Audit of laboratory sensitivity of human papillomavirus and cytology testing in a cervical screening program.

The globally recommended public health policy for cervical screening is primary human papillomavirus (HPV) screening with cytology triaging of positives. To ensure optimal quality of laboratory services we have conducted regular audits of cervical smears taken before cervical cancer or cancer in situ (CIN3+) within an HPV-based screening program. The central cervical screening laboratory of Stockholm, Sweden, identified cases of CIN3+ who had had a previous cervical screening test up to 3 years before and randomly selected 300 cervical liquid-based cytology (LBC) samples for auditing. HPV testing with Roche Cobas was performed either at screening or with biobanked samples. HPV negative samples and subsequent biopsies were retrieved and tested with modified general primer HPV PCR and, if still HPV-negative, the LBCs and biopsies were whole genome sequenced. The Cobas 4800 detected HPV in 1020/1052 (97.0%) LBC samples taken before CIN3+. Further analyses found HPV in 28 samples, with nine of those containing HPV types not targeted by the Cobas 4800 test. There were 4 specimens (4/1052, 0.4%) where no HPV was detected. By comparison, the proportion of CIN3+ cases that were positive in a previous cytology were 91.6%. We find that the routine HPV screening test had a sensitivity in the real-life screening program of 97.0%. Regular laboratory audits of cervical samples taken before CIN3+ can be readily performed within a real-life screening program and provide assurance that the laboratory of the real-life program has the expected performance.

Trends in the use of cervical cancer screening tests in a large medical claims database, United States, 2013-2019.

OBJECTIVE: To examine trends in the use of cervical cancer screening tests during 2013-2019 among commercially insured women. METHODS: The study population included women of all ages with continuous enrollment each year in the IBM MarketScan commercial or Medicare supplemental databases and without known history of cervical cancer or precancer (range = 6.9-9.8 million women per year). Annual cervical cancer screening test use was examined by three modalities: cytology alone, cytology plus HPV testing (cotesting), and HPV testing alone. Trends were assessed using 2-sided Poisson regression. RESULTS: Use of cytology alone decreased from 34.2% in 2013 to 26.4% in 2019 among women aged 21-29 years (P < .0001). Among women aged 30-64 years, use of cytology alone decreased from 18.9% in 2013 to 8.6% in 2019 (P < .0001), whereas cotesting use increased from 14.9% in 2013 to 19.3% in 2019 (P < .0001). Annual test use for HPV testing alone was below 0.5% in all age groups throughout the study period. Annually, 8.7%-13.6% of women aged 18-20 years received cervical cancer screening. There were persistent differences in screening test use by metropolitan residence and census regions despite similar temporal trends. CONCLUSIONS: Temporal changes in the use of cervical cancer screening tests among commercially insured women track changes in clinical guidelines. Screening test use among individuals younger than 21 years shows that many young women are inappropriately screened for cervical cancer.

Lesion-targeted cytology to improve cytological sampling for atypical polypoid adenomyomas of the uterus: A case series and review of the literature.

OBJECTIVE: Atypical polypoid adenomyomas (APAs) are uncommon tumours consisting of atypical endometrioid glands and fibromyomatous stroma. Identifying the biphasic nature of atypical glandular components and spindle mesenchymal components without atypia is crucial for the cytological diagnosis of APA. We investigated the utility of lesion-targeted cytology (LTC) to directly collect firm spindle components. METHODS: We recruited seven consecutive surgical patients who underwent cytological examinations before surgery and were diagnosed with APA on postoperative histological examinations. Cytological smears were obtained by routine sampling in five cases and by targeted sampling using transvaginal ultrasonography, that is, LTC, in two cases. We retrospectively analysed the cytological findings from our cases and compared them to those of APA cases previously reported in the English literature. RESULTS: Among 5/7 cases that involved routine cytological sampling, normal cytological findings were found in 2 and atypical glandular cells were found in 3, but spindle cells from mesenchymal components were not detected. In contrast, among 2/7 cases in which sampling involved LTC, spindle cells without atypia, in addition to atypical glandular cells were found. CONCLUSIONS: Lesion-targeted cytology is useful to assess mesenchymal components of APAs and may improve the cytological diagnosis of APA.

