Cervical cytology/histology discrepancy: a 4‐year review of patient outcome

E. L. Moss, A. Moran, G. Douce, J. Parkes, R. W. Todd and C. E. W. Redman Cervical cytology/histology discrepancy: a 4‐year review of patient outcome Objective: To investigate the diagnosis, review and management of women identified as having a cytology/histology discrepancy. Methods: A review of all patients diagnosed with a discrepancy between referral smear and cervical histology was performed between January 2003 and December 2004. Cases were followed for a minimum of 4 years and patient management and outcome reviewed. Results: A significant discrepancy was identified in 79 cases, 0.1% of all smears (n = 80 926) analysed during the study period. A discrepancy between cytology and histology, obtained from large loop excision of the transformation zone (LLETZ), was confirmed by multidisciplinary review in 42 cases (53.2%). In 37 cases (46.8%) the cytological and/or histological diagnosis was revised; the cytology was significantly more likely than the histology to be amended (chi square P = 0.005), most often because cytology had been overcalled. Of the confirmed discrepancy cases, 33 (78.6%) were due to high‐grade squamous cell or glandular abnormalities on cytology with a negative, inflammatory or human papillomavirus (HPV) infection on histology (HGC/NH). HGC/NH cases were managed by cytological follow‐up in 29 (87.9%), of which 72.4% of the smears were negative when performed at least 6 months post‐excision. During the 4‐year follow‐up period six women with a confirmed HGC/NH underwent a repeat cervical excision (hysterectomy or LLETZ), and of these, HPV effect was seen in two cases but no cervical intraepithelial neoplasia was detected in any of the histological specimens. Conclusion: Cytology overcall was responsible for the majority of cytology/histology discrepancies. A confirmed discrepancy is not an indication for a further excisional biopsy but follow‐up is essential because a small percentage of patients may have disease that has been missed.     

An audit of cervical cytology in HIV‐positive women

O. E. O. Hotonu, J. Hussey, M. S. T. Basta, V. Wadehra, P. Cross and M. L. Schmid
An audit of cervical cytology in HIV‐positive women Objective: To investigate whether a cohort of human immunodeficiency virus‐positive (HIV+) women were having annual cervical cytology as recommended by the English National Health Service cervical screening programme (NHSCSP) guidelines. Methods: An audit of cervical cytology in an HIV+ cohort of 187 women by obtaining their last cervical cytology result and recall from local cytology services. Results: Of the 187 women in the audit, two were ineligible, leaving 185 women, 167 (90.3%) of whom were aged 25–64 years and eligible for screening. Of the 185 women, 126 (68.1%) had a cytology history, 50 (27%) had never had cervical cytology and nine (4.9%) had inadequate details to ascertain whether or not they had a cytology history. Of the 126 with a cytology record, 34 (27%) had a current cytological abnormality, which was low grade in 25 (19.8%) and high grade in nine (7.1%). Among women aged 25–64 years attending the clinic, these percentages were significantly higher than expected for England as a whole (P < 0.001). Of 126 women with a cytology record, 29 (23%) were overdue for their recall date and of these the previous test was abnormal in 14 (48.3%). Cytology tests were taken within the community setting in 61 (48.4%), whereas 65 (51.6%) were seen either at an HIV sexual health clinic or were under colposcopy follow‐up. Of 91 women with negative cytology only 50 (54.9%) were recommended for repeat in 12 months. Conclusion: This audit demonstrates a high rate of cytological abnormalities among HIV+ women compared with the screening population at large. Implementation of NHSCSP guidelines has been difficult and requires improved care pathways between HIV clinics, primary care and laboratories.     

Comparison of cytology and histology results in English cervical screening laboratories before and after liquid‐based cytology conversion: do the data provide evidence for a single category of high‐grade dyskaryosis?

