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Objective: To compare the performance of cytology, HPV16/18 genotyping and PAX1/SOX1 methylation for the triage of high‐risk HPV‐positive cervical samples. Design: Retrospective analyses of archival samples collected from a large‐scale prospective randomised controlled trial. Setting/Sample: HPV‐positive women recruited from the general cervical screening population. Methods: 403 HPV‐positive samples including 113 normal, 173 low‐grade cervical intraepithelial neoplasia (LG‐CIN), 114 HG‐CIN and three cervical cancers. All samples were assessed by liquid‐based cytology, HPV genotyping and PAX1/SOX1 methylation. Main Outcome Measures: AUC (area under the curve), sensitivity and specificity for cytology, HPV16/18 genotyping and PAX1/SOX1 methylation for high‐grade (HG) premalignant cervical lesions. Results: PAX1 was more sensitive than cytology and HPV16/18 genotyping in detecting a HG lesion (CIN2+). The sensitivity for PAX1, SOX1, cytology and HPV16/18 were 73.5% (95% CI: 65.5–81.5), 41.9% (95% CI: 32.9–50.8), 48.7% (95% CI: 39.7–57.8) and 36.8% (95% CI: 28.0–45.5), respectively, and their respective specificities were 70.3% (95% CI: 65.0–75.6), 83.6% (95% CI: 79.3–87.9), 77.6% (95% CI: 72.8–82.5) and 67.1% (95% CI: 61.7–72.6), respectively. Overall, PAX1 gave the best AUC at 0.72. Adding SOX1 to PAX1 did not improve the AUC (0.68). Three hundred and twenty‐two women who did not have a HG lesion at baseline were followed up for two rounds of screening. Fewer women developed a HG lesion with a normal baseline PAX1 compared to women with a normal baseline cytology or negative HPV16/18 (8.4% vs. 14.5% and 17.5%, respectively). Conclusion: PAX1 triage for referral to colposcopy in HPV‐positive women may be superior to cytology and HPV16/18 genotyping. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Methods Results Conclusions This study aimed to investigate the supporting role of artificial intelligence (AI) in digital cervical cytology training.A total of 104 trainees completed both manual reading and AI‐assisted reading tests following the AI‐assisted digital training regimen. The interpretation scores and the testing time in different groups were compared. Also, the consistency, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of diagnoses were further analysed through the confusion matrix and inconsistency evaluation.The mean interpretation scores were significantly higher in the AI‐assisted group compared with the manual reading group (81.97 ± 16.670 vs. 67.98 ± 21.469, p < 0.001), accompanied by a reduction in mean interpretation time (32.13 ± 11.740 min vs. 11.36 ± 4.782 min, p < 0.001). The proportion of trainees' results with complete consistence (Category O) were improved from 0.645 to 0.803 and the averaged pairwise κ scores were improved from 0.535 (moderate) to 0.731 (good) with AI assistance. The number of correct answers, accuracies, sensitivities, specificities, PPV, NPV and κ scores of most class‐specific diagnoses (NILM, Fungi, HSV, LSIL, HSIL, AIS, AC) also improved with AI assistance. Moreover, 97.8% (89/91) of trainees reported substantial improvement in cervical cytology interpretation ability, and all participants (100%, 91/91) expressed a strong willingness to integrate AI‐assisted diagnosis into their future practice.The utilisation of an AI‐assisted digital cervical cytology training platform positively impacted trainee performance and received high satisfaction and acceptance among clinicians, suggesting its potential as a valuable adjunct to medical education. [ABSTRACT FROM AUTHOR]

Introduction: Specific diagnosis of endometrial carcinomas on cervical cytology is difficult with few useful cytomorphological clues reported. This study reviews a cohort of cervical cytology to investigate the presence of keratinization in atypical glandular cells (AGC), an undescribed cytomorphological clue for identifying endometrial endometrioid carcinomas on cervical cytology. Methods: Cervical cytology slides from patients with a histologic diagnosis of endometrial endometrioid carcinoma were reviewed for the presence of keratinization associated with AGCs. Corresponding histology slides were reviewed for tumour grading and degree of squamous differentiation. Results: In total, 42 cases of cervical cytology specimens from 41 patients were retrieved, including 7 (16.7%) with keratinization associated with AGCs seen and 35 (83.3%) without. Comparison of histologic grading did not demonstrate an association with the presence of keratinization on cytology (p = 0.565). Corresponding histology slides were available for 37 cases. Cytologic and histologic keratinization were associated statistically (p = 0.002). Frank keratinization was seen on histologic slides of five cases, with four also showing cytologic keratinization. Area of squamous differentiation, including squamous morule formation, did not correlate with keratinization on cytologic preparation (p = 0.185). Conclusion: Histologic and cytologic keratinization are observed in endometrioid endometrial carcinomas. Such is reflected in cervical cytology by the presence of orangeophilic, rigid and acellular fragments within or associated with AGC clusters. Keratinization, when identified with AGCs, should be regarded as a cytologic clue suggestive of an endometroid carcinoma of endometrial origin. [ABSTRACT FROM AUTHOR]