Clinical Controversies in Cervical Cancer Screening.

Through the implementation of systematic cervical cancer screening in the mid-20th century, the United States and other developed countries have seen death rates from cervical cancer decreased by ≥70%.The purpose of this article is to address several of the most controversial issues associated with cervical cancer screening recommendations in light of historical and evolving data. In this article, we will explore the controversies around the age at which to initiate and exit screening, human papilloma virus testing alone as a primary screening approach, and the impact of human papilloma virus vaccination on cervical cancer rates.

Ensuring quality in cervical screening programmes based on molecular human papillomavirus testing.

The increased use of human papillomavirus testing within cervical screening programmes necessarily brings about changes to the laboratory services required to support them. A crucial element of such services is to demonstrate initial and ongoing quality of the test (and associated processes). In this review, we outline some of the quality considerations and challenges with an emphasis on the laboratory including assay and platform validation, internal quality control selection and strengths and weaknesses of external quality assurance schemes. The influence and role of key external entities, including regulatory agencies, guideline groups, programme commissioners and commercial providers, are also discussed.

Good concordance of HPV detection between cervico-vaginal self-samples and general practitioner-collected samples using the Cobas 4800 HPV DNA test.

BACKGROUND: Studies comparing self-samples and clinician-collected samples for high-risk human papillomavirus (HPV) detection using clinically validated PCR-based HPV DNA assays are limited. We measured the concordance of HPV detection between home-based self-sampling and general practitioner (GP) sampling using the Cobas 4800 HPV DNA test and studied women's accept of home-based self-sampling. METHODS: Paired GP-collected samples and cervico-vaginal self-samples were obtained from 213 women aged 30-59 years diagnosed with ASC-US within the cervical cancer screening program. After undergoing cervical cytology at their GP, the women collected a self-sample with the Evalyn Brush at home and completed a questionnaire. Both samples were HPV-tested using the Cobas 4800 test. Histology results were available for those who tested HPV positive in GP-collected samples. RESULTS: We observed good concordance for HPV detection between self-samples and GP-collected samples (κ: 0.70, 95% CI: 0.58-0.81). No underlying CIN2+ cases were missed by self-sampling. Women evaluated that self-sampling was easy (97.2%, 95% CI: 93.9-98.9%) and comfortable (94.8%, 95% CI: 90.9-97.4%). CONCLUSIONS: Home-based self-sampling using the Evalyn Brush and the Cobas 4800 test is an applicable and reliable alternative to GP-sampling.

Screening for Cervical Cancer: US Preventive Services Task Force Recommendation Statement.