R. G. Blanks and R. S. Kelly
Comparison of cytology and histology results in English cervical screening laboratories before and after liquid‐based cytology conversion: do the data provide evidence for a single category of high‐grade dyskaryosis? Objective: To determine whether the difference between the positive predictive value (PPV) for cervical intraepithelial neoplasia (CIN) grade 2 or worse (CIN2+) of referral from moderate dyskaryosis and from severe dyskaryosis was reduced after laboratories converted from conventional to liquid‐based cytology (LBC). Furthermore, to explore the cytology/histology agreement after LBC conversion, and to determine post‐LBC whether there was increased support for the use of one single category of high‐grade dyskaryosis (equivalent to high‐grade squamous intraepithelial lesion). Methods: The association between cytology and histology has been examined using annual Korner return data (KC61 returns) collected by laboratories from the English National Health Service cervical screening programme. The study compares return data before and after LBC conversion. Results: The study examined data from 102 laboratories that converted from conventional cytology to LBC. Before conversion the PPV for CIN2+ of severe dyskaryosis was 88% and after increased to 90% (P = 0.003). For moderate dyskaryosis the PPV for CIN2+ increased from 70% to 72% (P = 0.06). The absolute difference of 18% between severe and moderate dyskaryosis was therefore the same pre‐ and post‐LBC conversion. The PPV of mild dyskaryosis for CIN2+ before and after conversion reduced from 23% to 19% (P < 0.001). The agreement between cytology and histology measured using a weighted Kappa statistic increased from 0.52 to 0.60 after conversion to LBC because of small increases in the proportions of severe dyskaryosis or worse with CIN3+ outcomes and mild dyskaryosis with CIN1 or less outcomes. Conclusions: Following LBC conversion there was evidence of a modest increase in the agreement between cytology and histology but no evidence of a change in the absolute difference in PPV for CIN2+ between moderate and severe dyskaryosis. The data support the conclusion that women referred with moderate dyskaryosis will on average have a lower risk of progression to invasive cancer than women referred with severe dyskaryosis. If the data were considered to support the categories of high‐grade dyskaryosis (moderate) and high‐grade dyskaryosis (severe) before LBC conversion then it can be strongly argued that they also support these categories after conversion.     

Prevalence of high-risk human papillomavirus type 16/18 infection among women with normal cytology: risk factor analysis and implications for screening and prophylaxis

Objective: To determine the prevalence of high‐risk human papillomavirus (HR‐HPV) 16/18 infection of uterine cervix among women in the reproductive age group, with cytologically normal cervical (Pap) smears; to analyse the risk factors for HR‐HPV acquisition and to address their implications for cervical cancer screening and prophylaxis in a low resource setting. Methods: Cervical samples from 769 cytologically negative women (age 18–45 years) attending a tertiary care centre in Delhi were subjected to HPV DNA testing and HR‐HPV 16/18 and low‐risk (LR)‐HPV 6/11 sub‐typing by polymerase chain reaction. Univariate risk factor analysis was carried out in HR‐HPV positive (n = 86) versus HR‐HPV negative women (n = 683) by chi‐square test. Results: The overall HPV prevalence among cytologically normal women was 16.6%. HR‐HPV16 was detected in 10.1%, whereas HPV18 was detected in 1% of women. HR‐HPV 16/18 comprised 67% of the total HPV positives. There was no decline in HR‐HPV positivity with age, and women aged 40–44 years were at significantly increased risk for HR‐HPV prevalence (P = 0.03). Statistically significant associations of HR‐HPV infection were found with risk factors such as high parity (P = 0.04), cervicitis/hypertrophic cervix (P = 0.01), unhealthy cervix (P = 0.04), rural residence (P = 0.03), low socioeconomic status (P = 0.01) and illiteracy (P = 0.07). Conclusions: Although the sample size was small, based on the observation that HR‐HPV 16 and 18 contributed significantly to the overall HPV prevalence in our setting, we speculate that testing/prophylaxis for these prevalent high‐risk types could perhaps make cervical cancer screening and preventive programmes cost‐effective. Larger community‐based studies on HPV prevalence and persistence are required to validate these findings before definitive recommendations can be made to the policy makers.     

Cytology of the ‘penile’ neovagina in transsexual women

S. Weyers, K. Lambein, Y. Sturtewagen, H. Verstraelen, J. Gerris and M. Praet
Cytology of the ‘penile’ neovagina in transsexual women Objective: The primary objective was to describe the neovaginal cytology in transsexual patients (n = 50) treated with the inverted penile skin technique. Secondary objectives were to compare our cytological findings with patient characteristics including use of oestrogens, sexual orientation and penetrative intercourse. Methods: The medical and surgical history, sexual orientation and whether there was a current relationship were ascertained. A speculum examination was followed by microscopy of a Pap smear of the neovaginal vault. Results: Well‐preserved nucleated squamous cells were found in 72%. The correlation between their presence and sexual orientation was highly significant (P = 0.016), with those not sexually interested and homosexually oriented all having nucleated cells on the Pap smear. However, the correlation between these cells and penetrative intercourse failed to reach significance. Four samples showed atypical squamous cells of undetermined significance, all were negative for high‐risk human papillomavirus (HR‐HPV) types. One patient showed a low‐grade squamous intraepithelial lesion that was HR‐HPV positive. There was a significant correlation between the presence of cytological lesions and sexual orientation (P = 0.006). Four percentage of the specimens showed Döderlein bacilli. Inflammation was found in 30.6% of samples with squamous cells. Conclusions: The penile skin‐lined neovagina of transsexual women can reflect the cytological findings present in biological women. However ‘normal’ cervical cytology, with superficial, intermediate and parabasal cells as well as Döderlein bacilli, was found in only 4% of transsexual women. Although one patient’s Pap test showed koilocytes and was HR‐HPV positive, no high‐grade squamous intraepithelial lesions were identified.     

