continuity

The laboratory service must have a contingency plan in place to make sure there is resilience and continuity of service when faced with disruptive events such as equipment failure and down time, prolonged loss of power or IT systems or flood or fire damage to the laboratory.

There must be a formal record which identifies:

the main risks
how the main risks can be mitigated
how the laboratory would recover from a major incident or fault

Contingency plans must include intra-laboratory planning such as failure of crucial equipment and inter-laboratory planning where a service or part of a service can require work to be transferred to another laboratory site.

Carry out a risk analysis of laboratory processing to identify crucial equipment and describe how the service would recover from prolonged down time. This can involve duplication of crucial equipment (for example, HPV platforms) or high-level service contracts with short response times to repair failed equipment. Protect critical equipment with an uninterruptable power source (UPS).

If middleware is used to link the LIMS to HPV platforms or the call and recall system, there must be an agreement in place for rapid (preferably remote access) recovery of the link in the event of failure.

Test all contingency plans to make sure that in the event of putting them into practice, the steps described will result in service recovery. Record the testing process and outcome.

Failure of IT systems may require reverting to a short term manual process to record sample details. Store manual ‘day sheets’ for recording sample details along with the standard operating procedure (SOP) for their use in a clearly labelled location to allow the move to manual processes in the event of IT failure.

Identify individuals with service critical skill sets and put systems in place to make sure there is continuity of service in event of their prolonged absence. Consider having named deputies for important roles.

Regularly test data back-up tested by restoring the previously backed up data.

All agreements with external agencies to maintain service resilience must be clearly described in a formal document such as an SLA or memorandum of understanding (MoU). Formal agreements must clearly identify individual responsibilities. All agreements must meet the ISO 15189 standard and only laboratories that meet the ISO standard and standards set by PHE can be used for resilience planning.

Question 8

8. Laboratory organisation

Accepted Answer

The following information provides guidance and new recommendations to help laboratory managers make the best use of the resources at their disposal, and make sure that local working practices adhere to the guidance in this document.

8.1 Staffing requirements for primary hrHPV testing

We will update this document when the laboratory staffing requirements for primary hrHPV testing are fully established.

8.2 Staffing requirements for cytology triage

Calculation of staffing levels and working periods

The following calculation determines the staffing requirements for cytology triage:

5 hours in attendance for the NHSCSP at ‘A’ slides per attendance hour * ‘A’ was previously regarded as 5 for conventional cytology but there is evidence of increased productivity with LBC samples^{[footnote 9]} ^{[footnote 10]} ^{[footnote 11]} * laboratories will need to assess their own average productivity rate before using this calculation Output per screener per day = 5 x A slides = B Number of screening days per annum = Number of days worked per week x number of weeks worked per annum = 5 x 44 = 220 * 44 weeks takes into account annual leave, study leave and average sick leave Maximum number of slides screened per screener per year = B x 220 = D Minimum number of screeners required = Laboratory annual workload/D Maximum number of screeners allowed = Laboratory annual workload/3000 * 3000 is the minimum number of cytology samples that must be screened annually by a screener

8.3 Organisation of workload

Minimum workload numbers

Those undertaking the first cytological examination of a cervical cytology slide must screen a minimum of 3,000 samples per annum. This minimum number is unrelated to working hours. Working patterns must be suitable to enable this minimum workload to be achieved.

Screening throughput

Calculate the mean throughput of cervical cytology triage slides from a laboratory over any representative period and include all other NHSCSP duties and breaks. Throughput per hour is known as the rate per hour. This is calculated as the mean number of slides initially examined cytologically per hour by an individual screener or group of screeners when all other NHSCSP duties are included.

Working period for cytology triage

Maintain a safe working period (the hours of attendance at work in a 24-hour day) to optimise the performance of cytology screeners.

Note that:

screeners can safely and effectively undertake initial cytological assessments of cervical cytology slides for 4 hours in a normal working day – this can be up to 5 hours microscopy in total including rapid review/preview
the working period should be organised such that a break in continuous screening should be of at least 20 minutes duration and ideally should be taken away from the screening room – this break should be taken after no more than 2 hours at the microscope.
regular micro-breaks of several seconds should be taken every 10 to 15 minutes
the other duties required of cervical cytology screeners can act as breaks from microscopy

Non-microscope duties both within and outside the screening programme can account for additional hours worked per day.

A working day of 5 to 6 hours allows for up to 4 hours of cytology triage, rapid review and, or preview, natural breaks and other duties to be carried out.

Fatigue and discomfort increase over time so we consider it is good practice that the above time periods should apply to each 24-hour period.