Importance: The number of deaths from cervical cancer in the United States has decreased substantially since the implementation of widespread cervical cancer screening and has declined from 2.8 to 2.3 deaths per 100 000 women from 2000 to 2015. Objective: To update the US Preventive Services Task Force (USPSTF) 2012 recommendation on screening for cervical cancer. Evidence Review: The USPSTF reviewed the evidence on screening for cervical cancer, with a focus on clinical trials and cohort studies that evaluated screening with high-risk human papillomavirus (hrHPV) testing alone or hrHPV and cytology together (cotesting) compared with cervical cytology alone. The USPSTF also commissioned a decision analysis model to evaluate the age at which to begin and end screening, the optimal interval for screening, the effectiveness of different screening strategies, and related benefits and harms of different screening strategies. Findings: Screening with cervical cytology alone, primary hrHPV testing alone, or cotesting can detect high-grade precancerous cervical lesions and cervical cancer. Screening women aged 21 to 65 years substantially reduces cervical cancer incidence and mortality. The harms of screening for cervical cancer in women aged 30 to 65 years are moderate. The USPSTF concludes with high certainty that the benefits of screening every 3 years with cytology alone in women aged 21 to 29 years substantially outweigh the harms. The USPSTF concludes with high certainty that the benefits of screening every 3 years with cytology alone, every 5 years with hrHPV testing alone, or every 5 years with both tests (cotesting) in women aged 30 to 65 years outweigh the harms. Screening women older than 65 years who have had adequate prior screening and women younger than 21 years does not provide significant benefit. Screening women who have had a hysterectomy with removal of the cervix for indications other than a high-grade precancerous lesion or cervical cancer provides no benefit. The USPSTF concludes with moderate to high certainty that screening women older than 65 years who have had adequate prior screening and are not otherwise at high risk for cervical cancer, screening women younger than 21 years, and screening women who have had a hysterectomy with removal of the cervix for indications other than a high-grade precancerous lesion or cervical cancer does not result in a positive net benefit. Conclusions and Recommendation: The USPSTF recommends screening for cervical cancer every 3 years with cervical cytology alone in women aged 21 to 29 years. (A recommendation) The USPSTF recommends screening every 3 years with cervical cytology alone, every 5 years with hrHPV testing alone, or every 5 years with hrHPV testing in combination with cytology (cotesting) in women aged 30 to 65 years. (A recommendation) The USPSTF recommends against screening for cervical cancer in women younger than 21 years. (D recommendation) The USPSTF recommends against screening for cervical cancer in women older than 65 years who have had adequate prior screening and are not otherwise at high risk for cervical cancer. (D recommendation) The USPSTF recommends against screening for cervical cancer in women who have had a hysterectomy with removal of the cervix and do not have a history of a high-grade precancerous lesion or cervical cancer. (D recommendation).

Barriers to HPV self-sampling and cytology among low-income indigenous women in rural areas of a middle-income setting: a qualitative study.

BACKGROUND: Data is needed about barriers to self-collection of Human Papillomavirus (HPV) samples and cytology among low-income, disadvantaged women living in rural areas of lower-income countries as these women are at increased risk of cervical cancer mortality. METHODS: Individual interviews (n = 29), focus groups (n = 7, 5-11 participants) and discussion groups (n = 2, 18-25 participants) were organized with women from three indigenous ethnic groups residing in rural areas in Mexico, after they were provided with free, self-sampled HPV tests. These groups are low-income, underserved by healthcare and have historically been on the receiving end of racism and social exclusion. Descriptive, qualitative content analysis was done, including two cycles of coding. RESULTS: Interview and focus/discussion group data indicate women had limited understanding of HPV's role in cervical cancer etiology. They identified HPV's existence, that cytology detects cervical cancer, the need for regular testing and that cervical cancer is sexually transmitted. Organizational barriers to clinic-based cytology included irregular supplies of disposable speculums, distance to clinics and lack of clear communication by healthcare personnel. Women considered self-collected HPV-testing easy, less embarrassing and less painful than cytology, an opportunity for self-care and most felt they understood how to take a self-sample after a 20-min explanation. Some women feared hurting themselves when taking the self-sample or that they would take the sample incorrectly, which they worried would make the test useless. Attending HPV-testing in groups facilitated use by allowing women to discuss their doubts and fears before doing self-collection of the sample or to ask other women who were the first to do the self-sampling what the experience had been like (whether it hurt and how easy it was). Lack of indoor bathrooms was a barrier to doing HPV self-sampling at home, when those homes were resource-poor (one-room dwellings). CONCLUSIONS: Low-income, indigenous Mexican women residing in rural, underserved areas identified their need for cervical cancer screening but encountered multiple barriers to cytology-based screening. They found a number of advantages of HPV self-sampled tests. Employing self-collected HPV-testing instead of cytology could resolve some but not all gender-related, organizational or technical quality-of-care issues within cervical cancer detection and control programs.

Technical proficiency in cytopathology: assessment through external quality assurance.