Diagnostic accuracy of liquid‐based endometrial cytology in the evaluation of endometrial pathology in postmenopausal women

C. Remondi, F. Sesti, E. Bonanno, A. Pietropolli and E. Piccione
Diagnostic accuracy of liquid‐based endometrial cytology cytology in the evaluation of endometrial pathology in postmenopausal women Objective: The aim of this study was to compare liquid‐based endometrial cytology with hysteroscopy and endometrial biopsy regarding its diagnostic accuracy in a series of postmenopausal women with abnormal uterine bleeding (AUB) or asymptomatic women with thickened endometrium assessed by transvaginal ultrasound as a screening procedure. Methods: Inclusion criteria were: menopausal status; the presence of AUB and/or thickened endometrium assessed by ultrasound (cut‐off 4 mm); a normal Papanicolaou (Pap) smear; and no adnexal pathology at ultrasound. Exclusion criteria were: previous endometrial pathology; and previous operative hysteroscopy. Of 768 postmenopausal women referred to our general gynaecology clinics, 121 fulfilled the inclusion criteria and were recruited to the trial. Twenty‐one refused to participate. Cytological sampling was carried out by brushing the uterine cavity using the Endoflower device with no cervical dilation and the vial was processed using a ThinPrep® 2000 automated slide processor. The slides were stained using a Pap method. Results: In 98 cases with histological biopsies, endometrial cytology detected five cases of endometrial carcinoma, 10 of atypical hyperplasia and 47 of non‐atypical hyperplasia; 36 cases were negative. In two cases cytology was inadequate because of uterine cervical stenosis. Taking atypical hyperplasia or worse as a positive test and outcome, the diagnostic accuracy of the endometrial cytology was 93.5%, with a sensitivity of 92% and specificity of 95%, a positive predictive value of 73% and a negative predictive value of 99%. All the carcinomas were detected by cytology. Only 42% of women with a positive diagnosis were symptomatic. The cytological sampling was well tolerated by all patients. No complication was registered. Conclusions: Liquid‐based endometrial cytology can be considered an useful diagnostic method in the detection of endometrial pathology as a first‐line approach, particularly if associated with transvaginal ultrasound.     

Factors contributing to false‐negative and potential false‐negative cytology reports in SurePath™ liquid‐based cervical cytology

N. Gupta, D. John, N. Dudding, J. Crossley and J. H. F. Smith
Factors contributing to false‐negative and potential false‐negative cytology reports in SurePath ? liquid‐based cervical cytology Objectives: The characteristics of false‐negative conventional cervical cytology smears have been well documented, but there is limited literature available for liquid‐based cytology (LBC), especially SurePath? samples. We aimed to assess the characteristics of false‐negative SurePath LBC samples. Methods: Over a period of 5 years, an audit of false‐negative reports in SurePath cervical cytology was undertaken. In a workload of 183, 112 samples, 481 (0.3%) false negatives were identified using two routes: those detected by routine laboratory internal quality control (rapid pre‐screening) (n = 463) and those reported as normal (true false negatives) with concurrent high‐grade cervical histology (n = 18). Ninety‐five false‐negative cases with a subsequent biopsy reported as at least cervical intraepithelial neoplasia grade 2 (CIN2+) were reviewed for a number of different cytomorphological features. Results: Of 95 samples with subsequent CIN2+, 30.5% predominately contained microbiopsies/hyperchromatic crowded cell groups (HCGs), 27.3% sparse dyskarytotic cells, 4.2% pale cell dyskaryosis, 6.3% small dyskaryotic cells; 3.2% were misinterpreted cells, 8.4% contained other distracting cells, 7.4% were low contrast, 5.3% were unexplained and 7.4% were true negatives. The mean number of microbiopsies/HCGs in that category was 4.6. The mean number of abnormal cells in the sparse dyskaryotic cell category was 13.8. Conclusions: Microbiopsies/HCGs were the commonest reason for false negatives. They were usually present in sufficient numbers to be detected but interpretation could be problematic. Dispersed single abnormal cells were usually not identified because of their scarcity or the presence of distracters.     