Objective: The Papanicolaou (Pap) smear test is a standard screening test that detects cervical lesions and cancers. In this multicentric study, we performed a retrospective analysis of cytological results associated with atypical glandular cells, not otherwise specified (AGC‐NOS). Methods: We retrospectively reviewed Pap smear tests that resulted as AGC‐NOS. A total of 254 women who underwent colposcopy due to a Pap smear result of AGC‐NOS were included the study between 2003 and 2021. The ages, Pap smear results, HPV results if any, colposcopic biopsy results, endocervical and endometrial pathology results, and management of these patients were analysed. Results: Two hundred fifty‐four patients with AGC‐NOS Pap smear results were included in the study. A total of 70 (27.6%) patients had cervical and endometrial premalignant or malignant lesions. Malignancy was observed in 17 (6.7%) patients (endometrium, n = 11 [4.3%]; cervix, n = 6 [2.4%]). Isolated premalignant or malignant lesions of the cervix and endometrium were detected in 57 (22.4%) and 12 (4.7%) patients, respectively. Conclusions: Patients diagnosed with AGC‐NOS should undergo a careful evaluation with all clinicopathological features. Because cancer of the cervix and endometrium is not rare in patients diagnosed with AGC‐NOS, colposcopic examination with endocervical sampling should be a priority based on a cervicovaginal smear. Endometrial sampling is also required according to the patient's clinic, age, and examination characteristics. [ABSTRACT FROM AUTHOR]

The project named Victoria's cells was created to train health care personnel, especially in low‐income countries. This innovative approach is designed to associate benign and malignant cellular images and/or patterns with a range of shapes and color shades to evoke animals, common objects, and colorful aquariums. The project makes use of familiar images to capture the viewer's interest as an aid for cytological interpretation. Cervicovaginal cytology is processed with conventional and liquid‐based cytology. The images are visually compelling to highlight the importance of studying cells and their diagnostic significance. Infectious diseases as well as malignant cells are thereby easily recognized. The pictures are organized into different sections, including Victoria's zoo, Victoria's fantasy, and malignant mockery. Branching mycelia resemble a starfish; squamous metaplasia recalls a sea turtle's shell. Among others, different patterns of endometrial, endocervical, and squamous cells can resemble fish tanks populated by cells with the shapes of pufferfish, anglerfish, whales, scorpions, and garfish. The sea transitions to the earth, with a sly cat, a little elephant, a dog, and a koala. Other cellular preparations resemble a gymnast, a geisha, and a plunging diver as well as hummingbirds, a heron, a water lily, and a peony. The malignant mockery section is composed of squamous intraepithelial lesion patterns that resemble monsters, eyes, a foul tongue, eagles, and feathers. In conclusion, the recognition of visual images can make the study of cytology simpler and more enjoyable and serve the final objectives of prevention and cure. The recognition of visual images can make the study of cytology simpler and enjoyable and always leads to the final purpose of prevention and cure. [ABSTRACT FROM AUTHOR]

Background: Although the incidence of cervical adenocarcinoma has consistently increased, especially among young women, there is no established best means for screening. This study evaluated the screening efficacy of CINtec PLUS (CINtec; p16/Ki67 double immunocytochemistry) expression in cervical glandular cells. Methods: Cervical cytology was examined using abnormal glandular cells. The CINtec status of 100 samples with corresponding surgically resected specimens and 11 samples that exhibited negative results for intraepithelial lesion or malignancy at follow‐up was analyzed. Additionally, 31 negative samples containing benign glandular cells were included. Results: Of the 142 samples, CINtec status was diffusely positive in 74, focally positive in 24, and negative in 44. The 74 diffusely positive samples included 70 adenocarcinomas (62 cervical, seven uterine, and one ovarian) and four cases of high‐grade cervical intraepithelial neoplasia. The 24 focally positive samples included 15 adenocarcinomas (seven cervical, seven uterine, and one fallopian tube) and nine without malignancy. The 44 negative samples included nine adenocarcinomas (five uterine and four cervical) and 35 without malignancy. The sensitivity, specificity, positive predictive value, and negative predictive value of the CINtec diffusely or focally positive cases for cervical adenocarcinomas were 94.5%, 58.0%, 70.4%, and 90.9%, respectively. In CINtec diffusely positive cases, the respective values were 84.9%, 82.6%, 83.8%, and 83.8%, and in women aged ≤39 years the values were 90.6%, 89.5%, 93.5%, and 85.0%, respectively. Conclusions: CINtec may support efficient detection of cervical adenocarcinomas. CINtec PLUS cytology (p16/Ki‐67 double immunocytochemistry) can be used as triage for women with positive human papillomavirus and negative Papanicolaou results, with high specificity for the detection of high‐grade squamous intraepithelial lesions. This study reveals that CINtec PLUS cytology may also be applicable to the detection of cervical adenocarcinoma lesions. [ABSTRACT FROM AUTHOR]