OBJECTIVE: To assess both the feasibility and value of conducting an external quality assurance programme concerning technical aspects of cytopathology laboratory practice, and the interest by laboratories in enrolling in such a programme. METHODS: Six technical surveys, comprising staining exercises and questionnaires relating to laboratory practice, were distributed over a 4-year period to the approximately 220 laboratories enrolled in the RCPAQAP Cytopathology slide survey modules. Staining exercises using the Papanicolaou and Romanowsky techniques, the preparation of urine and body fluid specimens and immunocytochemistry on the cell block material were assessed. Accompanying relevant questionnaires were included, and one survey comprised a questionnaire alone concerning the collection of urinary tract and body fluid samples. RESULTS: Provision of an external cytopathology technical module was feasible for the RCPAQAP and participation rates (maximum of 87% per survey; average 68% for stained slides and 66% for questionnaires) were commendable, particularly considering these were optional undertakings with some exercises not applicable to all laboratories. The great majority of submitted slides were scored as satisfactory, and there was an especially high standard for the immunocytochemical staining exercise with 95% considered satisfactory, including 50.6% with a perfect score. Reasons for suboptimal scores were provided for potential quality improvement for interested laboratories. A wealth of information relating to laboratory practice was provided to the RCPAQAP which was collated and summarised for laboratory use. CONCLUSIONS: The provision of a technical module in cytopathology is both a feasible and valuable undertaking of interest to laboratories which should become standard practice for cytopathology external quality assurance providers.

Accuracy of self-collected human papillomavirus samples from Japanese women with abnormal cervical cytology.

AIM: The aim of this study was to assess the accuracy of self-collected vaginal samples compared with physician-collected cervical samples for high-risk human papillomavirus (HPV) testing in Japanese women with abnormal cervical cytology. We also assessed the acceptability of self-collected HPV (sHPV) testing using a questionnaire. METHODS: Women aged 20-69 years (n = 136) attending Yokohama City University Hospital because of abnormal cervical cytology between April 2014 and January 2015 were enrolled in this study. Cervical samples for conventional cytology and physician-collected HPV (pHPV) testing were obtained before colposcopic examination. After this examination, patients were asked to provide a self-sampled vaginal specimen (sHPV) at home, some time between the following day and the next week and to complete a self-sampling acceptability questionnaire. RESULTS: The overall positive rates of HPV detection with pHPV and sHPV testing were 61.0% (83/136) and 40.4% (55/136), respectively (P < 0.001). sHPV testing had a lower sensitivity compared to pHPV for detection of cervical intraepithelial neoplasia (CIN)2 or worse (CIN2+: 59.4% vs 100%, P < 0.001; CIN3: 66.7% vs 100%, P = 0.248). There were no statistically significant differences in the sensitivity to detect CIN3 among pHPV testing, sHPV testing, and cytology. The self-collecting device had good acceptability. CONCLUSION: sHPV testing is a possible technique with which to improve poor cervical cancer screening uptake rates in Japan; however, the sensitivity to detect CIN2+ lesions must improve before it can be a substitute for conventional cytology or pHPV testing. Further large-scale acceptability studies involving non-responders are also needed before practical application.

Comparing Papanicolaou test results obtained during pregnancy and post-partum.

AIM: Cervical cancer onset initially occurs during youth. Papanicolaou tests performed in early pregnancy can detect cervical cancer; however, Papanicolaou tests during pregnancy have been noted to be inaccurate, reflecting changes associated with pregnancy. Therefore, we assessed the effect of pregnancy on Papanicolaou test results. METHODS: Of 1351 pregnant women who delivered at Ise Red Cross Hospital between January 2010 and December 2014, 1213 underwent Papanicolaou tests at early pregnancy and post-partum. We compared the Papanicolaou test results. RESULTS: The results of the Papanicolaou test were different in 32 patients. Of the 1191 patients negative for intraepithelial lesions or malignancy in early pregnancy, 16 had other cytological abnormalities post-partum. We performed therapeutic conization post-partum in four patients. The Papanicolaou test results in early pregnancy of the four patients were negative for intraepithelial lesions or malignancy in one patient, atypical squamous cells of undetermined significance in one and high-grade squamous intraepithelial lesion in two. CONCLUSION: The results of the Papanicolaou test during pregnancy may not be accurate because of the influence of hormones associated with pregnancy. Taking advantage of the one-month post-partum screening visit can lead to early detection and treatment of cervical cancer in young people.