Review of negative and low‐grade cervical smears in women with invasive cervical cancer after the first 3 years of the national cervical screening programme in Slovenia

A. Repše‐Fokter, A. Pogačnik, V. Snoj, M. Primic‐Žakelj and M. S. Fležar
Review of negative and low‐grade cervical smears in women with invasive cervical cancer after the first 3 years of the national cervical screening programme in Slovenia Objective: The purpose of the study was to perform a national review of negative, low‐grade and inadequate smears reported during the latest screening period before cervical cancer diagnosis in 2006, after the first 3 years of the screening programme. Methods: Among 162 new cervical cancer cases there were 47 (29%) without previous cytology, 47 (29%) with one high‐grade smear prior to diagnosis and 68 (42.0%) with at least one previous negative, low‐grade, atypical or inadequate smear 1–40 months before diagnosis. Of the latter 68 cases, 37 patients with 59 smears (together with 118 control slides) were included in the review as 31 had smears reported at laboratories no longer operating. Findings were related to the last cytology report before diagnosis as well as to histological type and stage of the cancer. Results: In our study group, 19 (51%) of 37 patients had squamous cell carcinoma, 15 (41%) adenocarcinoma and 3 (8%) adenosquamous carcinoma, compared with 121 (75%), 26 (16%), 12 (7%), respectively, and 3 (2%) other types, for all carcinomas. Twenty‐one of 37 women also had high‐grade cytology prior to diagnosis of cancer. Women with previous cytology (with or without recent high‐grade smears) were more likely to have stage I cancers than those without cytology (P < 0.0001). The expert group upgraded 17/33 smears in the patients with squamous carcinomas, which was more than in those with adeno‐ and adenosquamous carcinomas (5/24, P < 0.05). Conclusion: As expected, a higher proportion of smears preceding adenocarcinomas were true negative. Under‐diagnosed smears were not related to cancer stage or last cytology report before diagnosis.     

Comparison of conventional Papanicolaou smear and SurePath® liquid-based cytology in the Copenhagen population screening programme for cervical cancer

OBJECTIVE: To compare diagnostic performance of conventional Papanicolaou smear with SurePath liquid-based cytology in a population screening programme. METHODS: A retrospective comparison was performed on data from two 18-month periods of the screening programme for cervical cancer in the municipality of Copenhagen with conventional Papanicolaou technique (n = 82,116) and liquid-based cytology (n = 84,414). RESULTS: After the conversion to liquid-based cytology the percentage of unsatisfactory samples decreased from 2.3% to 0.3% (P < 0.001), whereas the number of normal cervical samples lacking an endocervical component increased from 8.5% to 8.9% (P < 0.005). The percentage of samples with atypical cells and cells suspicious for malignancy increased from 3% to 4.2% (P < 0.001) and from 1.9% to 2.4% (P < 0.001), respectively. The subsequent histological follow-up showed normal findings decreased from 70.5% to 68.9% and from 28.0% to 26.1%, respectively. However, in relation to the entire screening populations, there was an increase of normal findings from 2.12% to 2.89% after primary atypical diagnosis and from 0.53% to 0.62% after diagnosis of suspicious cells after conversion to the liquid-based technique. CONCLUSIONS: This study showed the number of unsatisfactory samples to be significantly reduced with the liquid-based technique. The data suggest that there is an increased detection rate of cervical precancerous lesions with liquid-based cytology, but the number of false positive tests is still high. The specificity of the two tests seems similar, but this cannot be ascertained exactly, because of the fact that follow-up of negative cases is unavailable.     