To evaluate the risk of false HPV‐negative results and possible related morphological abnormalities in HPV primary cervical cancer screening. Out of 53,661 HPV‐negative cases, 5469 (10.2%) randomly selected cytology slides were evaluated as a part of the quality assurance protocol. The Bethesda category negative for intraepithelial lesion or malignancy (NILM) in the HPV‐negative cases given was present in 95.4%. Due to cytology other than NILM, 0.4% of cases were referred to colposcopy and 4.2% to the follow‐up in one year. In the follow‐up HPV negativity and NILM cytology was present in 88.3% of attended women. Cases other than HPV negative and NILM were referred to colposcopy. One biopsy‐proven histological HSIL was found in the first round and one in follow‐up screening. More comprehensive genotyping of HSIL cases revealed genotypes 69 and 11. Only two HPV test negative cases with histological HSIL were revealed forming 0.04% of quality control group. In both cases, HPV genotype not included in screening tests was found. According to the results, the primary HPV test with cytology triage is an efficient and specific method for cervical cancer screening despite of the fact that some non‐high‐risk genotypes are missed. [ABSTRACT FROM AUTHOR]

Introduction: Uterine clear cell adenocarcinoma (CCC) is a rare, aggressive malignancy with poor prognosis. The present study aimed to identify and describe its characteristic morphological features in cervical cytology. Methods: This was a 3‐year retrospective case‐control study. Cases included cervical samples of histopathologically proven endometrial and cervical CCC. Controls included cervical samples of histopathologically proven endometrial serous carcinoma (n = 15), endometrioid adenocarcinoma (n = 20), and endocervical adenocarcinoma (n = 15). Twenty‐eight cytomorphological features were evaluated; the strength of association was determined by odds ratio (OR) and Cramer's V, and the diagnostic accuracy of statistically significant features was assessed. Results: Cases consisted of histopathologically proven 25 (34.7%) endometrial and 13 (18.0%) cervical CCC. Corresponding cervical samples were available for a total of 14 (36.8%) patients, of which 13 (92.8%) were positive for epithelial cell abnormality. On univariate analysis, three cytomorphological variables were significant predictors of uterine CCC: presence of dense cytoplasm (OR = 88; V = 0.72), deep nuclear membrane irregularities (OR = 17.5; V = 0.55), and coarse chromatin (OR = 21.3; V = 0.46). Dense cytoplasm had the highest positive predictive value (92%) and high specificity (97.8%), whereas coarse chromatin had the highest sensitivity (92.3%) and negative predictive value (96.7%). Conclusions: The presence of dense cytoplasm and deep nuclear membrane irregularities in the tumour cells were strong predictors, and coarse chromatin a moderate predictor, of uterine CCC compared to its close cytological mimics. [ABSTRACT FROM AUTHOR]

Background: Although many cervical cytology diagnostic support systems have been developed, it is challenging to classify overlapping cell clusters with a variety of patterns in the same way that humans do. In this study, we developed a fast and accurate system for the detection and classification of atypical cell clusters by using a two‐step algorithm based on two different deep learning algorithms. Methods: We created 919 cell images from liquid‐based cervical cytological samples collected at Sapporo Medical University and annotated them based on the Bethesda system as a dataset for machine learning. Most of the images captured overlapping and crowded cells, and images were oversampled by digital processing. The detection system consists of two steps: (1) detection of atypical cells using You Only Look Once v4 (YOLOv4) and (2) classification of the detected cells using ResNeSt. A label smoothing algorithm was used for the dataset in the second classification step. This method annotates multiple correct classes from a single cell image with a smooth probability distribution. Results: The first step, cell detection by YOLOv4, was able to detect all atypical cells above ASC‐US without any observed false negatives. The detected cell images were then analyzed in the second step, cell classification by the ResNeSt algorithm, which exhibited average accuracy and F‐measure values of 90.5% and 70.5%, respectively. The oversampling of the training image and label smoothing algorithm contributed to the improvement of the system's accuracy. Conclusion: This system combines two deep learning algorithms to enable accurate detection and classification of cell clusters based on the Bethesda system, which has been difficult to achieve in the past. We will conduct further research and development of this system as a platform for augmented reality microscopes for cytological diagnosis. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to evaluate the clinical performance for detecting cervical intraepithelial neoplasia (CIN) 2 or higher lesions among available human papillomavirus infection (HPV) genotyping tests in Korea. Methods: Eligible patients visited 13 tertiary hospitals for colposcopic biopsy following cervical cytology and HPV genotyping test between January and December 2018. Baseline characteristics including age, body mass index (BMI), and parity were collected from 3798 patients. The performance of the Roche Cobas HPV 4800 was evaluated against other domestic HPV assays to detect CIN2 or higher. Results: A total of seven types of HPV genotyping tests were analyzed in the research institutes. A total of 1358 patients (35.8%) tested Anyplex II HPV 28 and 701 patients (18.5%) tested Cobas 4800 HPV. The overall sensitivity in the detection of CIN2 or higher was 41.5% (38.9–44.1) in patients positive for HPV 16/18. The Cobas test for HPV 16/18 was concordant with other assays evaluated for detection of CIN2 or higher and showed sensitivity of 46.6%, which was not significantly different from other assays. Although Anyplex II HPV28 (Seegene) showed slightly decreased sensitivity for detecting CIN2 or higher lesion with HPV 16/18 positive (39.8%, p < 0.05) compared to Cobas 4800, in aspect of high‐risk HPV positive, Anyplex II HPV28 showed increased sensitivity (96.9%, p < 0.05). Conclusion: The performance of the HPV genotype test that were commonly used in Korea was concordant with Cobas HPV test. Further studies are needed to evaluate the safety, efficiency, and cost‐effectiveness of the various commercially available domestic HPV assays. [ABSTRACT FROM AUTHOR]