Evaluation of an enzymatic Chlamydia trachomatis point-of-care rapid assay in Rwanda: the BioChekSwab Rapid Test.

OBJECTIVES: We evaluated the performance of an enzymatic point-of-care rapid test for Chlamydia trachomatis (CT) (the BioChekSwab CT Rapid Test, EnZtek Diagnostics, Rio Vista, California, USA), which detects CT's Peptidase 123CBV enzyme and provides a result 15 min after specimen collection. METHODS: Two endocervical swabs, including one BioChekSwab, per person were obtained from 137 women who participated in a reproductive health study in Rwanda. The BioChekSwab was processed according to the manufacturer's instructions. A substrate was squirted over the swab by the study physician immediately after collection, and another reagent was released over the swab tip at arrival in the laboratory. The test was considered positive if a blue colour developed within 2 min. The other regular flocked endocervical swab was processed at the Institute of Tropical Medicine (ITM), Belgium, using a testing algorithm: Abbott RealTime CT/Neisseria gonorrhoeae (NG) assay with the confirmation of positive results by an in-house real-time PCR assay. RESULTS: Of the 137 women, nine were CT positive by the testing algorithm. All nine positive results were missed by the BioChekSwab assay and four false-positive results were obtained. The sensitivity was therefore 0% (95% CI 0% to 33.6%) and the specificity was 96.9% (95% CI 92.2% to 99.1%). CONCLUSIONS: The BioChekSwab Rapid Test, although ISO13485 certified and Conformitée Européenne (CE) labelled, lacked any sensitivity in our setting.

Daily peer review of abnormal cervical smears in the assessment of individual practice as an additional method of internal quality control.

OBJECTIVE: An important internal quality control system used in the Cancer Prevention and Research Institute cytopathology laboratory in Florence is the peer review procedure, based on the review of all abnormal cytological smears which routinely emerge. Peer review is an important training opportunity for all cytologists, especially for those with less experience. This article shows the results of the peer review procedure. METHODS: Of the 63 754 Papanicolaou (Pap) smears screened in 2011, 1086 were considered to be abnormal [at least atypical squamous cells of undetermined significance (ASC-US+)] on primary screening (selected by a single cytologist) and were subjected to the peer review procedure. The overall performance of the laboratory's cytologists was evaluated using a multiple rater analysis and the comparison of each cytologist with the final diagnosis. Further, the agreement was assessed by means of Cohen's kappa and weighted kappa statistics. RESULTS: In general, a moderate/substantial level of agreement between the ten cytologists and the final diagnoses was evident. Kappa values for each reader compared with the final diagnosis ranged from 0.54 to 0.69. The overall kappa value was 0.62 [95% confidence interval (CI), 0.58-0.66] and overall weighted kappa value was 0.76 (95% CI, 0.74-0.79). The category-specific agreement showed the lowest values for atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H). CONCLUSION: In summary, peer review represents an important internal quality control in the evaluation and improvement of inter-observer agreement and of the functioning of the laboratory as a whole. Multi-head microscope sessions may improve particularly the reproducibility of borderline diagnoses and, above all, can be an important training contribution for cytologists.

Prevalence of Trichomonas vaginalis in Women Visiting 2 Obstetrics and Gynecology Clinics in Daegu, South Korea.