Diagnostic and therapeutic dilemma associated with atypical glandular cells on liquid‐based cervical cytology

K. Chummun, M. Fitzpatrick, P. Lenehan, P. Boylan, E. Mooney and G. Flannelly
Diagnostic and therapeutic dilemma associated with atypical glandular cells on liquid‐based cervical cytology Background: In 2008, the management of women in Ireland with atypical glandular cells changed to immediate referral to colposcopy. The optimal management of these women is unclear. A balance between the detection of occult disease and overtreatment is required. Methods: Our study aim was to document the experience of this policy at the National Maternity Hospital, Dublin. Information from the computerized data management system was analysed with the statistical package SPSS. Results: In 2009, 156 women attended colposcopy following a single atypical glandular cell diagnosis on liquid‐based cytology. The mean age was 41 years. Thirty (19.2%) women had abnormal vaginal bleeding, 31 (19.9%) were smokers and 34 (21.8%) had received previous treatment. The colposcopy was satisfactory in 125 (80.1%) and unsatisfactory in 31 (19.9%). Cervical histology was available for 146 (93.6%) women: 57 excisional procedures and 89 diagnostic biopsies. Abnormal histology was detected in 46 women (31.5%). Four women (2.7%) had invasive cancer, five (3.4%) had adenocarcinoma in situ, 21 (14.4%) had cervical intraepithelial neoplasia (CIN) grade 2 or 3 and 16 (11.0%) had CIN1. No abnormality was detected in 100 women (68.5%), including 35 (61.4%) of those who had undergone excisional procedures. The colposcopic impression in this group was unsatisfactory in 10 women (28.6%), glandular abnormalities in six (17.1%), high‐ and low‐grade changes in 12 (34.2%) and six (17.1%) women, respectively, and normal in one (2.9%). The findings were essentially negative in the remaining 10 women: overall, 30 (19.2%) of the 156 women referred to colposcopy had at least CIN2. Conclusion: This study confirmed significant levels of high‐grade disease in women referred to colposcopy with atypical glandular cells on cytology. Concerns about undetected endocervical disease resulted in high levels of negative excisional biopsies. Alternative strategies, including endometrial sampling, human papillomavirus testing and discussion at clinicopathological meeting, should be considered.     

The ideal strategy for cervical cancer screening in Japan: Result from the Fukui Cervical Cancer Screening Study

Introduction

The aims of the Fukui Cervical Cancer Screening (FCCS) study are to determine the frequency of women with high‐risk HPV (hrHPV), whether HPV16 or HPV18 (HPV16/18), in the Japanese cancer screening population for the first time and to identify the best strategy for cervical cancer screening in Japan.

Methods

This study enrolled 7584 women aged ≥25 years who were undergoing routine screening. All women underwent LBC and cobas HPV tests. Women with abnormal cytology, whether hrHPV positive or negative; women with hrHPV positivity with either normal or abnormal cytology; and women randomly selected from women with normal cytology and negative hrHPV negative were referred for colposcopy.

Results

The prevalences of hrHPV positivity and HPV16/18 positivity were 6.8% and 1.7%, respectively. The baseline data from the FCCS study showed that the combination of HPV tests and cytology was more sensitive than cytology with respect to the detection of intraepithelial neoplasia grade 2 or worse. However, the specificity (94.1%) of the co‐testing strategy that required all women with abnormal cytology or hrHPV positivity to be referred for colposcopy was much lower than that (97.8%) of cytology. The sensitivity and specificity of the co‐testing strategy that required only women with abnormal cytology or HPV16/18 positivity to undergo colposcopy were 85.5% and 97.0%, respectively.

Conclusion

The baseline data from the FCCS study suggest that a cervical cancer screening strategy in which only women with abnormal cytology or HPV16/18 positivity undergo colposcopy offers a more balanced sensitivity and specificity than other strategies.     

Which women default from follow‐up cervical cytology tests? A cohort study within the TOMBOLA trial

L. Sharp, S. Cotton, A. Thornton, N. Gray, D. Whynes, L. Smart, N. Waugh, I. Duncan, M. Cruickshank and J. Little, on behalf of the TOMBOLA Group Which women default from follow‐up cervical cytology tests? A cohort study within the TOMBOLA trial Objective: To identify factors associated with default from follow‐up cervical cytology tests. Methods: A cohort study was conducted involving 2166 women, aged 20–59, with recent low‐grade cervical cytology taken within the NHS Cervical Screening Programmes in Scotland and England, and managed by 6‐monthly cytology in primary care. For the first (6‐month) and second (12‐month) surveillance cytology tests separately, women were categorized as ‘on‐time attendees’ (attended ≤6 months of test being due), ‘late attendees’ (attended greater than 6 months after test was due) or ‘non‐attendees’ (failed to attend). Multivariate odds ratios (ORs) were computed for factors associated with late and non‐attendance. Results: For the first surveillance test, risk of non‐attendance was significantly higher in younger women, those without post‐secondary education, and non‐users of prescribed contraception. Factors significantly associated with late attendance for the first test were the same as for non‐attendance, plus current smoking and having children. The most important predictor of non‐attendance for the second surveillance test was late attendance for the first test (OR = 9.65; 95% CI, 6.60–16.62). Non‐attendance for the second test was also significantly higher among women who were younger, smokers and had negative cytology on the first surveillance test. Late attendance for the second surveillance test was higher in women who were younger, smokers, had children and attended late for the first test. Conclusions: Women at highest risk of default from follow‐up cytology tend to be young, smoke, lack post‐secondary education, and have defaulted from a previous surveillance appointment. Tackling default will require development of targeted strategies to encourage attendance and research to better understand the reasons underpinning default.     