Small cell neuroendocrine carcinoma (SCNEC) of the cervix is a rare, highly aggressive tumour with poor prognosis and high propensity for distant metastases. The cytological features of SCNEC have rarely been described in cervical samples, and to the best of our knowledge, there are no previous reports using SurePath™ liquid‐based cytology. In the present report we present the cytomorphological features of histopathologically confirmed cases of cervical SCNEC in SurePath preparations. On cytological examination, all three cases demonstrated variable numbers of tumour cells, ranging from a few dispersed cells and tiny micro‐biopsies to large aggregates of small tumour cells with a high nucleus‐to‐cytoplasmic ratio, stippled chromatin, inconspicuous nucleoli, and scant cytoplasm. Immunocytochemistry for CD56 on the cervical preparation confirmed the diagnosis in one case. The presence of small tumour cells with characteristic stippled/salt‐and‐pepper type nuclear chromatin were the most consistent cytological features in these cases. Knowledge of these characteristic cytological features can help in suggesting a diagnosis of SCNEC in cervical samples which can then be confirmed by immunocytochemistry. [ABSTRACT FROM AUTHOR]

Introduction: Cervical cytology is a well‐stablished cervical cancer screening method. However, due to the anatomical continuity of the genital tract, it can also detect signs of endometrial disease. Our aim was to estimate the sensitivity of cervical cytology in endometrial cancer detection and prognosis in a large population over a 30‐year period in a large academic tertiary hospital in Spain. Methodology: We performed a search for women diagnosed with endometrial cancer from 1990 to 2020, who were surgically treated and had a previous cervical cytology result. Information Technologies Department databases from Bellvitge University Hospital and the Screenwide case–control study's database were used. Cervical cytology results were classified as abnormal when squamous lesions, glandular atypia or malignant cells were identified. Results: Overall, we evaluated 371 women with endometrial cancer and a documented cervical cytology performed within 3 years previous to surgical treatment. Overall, the sensitivity of cervical cytology for endometrial cancer detection was 25.6%. Several clinico‐pathological characteristics, such as non‐endometrioid histology and a higher stage, were correlated with higher sensitivity. Discussion: We observed a low sensitivity of cervical cytology to effectively diagnose endometrial cancer. However, recent technological advances using genomics and epigenomics may offer a promising perspective to detect endometrial cancer with high sensitivity in these cervical specimens. [ABSTRACT FROM AUTHOR]

The cervical cytology of our patient transformed from squamous cell carcinoma to negative for intraepithelial lesion or malignancy, possibly due to the graftversus-tumor effect following allogeneic stem cell transplantation. [ABSTRACT FROM AUTHOR]

Objective: Cervical cancer screening by primary human papilloma virus detection and cytology is fraught with low specificity and variable sensitivity, respectively. Cytology‐histology correlation remains modest. Biomarkers associated with early genetic events in cervical squamous carcinogenesis and detectable in cytology material are likely to be relevant. Human telomerase RNA component (hTERC) gene overexpression and aneuploidy are promising candidates in view of their reported early and consistent association with cervical squamous oncogenesis. Methods: We analysed hTERC gene expression and chromosome 7 ploidy by fluorescent in‐situ hybridisation (FISH) in 50 women with cytological precursor squamous intraepithelial lesions and available histology outcomes. Results were expressed as percentages of cells showing ≥3 signals, mean signals/nucleus, and maximum amplitude across various cytology and histology categories. Proportions of positive cases were calculated from threshold values derived from 6 controls. Distribution of above indices with respect to ≥cervical intraepithelial neoplasia 2 (CIN2) was explored. Results: For both genetic aberrations, there was significant positive correlation (for all indices) between the proportion of positive cases and worsening cytological and histological outcomes (P <.05), with significant intergroup differences (P <.05). High‐grade lesions (≥CIN2) had significantly higher results compared to