This study explored epidemiological trends in trichomoniasis in Daegu, South Korea. Wet mount microscopy, PCR, and multiplex PCR were used to test for Trichomonas vaginalis in vaginal swab samples obtained from 621 women visiting 2 clinics in Daegu. Of the 621 women tested, microscopy detected T. vaginalis in 4 (0.6%) patients, PCR detected T. vaginalis in 19 (3.0%) patients, and multiplex PCR detected T. vaginalis in 12 (1.9%) patients. Testing via PCR demonstrated high sensitivity and high negative predictive value for T. vaginalis. Among the 19 women who tested positive for T. vaginalis according to PCR, 94.7% (18/19) reported vaginal signs and symptoms. Notably, more than 50% of T. vaginalis infections occurred in females younger than 30 years old, and 58% were unmarried. Multiplex PCR, which simultaneously detects pathogens from various sexually transmitted infections, revealed that 91.7% (11/12) of patients were infected with 2 or more pathogens. Mycoplasma hominis was the most prevalent co-infection pathogen with T. vaginalis, followed by Ureaplasma urealyticum and Chlamydia trachomatis. Our results indicate that PCR and multiplex PCR are the most sensitive tools for T. vaginalis diagnosis, rather than microscopy which has been routinely used to detect T. vaginalis infections in South Korea. Therefore, clinicians should take note of the high prevalence of T. vaginalis infections among adolescent and young women in order to prevent persistent infection and transmission of this disease.

Evaluation of Direct Visual Inspection of the Cervix in Detecting Cytology Diagnosed Squamous Intraepithelial Lesion in Women of known HIV Status. A Randomized Trial (CANHIV Study).

A two-arm, open label, randomized study, evaluated the test characteristics of visual inspection of cervix with Acetic acid(VIA) and Lugol?s Iodine(VILI) in detecting cytology diagnosed squamous intraepithelial lesion(SIL) in 1160 women of known HIV status in southwestern Nigerian. Using SIL as reference standard and the HIV status masked, VIA and VILI had similar test characteristics except for the positive predictive value in which VIA value of 91.5% was significantly higher than 77.7% for VILI ( p=0.01). Among HIV positive women, VILI performed poorly across all the 4 test characteristics compared to VIA. Among severely immuno-compromised HIV positive participants VILI performance was consistently below 80% across all test characteristics (sensitivity-70.0%; specificity-66.9%; positive predictive value-46.7%; negative predictive value(NPV)-50.0%) compared to VIA (Senstivity-71.3%; specificity-88.2%; positive predictive value-83.3%; negative predictive value -88.2). Our study shows that VILI is insufficiently sensitive and specific in the presence of HIV infection especially in those with severe immunosuppression. Based on VIA?s acceptable sensitivity and NPV in all situations, it is recommended for cervical cancer screening in HIV positive women and in settings of high HIV burden.

Usefulness of vaginal cytology tests in women with previous hysterectomy for benign diseases: assessment of 53,891 tests.

OBJECTIVE: To assess the value of vaginal screening cytology after hysterectomy for benign disease. METHODS: This cross-sectional study used cytology audit data from 2,512,039 screening tests in the metropolitan region of Campinas from 2000 to 2012; the object was to compare the prevalence of abnormal tests in women who had undergone a hysterectomy for benign diseases (n=53,891) to that of women who had had no hysterectomy. Prevalence ratios (95% confidence intervals, 95% CI) were determined, and chi-square analysis, modified by the Cochrane-Armitage test for trend, was used to investigate the effects of age. RESULTS: The prevalence of atypical squamous cells (ASC), low-grade squamous intraepithelial lesion (LSIL), and high-grade squamous intraepithelial lesion or squamous-cell carcinoma (HSIL/SCC) was 0.13%, 0.04% and 0.03%, respectively, in women who had undergone hysterectomy, and 0.93%, 0.51% and 0.26% in women who had not undergone hysterectomy. The prevalence ratios for ASC, LSIL and HSIL/SCC were 0.14 (0.11-0.17), 0.08 (0.06-0.13) and 0.13 (0.08-0.20), respectively, in women with a hysterectomy versus those without. For HSIL/SCC, the prevalence ratios were 0.09 and 0.29, respectively, for women <50 or ≥50 years. The prevalence rates in women with a previous hysterectomy showed no significant variation with age. CONCLUSION: The prevalence rates of ASC, LSIL and HSIL/SCC were significantly lower in women with a previous hysterectomy for benign disease compared with those observed in women with an intact uterine cervix. This study reinforces the view that there is no evidence that cytological screening is beneficial for women who have had a hysterectomy for benign disease.