Vaginal vault smears –''know more – do less'': a questionnaire survey of primary health care practitioners

BACKGROUND: The vaginal vault smear is a test for cellular atypia in women who have undergone a hysterectomy. In asymptomatic women the test has poor sensitivity and specificity. Current guidelines recommend: vault smears should not be used after hysterectomy for benign pathology; two vault smears (6 and 12 months postsurgery) should be taken when there is evidence of completely excised CIN II/III in the specimen. AIM: To describe primary health care professionals' self-reported knowledge and behaviour relating to the use of vault smears. DESIGN OF STUDY: Questionnaire. SETTING: South Birmingham. METHODS: Postal questionnaire survey to primary health care professionals (general practitioners and practice nurses, n = 424). Results: Response rate 80.0%, completed response rate 68.9%. Mean knowledge score was 7.3 out of possible 12 (SD 1.9); range 0-10. No significant differences were observed between GPs and practice nurses in knowledge scores, although differences were noted in the frequency of performing vault smears. An inverse relationship was observed between frequency of performing vault smears and level of knowledge about the test. There was a positive association between requesting further information and the 'knowledge score'. Only 11% correctly answered a question based on current guidelines. CONCLUSIONS: Knowledge of current guidelines was poor. Those who undertook fewest vault smears appeared best informed. This suggests that if all primary care professionals practised according to current guidelines, the number of vault smears performed may be reduced. Unnecessary vault smears may cause additional anxiety in women and have financial consequences for the NHS.     

Primary HPV testing: a proposal for co‐testing in initial rounds of screening to optimise sensitivity of cervical cancer screening

As explained by Kitchener in a previous issue of Cytopathology (2015; 26 :4‐6), primary human papillomavirus (HPV) testing is likely to be introduced in the UK for all women aged 25–64 years following pilot site studies already in place. This will be necessary when the prevalence of cervical cancer and its precursors declines when vaccination takes effect but there is a risk in abandoning cytology as a primary test: a risk that would be most apparent in the present unvaccinated population in which the prevalence of cervical cancer and its precursors is exceptionally high. HPV testing is more sensitive than cytology but has a significant false‐negative rate that could be detrimental to a successful screening programme if introduced without cytology backup. Accurate cytology would be needed for triage and could be compromised if HPV‐negative tests were excluded from examination. This article proposes a compromise: cytology and HPV co‐testing for the first two screening tests to optimise the sensitivity of the test as a whole. Registrations of invasive and in situ carcinoma of the uterine cervix in England indicate that the prevalence of the disease is highest in young women in the early rounds of screening. Calculations of the likely impact on the workload of this proposal have been based on a service evaluation of 295 cytology tests received at St Thomas’ Hospital, which suggests that the volume of cytology tests would be reduced by approximately 60% compared with 80% for primary HPV testing alone. This proposal should be debated openly before irrevocable changes are made to a skilled workforce.     

Use of the ThinPrep Imaging System for internal quality control of cervical cytology