BACKGROUND: Cervical cytology screening is usually laborious with a heavy workload and poor diagnostic consistency. The authors have developed an artificial intelligence (AI) microscope that can provide onsite diagnostic assistance for cervical cytology screening in real time. METHODS: A total of 2167 cervical cytology slides were selected from a cohort of 10,601 cases from Shenzhen Maternity and Child Healthcare Hospital, and the training data set consisted of 42,073 abnormal cervical epithelial cells. The recognition results of an AI technique were presented in a microscope eyepiece by an augmented reality technique. Potentially abnormal cells were highlighted with binary classification results in a 10× field of view (FOV) and with multiclassification results according to the Bethesda system in 20× and 40× FOVs. In addition, 486 slides were selected for the reader study to evaluate the performance of the AI microscope. RESULTS: In the reader study, which compared manual reading with AI assistance, the sensitivities for the detection of low‐grade squamous intraepithelial lesions and high‐grade squamous intraepithelial lesions were significantly improved from 0.837 to 0.923 (P <.001) and from 0.830 to 0.917 (P <.01), respectively; the κ score for atypical squamous cells of undetermined significance (ASCUS) was improved from 0.581 to 0.637; the averaged pairwise κ of consistency for multiclassification was improved from 0.649 to 0.706; the averaged pairwise κ of consistency for binary classification was improved from 0.720 to 0.798; and the averaged pairwise κ of ASCUS was improved from 0.557 to 0.639. CONCLUSIONS: The results of this study show that an AI microscope can provide real‐time assistance for cervical cytology screening and improve the efficiency and accuracy of cervical cytology diagnosis. In this study, an artificial intelligence microscope has been developed that can provide real‐time assistance for cervical cytology screening. This artificial intelligence microscope can improve the efficiency and accuracy of cervical cytology diagnosis. [ABSTRACT FROM AUTHOR]

Introduction: Human papillomavirus (HPV) is the causative agent of precancerous lesions and cervical cancer, cervical cancer being the leading cause of deaths in Tanzanian women. Early detection and treatment of precancerous lesions are important in the prevention of cervical cancer cases. Material and methods: We conducted a cross‐sectional study among 3390 Tanzanian women aged 25‐60 years. Information on lifestyle habits was collected, and women underwent gynecological examination with collection of cervical cells for conventional cytological and HPV testing. Blood samples were tested for HIV. The association between cervical high‐grade cytology (HGC) and potential risk factors was examined using multivariable logistic regression adjusting for age and high‐risk HPV (HR‐HPV). Results: The prevalence of HGC was 3.6% and of low‐grade cytology was 8.3%. In women who were both HR‐HPV‐positive and HIV‐positive, the prevalence of HGC was 28.3%. It increased by age and was 47% among women aged 50‐60 years. Women, who had their sexual debut at age 9‐15 years and 16‐18 years, respectively, had 2.5 and 2.4 times increased odds of HGC compared with women whose sexual debut was at age 21 years and older. HIV‐positive women had increased odds of HGC in comparison with HIV‐negative women after adjustment for age (odds ratio [OR] 2.95, 95% CI 1.92‐4.54). HR‐HPV‐positive women had nearly 100‐fold increased odds of HGC compared with HR‐HPV‐negative women (OR 96.6, 95% CI 48.0‐194), and this estimate was higher among HIV‐positive women (OR 152.2, 95% CI 36.1‐642.0). Conclusions: Increasing age, early age at first intercourse, HR‐HPV, and HIV infections were associated with a substantially increased risk of HGC. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV) genotype testing has limited utility to identify human immunodeficiency virus‐infected (HIV+) women's risk for developing cervical cancer (CC) due to high positivity rate of high‐risk (HR) HPVs. We investigated the accuracy of HPV testing in isolation/in combination with CD4 and HIV viral load (VL) to identify HIV+ women at risk for developing CC. Methods: Study consisted of 344 HIV+ women on combination antiretroviral therapy (cART), tested for cervical cytology/HPV using the Cobas test and had data on absolute CD4 count and VL measurements. We calculated the positive predictive value (PPV) and negative predictive value (NPV) of HPV testing, pre‐, post‐cART, and current CD4 and VL in isolation and in combinations to identify those with or free of higher than atypical squamous cells of unknown significance (ASCUS+) or low‐grade intraepithelial lesions (LSIL+). Results: HPV test in combination with pre‐/post‐cART or current CD4 counts and VL had higher PPVs compared to HPV test alone for identifying ASCUS+ or LSIL+. PPV of HPV‐CD4 combinations yielded higher PPVs compared to HPV‐VL combinations. The NPVs with pre‐, post‐cART, or current CD4 count and VL in isolation or in combinations were comparable to that of HPV test alone. Conclusions: Our results provide a more accurate tool for managing HIV+ women by combining Cobas HPV with CD4 and VL, especially those who had an undesirable pre‐cART CD4 and VL status. Our results also indicate the usefulness of CD4 and VL measurements to identify those at lower risk in the absence of HPV testing. [ABSTRACT FROM AUTHOR]