Vaginal Cytology of the Laboratory Rat and Mouse: Review and Criteria for the Staging of the Estrous Cycle Using Stained Vaginal Smears.

Microscopic evaluation of the types of cells present in vaginal smears has long been used to document the stages of the estrous cycle in laboratory rats and mice and as an index of the functional status of the hypothalamic-pituitary-ovarian axis. The estrous cycle is generally divided into the four stages of proestrus, estrus, metestrus, and diestrus. On cytological evaluation, these stages are defined by the absence, presence, or proportion of 4 basic cell types as well as by the cell density and arrangement of the cells on the slide. Multiple references regarding the cytology of the rat and mouse estrous cycle are available. Many contemporary references and studies, however, have relatively abbreviated definitions of the stages, are in reference to direct wet mount preparations, or lack comprehensive illustrations. This has led to ambiguity and, in some cases, a loss of appreciation for the encountered nuances of dividing a steadily moving cycle into 4 stages. The aim of this review is to provide a detailed description, discussion, and illustration of vaginal cytology of the rat and mouse estrous cycle as it appears on smears stained with metachromatic stains.

The Pap Test and Bethesda 2014. "The reports of my demise have been greatly exaggerated." (after a quotation from Mark Twain).

The history of 'The Bethesda System' for reporting cervical cytology goes back almost 3 decades. This terminology and the process that created it have had a profound impact on the practice of cervical cytology for laboratorians and clinicians alike. The Bethesda conferences and their ensuing output have also set the stage for standardization of terminology across multiple organ systems, including both cytology and histology, have initiated significant research in the biology and cost-effective management for human papillomavirus-associated anogenital lesions, and, finally, have fostered worldwide unification of clinical management for these lesions. Herein, we summarize the process and rationale by which updates were made to the terminology in 2014 and outline the contents of the new, third edition of the Bethesda atlas and corresponding website.

Does Cytological Laboratory Holds the Responsibility for the Low Sensitivity of the PAP Test in Detecting Endometrial Cancer?

Endometrial cancer is the most common gynecological cancer but there is no economically justified screening method. Although we can detect endometrial cells in the sample using PAP test, many studies show low sensitivity and positive predictive value of PAP test for the diagnosis of endometrial cancer. The goal of this research was to determine significance of PAP test for the diagnostics of endometrial carcinoma. Sensitivity and specificity were analyzed with statistical parameters. VCE (vaginal, cervical, endocervical) smears of patients with histologically proven endometrial carcinoma were re-examined in order to determine the proportion of false negative results for endometrial cancer cells in the VCE samples. Study group consisted of all consecutive patients with PAP test performed at the Department of Clinical Cytology of the University Hospital Center Osijek from 2002 until the end of 2014. There was one inclusion criteria: subsequent hysterectomy or curettage within the six month after the PAP test, regardless of histological finding. From a total of 263 patients with previous PAP test and histologically proven endometrial cancer, endometrial cancer was cytologicaly diagnosed in 24.7% (including suspicious and positive findings), while 66.2% patients had normal cytological findings. The diagnostic value of PAP test in detection of endometrial cancer was statistically revealed with 25% sensitivity and 99% specificity. To determine false negative rate VCE samples were reviewed for patients with histologically proven endometrial cancer and negative VCE findings. There were a total of five negative results. In one case revision did not changed the original negative diagnosis, but benign endometrial cells, a lot of blood and inadequate cytohormonal status were found. In three out of four reviewed samples there were missed cells of endometrial adenocarcinoma. Review of remaining VCE sample upgraded the diagnosis from negative to suspicious for endometrial cancer. Proportion of error in the detection of endometrial cancer using cytological findings was 3.4% (true false negatives). Negative rate of the cytological findings in the detection of endometrial cancer was 66.2%. PAP test is not a suitable method for detection of endometrial carcinoma due to low sensitivity (25%). The main cause of negative findings in PAP test was lack of diagnostic cells in the sample.