T. Heard, A. Chandra, G. Culora, S.S. Gupta, A. Herbert and M. Morgan
Use of the ThinPrep Imaging System for internal quality control of cervical cytology Objective: To audit the use of the ThinPrep Imaging System (TIS) for internal quality control (IQC) in the place of rapid review (RR), and to compare its performance with routine primary screening. Method: During 9 months, 16 462 ThinPrep slides were processed by TIS. Slides were initially reviewed using the TIS review scope, as recommended by the manufacturer: 22 fields of view were observed and, if considered abnormal, a full microscopic review was conducted using the review scope. Different biomedical scientists (BMSs), working on each procedure in rotation, performed batches of TIS‐assisted quality control and routine primary screening independently on unmarked slides. Any slides with abnormalities detected by either method were referred to a consultant pathologist or advanced BMS practitioner for a final report. TIS results were compared with both previous records of RR and routine primary screening carried out on the same slides. We used the UK terminology in which ‘dyskaryosis’ is equivalent to squamous intraepithelial lesion (SIL) and borderline to atypical (including squamous and glandular cells). Results: TIS preview detected significantly more high‐grade dyskaryosis compared with RR during the previous 4 years: 2.0–4.2 compared with 0.1–1.8 detected per 1000 slides (P = 0.0001). TIS and routine screening were equivalent in sensitivity and specificity for the final cytology result, but BMSs were significantly more likely to classify slides as dyskaryotic rather than borderline when using TIS compared with routine screening. Referrals for potentially high‐grade abnormalities detected by TIS‐assisted IQC alone found 28 biopsies of at least cervical intraepithelial neoplasia grade 2 (CIN2+), whereas 15 CIN2+ biopsies were found on routine screening but missed using TIS. There was no significant change in the rates of inadequate tests, high‐ or low‐grade cytological abnormalities, or positive predictive value for CIN2+ when TIS was in use. Conclusions: Screening with TIS was more sensitive than RR for IQC, providing a rescreening method equivalent to routine primary screening in overall accuracy.     

The number of dyskaryotic cells on an initial ThinPrep® cervical sample showing mild dyskaryosis has predictive value

OBJECTIVES: Recent National Health Service Cervical Screening Programme (NHSCSP) guidelines suggest referral for colposcopy following an initial result of mild dyskaryosis. The aim of this study was to investigate if the number of dyskaryotic cells counted on an initial ThinPrep cervical sample showing mild dyskaryosis has predictive value. METHODS: Cases of mild dyskaryosis on ThinPrep cervical samples from 2002 were retrieved from the cytology department records of St Luke's Hospital. A total of 123 sequential cases with a first-time result of mild dyskaryosis on ThinPrep slides with follow-up cytology available in the same institution were identified. While blinded to outcome, the number of dyskaryotic cells was counted in each case. Follow-up colposcopy/histology information was retrieved where indicated. The number of dyskaryotic cells counted on each slide was collated with outcome data. RESULTS: Of the 123 cases, six women were lost to follow-up. Seventy-three had a negative outcome, 27 had a low-grade outcome and 17 had a high-grade outcome. Only one of 17 high-grade outcome cases had < or = 15 dyskaryotic cells on the initial slide. The distribution of women with a negative/low-grade outcome and those with a high-grade outcome with >15 and < or = 15 dyskaryotic cells on the initial slide was tested using a chi-square test (P = 0.008). The negative predictive value for a high-grade outcome when < or = 15 dyskaryotic cells were present on the initial slide was 97.7%. CONCLUSION: The number of dyskaryotic cells on ThinPrep slides showing mild cervical dyskaryosis has predictive value. The number of dyskaryotic cells may be used to select women suitable for cytological rather than colposcopic follow-up.     

Micronucleus scoring in liver fine needle aspiration cytology

C.‐H. Wen, C.‐H. Lin, S.‐C. Tsao, Y.‐C. Su, M.‐H. Tsai and C.‐Y. Chai
Micronucleus scoring in liver fine needle aspiration cytology Objective: This study evaluated the role of the micronucleus (MN) in liver fine needle aspiration (FNA) cytology. Methods: Histological features of 75 cases of hepatocellular carcinoma (HCC), of which 25 were well differentiated, 37 moderately differentiated and 13 poorly differentiated, and 58 benign hepatic lesions (total, 133 cases) were correlated with MN expression observed in FNA smears reported as benign (n = 40), atypical (n = 14), suspicious (n = 30) and malignant (n = 49). Results: Stepwise increases in the MN score (0.4 ± 0.6, 1.2 ± 1.3, 6.3 ± 4.2 and 14.3 ± 8.8) correlated with the degree of cytological abnormality: benign, atypia, suspicious and malignant, respectively. The mean MN scores for well‐, moderately and poorly differentiated HCC were 5.4 ± 2.2, 11.5 ± 4.5 and 24.9 ± 9.1, respectively, which was significantly different between malignant and suspicious (P < 0.0001), between suspicious and atypical (P = 0.008) but not between atypical and benign. The MN scores differed significantly between all degrees of differentiation of HCC and between the HCC and benign hepatic lesions (P < 0.0001). High sensitivity, specificity and accuracy of liver FNA for diagnosing HCC (96%, 98%, and 96%, respectively) were obtained at a cutoff of three for the MN score. Conclusions: The MN score is an effective HCC biomarker and has a good potential use as an ancillary tool for diagnosing HCC using FNA cytology.     