Introduction: Gastric‐type endocervical adenocarcinoma (GAS) is an uncommon type of endocervical adenocarcinoma that is not associated with human papillomavirus infection. This diagnosis is relatively rare and may portend a worse prognosis than usual‐type endocervical adenocarcinoma. Subtle morphological features make it an under‐recognised diagnostic challenge. Study of the cytological features of individual cases is valuable in order to increase awareness of this entity. Methods: The pathology database of our institution was searched for the diagnosis of GAS and all cytological and surgical specimens for each patient were reviewed. The original cytological interpretation was compared to a retrospective central review interpretation. Clinical history and follow‐up results were obtained from the electronic medical record. Results: Four cases of GAS were identified. The findings on initial cervical cytology varied, with GAS found in both patients with negative cervical cytology and those with atypical glandular cells. Cytological findings included endocervical cells arranged in three‐dimensional clusters and honeycomb sheets with abundant vacuolar cytoplasm, and in two patients, moderate nuclear atypia with irregular nuclear membranes, coarse chromatin, hyperchromatic nuclei, and prominent nucleoli. In one patient, GAS was incidentally discovered via thorough sampling of a cystic lesion in the superior portion of the endocervical canal. Conclusions: GAS is an aggressive human papillomavirus‐independent type of endocervical adenocarcinoma with subtle morphological features and, as our study shows, varying clinical presentation. Given the aggressive nature of GAS and the difficulties in initial diagnosis, increased awareness of this entity among pathologists is crucial. Gastric‐type endocervical adenocarcinoma (GAS) is an uncommon type of endocervical adenocarcinoma that is not associated with human papillomavirus infection. Four cases of GAS are presented, and findings in cervical cytology are reviewed and compared to those described in the literature. [ABSTRACT FROM AUTHOR]

An unusual case is described of a 64‐year‐old woman with a remote history of breast cancer whose first non‐nodal metastasis was discovered on a routine Pap test. The Pap test was supported by the results of cervical and endometrial biopsies. [ABSTRACT FROM AUTHOR]

Objective: To describe prevalent and persistent oncogenic human papillomavirus (HPV) types detected in women living with HIV (WLWH) in Canada, including women with cervical dyskaryosis, and to determine predictors of type-specific HPV persistence.Methods: Women and girls living with HIV, recruited from 14 sites of HIV care across Canada, were included in a sub-analysis of a prospective vaccine immunogenicity cohort study (two HPV DNA results, at least one cervical cytology result pre-vaccination). Demographic and clinical data were collected alongside cervical samples for cytology and HPV DNA typing between November 25, 2008, and May 19, 2015.Results: Pre-vaccination, HPV16 and HPV52 were the most prevalent oncogenic HPV types. Of the 252 women and girls who met the eligibility criteria, 45% were infected with at least one oncogenic HPV type and one-third of participants had a persistent oncogenic infection. HPV16, 45, and 52 were the most frequently persistent types. Seventeen percent of women had persistent infections with oncogenic HPV types not within currently available vaccines (HPV35/39/51/56/59/68/82). Lower CD4 count significantly predicted HPV persistence (P=0.024). Cervical cytology results were normal for 82.9% of participants, atypical squamous cells of undetermined significance for 2.4%, low-grade squamous intraepithelial lesions for 11.5%, and high-grade squamous intraepithelial lesions for 2.8%.Conclusion: Unvaccinated WLWH were infected with a wide range of oncogenic HPV types. The findings highlighted the importance of optimal treatment of HIV and continued cervical cancer screening as key steps toward the global elimination of cervical cancer. [ABSTRACT FROM AUTHOR]