Managers must be vigilant in their application of these working arrangements and in the monitoring of individual and laboratory performance. Managers should also be alert to the ergonomic aspects of microscopy work and to screener self-reporting of fatigue.

Rates of working

The screener rate of working varies hour by hour, screener by screener and slide by slide. This variation is to be expected as the complexity of the slides being screened varies and the performance of the screener changes over time. The other duties expected of screeners will also determine how many slides are screened over a given period as will the recommendation requiring that screeners screen a minimum of 3,000 slides per annum for skill maintenance.

8.4 Staff roles and responsibilities

The role of the cervical cytology screener

A cervical cytology screener is a trained individual employed to undertake the initial cytological examination, double screening and rapid screening of cervical cytology samples. These individuals must have successfully completed the NHSCSP training programme syllabus that includes an external assessment sat under examination conditions, or one of its predecessors (the City & Guilds Level 3 Diploma in Cervical Cytology, the NHSCSP Certificate in Cervical Cytology, or the former BSCC or IBMS certificate of competence in cervical screening).

The initial cytological examination is a full screen of a cervical cytology sample following a positive hrHPV test. A full screen is the systematic examination of the entire cervical cytology sample, which is all the material on the slide using a minimum 100 x magnification and overlapping sweeps. A qualified screener can sign out and report negative or inadequate cytology samples that are positive for hrHPV and that have undergone an initial screen and quality control procedures (rapid preview/review).

We recognise that other duties are required of cervical cytology screeners. These include:

quality assurance and quality control procedures
receipt of specimens
slide preparation
data entry

The role of the biomedical scientist

Biomedical scientists have varied roles and responsibilities within the cervical screening laboratory. All biomedical scientists who perform microscopy-based duties must hold an appropriate screening qualification as a minimum. As well as undertaking initial cytological examination of slides, a biomedical scientist can, depending on their experience and qualifications, perform a second examination of a slide initially deemed potentially abnormal (checking) and reporting of abnormal cytology samples.

Biomedical scientists holding the Advanced Specialist Diploma (ASD) in Cervical Cytology must report or review a minimum of 750 slides per year. Biomedical scientists can also perform supervisory, training and management roles within the laboratory.

8.5 Laboratory internal quality control of cytology triage

Internal quality control is an essential component of laboratory quality assurance undertaken by the use of rapid review ^{[footnote 12]} or rapid preview of cytology samples.

Rapid review

Rapid review ^{[footnote 12]} is one of the approved methods for routine quality control of cervical cytology. It is a swift re-examination of all cervical cytology samples identified as negative or inadequate at the initial cytological examination, as part of the quality control process. The cytology samples are not fully screened.

Rapid review is still relevant as a quality control method for cytology slides examined after a positive primary HPV test. It must be used when cervical cytology samples have been evaluated as negative or inadequate after a positive primary HPV test.

Note that:

rapid review must only be carried out by qualified members of staff who are meeting competency standards
the rapid reviewer must be a different individual from the person undertaking the initial examination
individuals must undergo training in rapid review prior to undertaking this activity and show competency in this technique
a rapid review must take at least 60 seconds
if a discrepancy is identified during rapid review then this must be recorded and passed to a staff member responsible for checking
laboratories should record rapid review data to allow for individual screening numbers and sensitivities to be calculated
individuals should not rapid review more slides than they normally primary examine in a day
the method of rapid review must be regularly audited within the laboratory to validate its effectiveness

Rapid preview

Rapid preview is an alternative approved method for routine quality control in cervical cytology. It is also still relevant as a quality control method for cytology that is examined after a positive primary HPV test. Rapid preview is performed in exactly the same way as rapid review and is undertaken prior to the initial full cytological examination of the slide. All cytology slides are subject to rapid preview not just those classified as negative or inadequate. The cytology samples are not fully screened.

The important advantages to this method are that:

as all the abnormal samples are still present the previewer does not have a ‘high expectation of negative’ as in rapid review (when approximately 90% of the abnormal samples have been identified and removed) – this lower expectation of negative means the previewer is less likely to miss the abnormality when it is present
the initial cytology examination findings (following rapid preview) can be used as a quality control tool for the rapid preview process – this allows allowing sensitivity calculations and performance assessments to be made

There are no national quality standards for performance in rapid preview. Poor performance can only be identified through peer comparison.

The choice of which quality control method used should be a management decision based on the balance of the fewer resources needed to undertake rapid review and the potential benefits in quality allowed by the advantages of rapid preview.

8.6 Information for sample takers

Laboratories have a role in providing information to sample takers on the quality of their samples, for example, the proportion of rejected and the reasons for that assessment. Feedback to novice sample takers as well as existing sample takers can be valuable, especially if an issue is identified.