Risk of significant gynaecological pathology in women with ?glandular neoplasia on cervical cytology

A. Talaat, D. Brinkmann, J. Dhundee, Y. Hana, J. Bevan, R. Irvine, S. Bailey and R. Woolas
Risk of significant gynaecological pathology in women with ?glandular neoplasia on cervical cytology Objective: To review the risk of pre‐invasive and invasive gynaecological pathology in women referred with cervical cytology reporting ?glandular neoplasia. Methods: Review of the case notes of all women referred with cervical cytology reported as ?glandular neoplasia between January 1999 and December 2008 at two UK hospitals: Portsmouth Hospitals NHS Trust and Queen Mary’s Hospital Sidcup. The category of ‘borderline nuclear change in endocervical cells’, result code 8 according to the national health service cancer screening programme (NHSCSP), was excluded from the study. Results: A total of 200 women were identified using the hospitals’ pathology computer systems. Invasive carcinoma was found in 48 women (24%): 28 endocervical adenocarcinomas, eight squamous cell carcinomas (SCC), ten endometrial and two ovarian adenocarcinomas. Pre‐invasive neoplasia was found in 115 (57.5%), including 14 cervical glandular intraepithelial neoplasia (CGIN), 31 cervical intraepithelial neoplasia (CIN) grade 2/3 and 70 concomitant CGIN and CIN2/3. CIN1/HPV was found in 25, simple endometrial hyperplasia in three and no histological abnormality in three. Thirty‐four (70.8%) of 48 invasive carcinomas (of which 23 were endocervical adenocarcinomas) were in asymptomatic women investigated for abnormal cytology. Fourteen of 34 (41.4%) of those with ?glandular neoplasia thought to be endometrial were CGIN or CIN2/3. Colposcopic appearances were normal in 47.6% of women with pure cervical glandular neoplasia (adenocarcinoma or CGIN) compared with 12.8% with squamous cell lesions (CIN2/3 or SCC): P = 0.0001. Thus, colposcopy was more sensitive for detecting squamous cell abnormalities than their glandular counterparts. Although cervical adenocarcinomas are less amenable to prevention by screening than cervical SCC, in our study cervical cytology predominantly detected these abnormalities at their early asymptomatic stages. Conclusion: At least CIN2 was found in 81.5% in women referred with cervical cytology reporting ?glandular neoplasia. A thorough evaluation of the whole genital tract is needed if colposcopy is negative.     

Is a liquid‐based cytology more sensitive than a conventional Pap smear?

K. Sigurdsson
Is a liquid‐based cytology more sensitive than a conventional Pap smear? Background: The comparative sensitivity of liquid‐based cytology (LBC) test and conventional Papanicolaou (Pap) smears is controversial. Material and methods: This study analyses the distribution of cytology, histology, colposcopy and large loop excision of the transformation zone among women screened in Iceland with LBC at the Cancer Detection Clinic in Reykjavik and with a conventional Pap smear outside the Detection Clinic in 2007–2011. The study material included 42 654 LBC tests from 20 439 women and 103 909 Pap smears from 61 574 women. The period 2000–2004 is used to correct for potential bias as a result of unequal distribution of the studied parameters between the study sites before the introduction of LBC. Results: The observed results indicated that women screened with an LBC sample had significantly decreased detection rates of inadequate smears, increased detection of low‐grade squamous intraepithelial lesion (LSIL)/atypical cytology and referrals to colposcopy, and an increased detection rate of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) irrespective of age. LBC increased significantly the detection rates of high‐grade squamous intraepithelial lesion or worse (HSIL+) cytology and CIN3+ histology only in women under 40 years of age. Taking into consideration the unequal prevalence of the studied parameters between the study sites in 2000–2004 indicated, however, that LBC only affected the rate of inadequate and low‐grade cytology tests under the age of 40 years. Positive predictive values for CIN2+ were not significantly different between the tests. Conclusions: The study results support the view that LBC is no more sensitive than Pap smears for the detection of HSIL+ and CIN2+ irrespective of age. LBC decreased the rate of inadequate smears, but increased the rate of low‐grade cytology under the age of 40 years and decreased the total rate of abnormal smears over the age of 40 years.