Background: The scarcity of updated data on the prevalence of cervical human papillomavirus (HPV) infection in the Gulf Cooperation Council (GCC) countries hampers the establishment of cervical cancer screening and HPV vaccination programs. The current study estimated the prevalence of cervical high‐risk (HR) HPV infection among women residing in some countries of the GCC and analyzed the correlation between HR‐HPV infection types and cytology results. Methods: In total, 2478 women residing in the Kingdom of Saudi Arabia, Qatar, the United Arab Emirates, and Bahrain were enrolled in this study. Cervical specimens were subjected to simultaneous liquid‐based cytology and HR‐HPV DNA analysis. Results: Of 2478 women, 520 (21%) tested positive for HR‐HPV. Other non‐HPV genotype 16 (HPV16)/HPV18 HR‐HPV was the most frequently detected infection type, accounting for 63.7%. Non‐Arab women had a significantly higher HR‐HPV positivity rate compared with Arab women (31.6% vs 16.4%; P < .001). The HR‐HPV positivity rate was highest among women residing in Qatar (31.3%), followed by women living in Bahrain (20%), the Kingdom of Saudi Arabia (17.2%), and the United Arab Emirates (14.7%). The overall prevalence of HR‐HPV infections declined significantly with advancing age (P < .001). Women with abnormal cytology had a significantly higher HR‐HPV positivity rate than those with normal cytology (50.6% vs 14.7%; P < .001). The HR‐HPV positivity rate increased as the severity of the cytological lesion increased. Conclusions: The current study provides updated data on HR‐HPV prevalence in the GCC countries and delivers an evidence base for supporting the introduction of regional/national vaccination and screening programs in these countries. This study provides reliable epidemiological data related to human papillomavirus (HPV) type‐specific distribution among women residing in the Gulf Cooperation Council countries and delivers a robust evidence base for supporting the introduction of regional and/or national HPV vaccination and HPV‐based cervical cancer screening programs in the Gulf Cooperation Council countries. [ABSTRACT FROM AUTHOR]

Background: For Australian women with screen‐detected adenocarcinoma‐in‐situ (AIS), an excisional biopsy is mandatory for further assessment, treatment, and to exclude the presence of cervical adenocarcinoma. The only exclusion to this rule is if the woman has a clinically evident invasive cervical malignancy. Excisional treatments should be tailored according to a patient's age and future obstetric needs. To date, practitioner compliance with this recommendation has not been investigated. Aims: To investigate clinical management for patients with a cytological test result predicting AIS. Secondary aims were to report the most severe histological findings of excisional biopsy specimens following cytological prediction of AIS and investigate treatment outcomes for conservatively managed patients with biopsy‐confirmed AIS. Materials and Methods: A retrospective, population‐based cohort study was conducted. Cases were ascertained from the Tasmanian and Western Australia Cervical Screening Registries. Cytology and histology results for women with an index cervical smear reporting AIS from 2001 to 2012 were reviewed. Results: Three hundred and twenty‐one women (age range 18–69 years) had an index smear reporting AIS. Cervical cancer was diagnosed in 62 (19.3%) patients within the study cohort. Twenty‐one of 321 patients (6.7%) were not initially managed according to the 2005 NHMRC Guidelines for the management of asymptomatic women with screen‐detected abnormalities, including two women diagnosed with an occult cancer following a total hysterectomy. Conclusions: A minority of women were not managed in accordance with guidelines. This is of concern given that nearly one in five women with a smear predicting AIS had a final diagnosis of cervical cancer. [ABSTRACT FROM AUTHOR]

Objective: Peer review of equivocal/abnormal Papanicolaou smears is a standard internal quality assurance measure in cervical cancer screening laboratories. In 2014, we introduced a new method for peer review involving blinding the identity of the first reader. We present the comparison of different measures of inter‐reader agreement in 2013 and 2014 in order to measure the impact of blind peer review on possible cognitive biases in reading. Methods: All suspect slides are proposed for peer review; a single reader's peer reviews are registered independently, with discordant cases discussed for consensus diagnosis. Since 2014, the first reader's name has been blinded to peers. We computed how frequently the initial diagnosis was changed, and how frequently a single reader influenced the final diagnosis when the initial one was changed. We compared κ of the first reader and that of other readers with final diagnosis. Data from 2013 were compared to those of 2014. Results: The final diagnosis changed in 22.9% of cases (range 16.8%‐34.4%) in 2013 and in 26.8% (range 13.9%‐35.6%) in 2014 (P = .2). Individual peer diagnoses agreed with final diagnosis in 52.3% (range 41.9%‐66.3%) in 2013 and in 50.2% (range 36.0%‐65.8%) in 2014 (P =.55). The cytologist having the highest proportion of confirmed diagnoses was also the most influential on final diagnosis, both in 2013 and in 2014. Agreement between first reader and final diagnosis was higher than that of each reader in 2013 and in 2014. Conclusions: Blinding the identity of the first reader had little or no impact on inter‐reader agreement measures in our laboratory. Peer review of equivocal/abnormal Pap smears is a standard internal quality assurance measure in cervical cancer screening laboratories. This study compares different measures of inter‐reader agreement in a period when the identity of first reader was known (2013) and when it was blinded to other readers (2014) to measure the impact of blind peer review on possible cognitive biases in reading. The authors found that, in their laboratory, blinding the identity of the first reader had little or no impact on inter‐reader agreement. [ABSTRACT FROM AUTHOR]