Laboratories also play a vital role in the general education of sample takers as a whole and are often the first port of call for screening programme-related enquiries, or well placed to identify who can assist.

8.7 Novice sample takers

There must be provision for training sample takers in areas and practices that have converted to primary HPV screening.

Cervical screening laboratories no longer make cytology preparations from samples taken by novice sample takers (since 1 March 2020), nor do they provide feedback on transformation zone (TZ) sampling.

The presence of transformation zone (TZ) cells is not a requirement for assessment of adequacy in cervical screening samples. The cellularity of the cytology samples for novices is assessed in exactly the same way as for non-novice samples and does not require TZ cells to be present. The adequacy data of these samples forms part of the novice sample takers assessment.

Please note we are reviewing the assessment criteria for training novice sample takers and the outcome of the review will update this guidance in due course.

All samples taken by novice sample takers must be clearly identified to the laboratory. Samples which give an unreliable hrHPV result must be repeated after a period of no less than 3 months. For the purposes of sample taker training they are recorded as unsatisfactory.

All cytology and hrHPV test results must be logged on the laboratory IT system to give a full record of the test result, and so that feedback can be given to both trainee sample takers and course organisers in the usual way.

Management of women and the transfer of screening results to the call and recall IT system must follow recognised screening protocols.

8.8 Multidisciplinary working in the NHSCSP

The laboratory must have an SOP to describe the entire MDT process. Laboratories must have procedures in place to cover the whole MDT process from case selection through to further patient management. Log all cases that are discussed. Document clear records of the outcomes in the patient notes either in writing or using an MDT record sheet.

Clearly document the results of reviews of samples for MDT purposes on MDT records along with the details of who carried out the review

Take into account the hrHPV status, cytological, histological and colposcopic evidence to make sure there is appropriate patient management. For the majority of women in the screening programme, this involves relatively straightforward referral and management protocols. However the MDT approach to patient management is particularly important where a woman may require referral for treatment of glandular and/or invasive disease.

The MDT approach is also valuable in reviewing women with discrepant cytology, histology and or colposcopy outcomes. Conduct periodic audits to make sure that all relevant cases have been included.

Note that the laboratory does not reissue cytology reports as a result of an MDT review.

8.9 Health and safety regulations

Laboratories must comply with the Health and Safety (Display Screen Equipment) Regulations 1992. The regulations also advise on breaks and the organisation of work.

8.10 Ergonomic working standards

Laboratories must comply with the NHSCSP ergonomic working standards.

Acknowledgements

Members of the CPG for Laboratories (past and present):

Mr Steve Court, Dr Paul Cross, Mr John Crossley, Dr Karin Denton, Dr Steve Ferryman, Dr Thomas E Giles, Dr Mark Hopkins, Ms Carina Hume, Ms Jackie Jamieson, Ms Lyn Jenkins, Dr David Nuttall, Ms Philippa Pearmain, Mrs Janet Rimmer, Dr Alex Sargent, Dr John H F Smith, Mrs Ruth Stubbs, Mrs Sharon Whitehurst, Mr Allan Wilson

Special thanks to Dr Steve Ferryman for all his hard work and generous support in the development of this guidance.

References

Slater DN, Rice S, Stewart R, and others. Proposed Sheffield quantitative criteria in cervical cytology to assist the diagnosis and grading of squamous intra-epithelial lesions, as the British Society for Clinical Cytology definitions require amendment. Cytopathology, 2005, 16: 179 to 192 ↩ ↩²
Denton K, Herbert A, Turnbull L, and others. The revised BSCC terminology for cervical cytology. Cytopathology, 2008, 19: 137-157. 10. ↩ ↩² ↩³ ↩⁴
Palmer T, Nicoll S, McKean M, Park A, Bishop D, Baker L and Imrie J. Prospective parallel randomized trial of the MultiCyte™ ThinPrep® imaging system: the Scottish experience. Cytopathology 2013;24: 235 to 245 ↩
Waddell C. Glandular neoplasms of the uterine cervix. In: Diagnostic Cytopathology. Gray W, McKee G (eds). Edinburgh; Churchill Livingstone; 2003: pp. 791 to 812 ↩
Psammoma bodies in cervical smears: sifting the grains of sand Smith JHF Cytopathology 2007; 18: 140 to 142 ↩
Colposcopy and Programme Management. Guidelines for the NHSCSP (NHSCSP Publication No 20). Second edition. Sheffield, NHS Cancer Screening Programmes, 2010. ↩
Nayar R and Wilbur D C. The Pap Test and Bethesda 2014. Acta Cytologica 2015;59:121 to 132. DOI: 10.1159/000381842 ↩
Dowie R, Stoykova B, Crawford D and others. Liquid-based cytology can improve efficiency of cervical smear readers: evidence from timing surveys in two NHS cytology laboratories. Cytopathology 2006;17:65 to 72 ↩
Doyle B, O’Farrell C, Mahoney E, Turner L, Magee D, Gibbons D. Liquid-based cytology improves productivity in cervical cytology screening. Cytopathology 2006;17: 60 to 4. ↩
Williams, ARW. Liquid-based cytology and conventional smears compared over two 12-month periods. Cytopathology 2006;17: 82 to 5. ↩
Dudding N, Hewer E, Lancucki L. Rapid screening: a comparative study. Cytopathology 2001; 12: 235 to 248 ↩ ↩²

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1. Primary hrHPV testing

1.1 Acceptable cervical samples

1.2 HPV test unavailable (infection code U)

1.3 Negative hrHPV test (infection code Ø)

1.4 Positive hrHPV test (infection code 9)

2. Reporting hrHPV tests and use of HPV unavailable (HPV-U) category

2.1 Sample internal control (endogenous): definition

2.2 Test run control (exogenous): definition

2.3 Sample internal control not detected

2.4 Failed samples note

2.5 SurePath samples with broom head missing or ThinPrep samples with broom head present

2.6 Out of programme samples and major labelling discrepancies

2.7 Cervix not visualised and, or no 5 x 360 degree sweep

2.8 Samples received in out-of-date vials or vials expired before testing

2.9 Samples beyond the recommended or approved storage time for an hrHPV test, and within vial expiry date

2.10 Sample vials that have leaked

2.11 Samples contaminated with blood and/or mucus

3. Cervical cytology samples

3.1 Cervical cytology sample: definition

3.2 Vaginal vault sample: definition

3.3 BD focal point slide profiler

3.4 Adequacy of cervical cytology samples

3.5 Cell counting methodology

4. Reporting and classification of cervical cytology

4.1 Cytology classification and reporting codes

Table 1: List of cytology classification and cytology reporting codes

4.2 Inadequate for cytology triage (result code 1)

4.3 Cytology negative (result code 2)

4.4 Dyskaryosis

4.5 Grading squamous dyskaryosis

Low grade dyskaryosis (result code 3)

High grade dyskaryosis (moderate) (result code 7)

High grade dyskaryosis (severe) (result code 4)

4.6 Difficulties in grading dyskaryosis

4.7 Difficulties in the identification of dyskaryosis

Scanty abnormal cells

Hyperchromatic crowded cell groups (HCCGs)

Pale cell dyskaryosis

Bland dyskaryosis

Small cell severe dyskaryosis

4.8 High grade dyskaryosis/?invasive squamous cell carcinoma (result code 5)

4.9 ?Glandular neoplasia of endocervical type (result code 6)

4.10 Differentiating high grade squamous dyskaryosis and glandular neoplasia

4.11 ?Glandular neoplasia (non-cervical) (result code Ø)

Difficulties in the identification of non-cervical glandular neoplasia

4.12 Borderline change in squamous cells (result code 8)

Difficulties in the identification of borderline change in squamous cells

4.13 Borderline change in endocervical cells (result code 9)

Difficulties in the diagnosis of borderline change in endocervical cells

4.14 Reporting of borderline change in HPV positive samples

4.15 Reporting multiple diagnoses

Cervical abnormalities with co-existing non-cervical glandular neoplasia

Women with 2 cervices

4.16 Benign endometrial cells in cervical samples

5. Management of women

5.1 Women with negative hrHPV tests

5.2 Women with positive hrHPV tests

Repeat test at 12 months for women with hrHPV and negative cytology

Repeat test at 24 months for women with hrHPV persistence and negative cytology

?Glandular neoplasia (non-cervical)

5.3 Samples without a valid screening result

5.4 Follow up of women who have attended colposcopy

Women in follow up when primary hrHPV testing protocols are implemented

Women who have completed follow up

Follow up of untreated CIN1

Follow up of untreated CIN2

Follow up of treated CIN of any grade

Follow up of treated CGIN or SMILE

Follow up of incomplete excision of CGIN or SMILE

Follow up of cervical cancer

Vaginal vault samples

6. HPV and cytology result and action codes

6.1 HPV result codes

6.2 Cytology result codes

6.3 Action codes

6.4 Valid code combinations

Table 2: valid code combinations

7. Clinical governance

7.1 Commissioning arrangements