Background: The p16 immunohistochemical (IHC) marker has been used increasingly as an adjunct to morphologic assessment of cervical biopsies in which the differential diagnoses include high‐grade squamous intraepithelial lesion (HSIL) and its mimics. The objective of this study was to assess the potential influence of p16 IHC staining on the evaluation of cervical biopsy as observed through cytologic‐histologic correlation (CHC). Methods: Cervical biopsy samples that had cytologic diagnoses of either low‐grade squamous intraepithelial lesion (LSIL) or HSIL and also had histologic follow‐up were retrieved from the department database. CHC and the use of p16 IHC from 2 periods (group 1, 2008; group 2, 2014‐2016) were compared and analyzed. Results: Histology on 452 samples from patients who had prior LSIL cytology in group 1 yielded 126 benign (27.9%), 272 LSIL (60.2%), and 54 HSIL (11.9%) diagnoses. By comparison, 491 samples from the patients in group 2 yielded 106 benign (21.6%), 277 LSIL (56.4%), and 108 HSIL (22.0%) diagnoses. The difference in CHC discrepancies between the 2 groups was significant (P =.0001), mainly because of the increased diagnosis of HSIL in group 2. Although p16 IHC was not applied to any sample from group 1, it was performed on 141 of 491 samples (28.7%) from group 2. Further follow‐up of patients who had histologic HSIL revealed that residual HSIL was identified significantly more often in those who did not have p16 IHC applied in the preceding cervical biopsy than in those did (P =.0004). A similar comparison was performed between 113 patients from group 1 and 152 patients from group 2 who had a prior diagnosis of HSIL cytology, and the difference was statistically insignificant. Conclusions: The use of p16 IHC on cervical biopsies in patients who had a prior cytologic diagnosis of LSIL may lead to greater detection and upgrading of HSIL, thereby compounding the discrepancy in CHC. The potential influence of p16 immunohistochemical staining on the assessment of cervical biopsies is evaluated using results from cytologic‐histologic correlation. The findings indicate that, on cervical biopsy specimens with a previous cytologic diagnosis of low‐grade squamous intraepithelial lesion, p16 immunohistochemistry may lead to an increase in the detection and upgrading of high‐grade squamous intraepithelial lesion. [ABSTRACT FROM AUTHOR]

4vHPV vaccination has been tested in randomized controlled trials under almost ideal conditions, and studies of real‐life use have compared outcome between vaccinated and unvaccinated women from the same birth cohort and mostly before screening age. Here we present the first—to our knowledge—evaluation of the impact of the 4vHPV vaccination in real life without selection bias in the reported data. The study has been carried out by comparing the results after first cervical screening between an HPV‐vaccinated and an unvaccinated birth cohort, consisting of women born in Denmark in 1993 and 1983, respectively. Cytology data covering an 8‐year period, from the age of 15 (age of HPV‐vaccination) to age 23 (age of invitation to first cervical screening), were retrieved from the Danish National Pathology Register. Abnormal cytology, defined as atypical squamous cell of undetermined significance and worse (ASCUS+) was detected in 9.4% of women born in 1993 as compared with 9.0% of women born in 1983; RR = 1.04 (95% CI 0.96–1.12), p = .29. Detection of high‐grade squamous intraepithelial lesion (HSIL) was statistically significantly lower in the 1993 than in the 1983 cohort, RR = 0.6 (95% CI 0.5–0.7), p < .0001, while the opposite pattern was seen for ASCUS RR = 1.4 (95% CI 1.2–1.6), p < .0001. The decrease in HSIL means that more women can be spared referral for colposcopy and biopsy. The increase of ASCUS could be explained by transition from conventional to liquid‐based cytology, but this observation requires further monitoring. [ABSTRACT FROM AUTHOR]

BACKGROUND: In situ hybridization for human papillomavirus (HPV) messenger RNA (HPV RNA ISH) recently was introduced as an ancillary tool in the diagnosis of cervical squamous intraepithelial lesions, and can aid in the distinction between low‐grade squamous intraepithelial lesions (LSILs) versus reactive/negative biopsies. Prior work has shown that up to one‐half of cases originally diagnosed as LSIL are reclassified as negative/reactive by expert consensus review of morphology, and negative HPV RNA ISH results most often correlate with an expert diagnosis of negative/reactive. Given that LSIL overdiagnoses on biopsy may result in the erroneous clinical impression that a cervical lesion has been sampled appropriately, the authors proposed that HPV RNA ISH can inform cytology‐histology correlation for challenging LSIL biopsies. METHODS: A total of 92 cervical biopsies originally diagnosed as LSIL were reviewed by 3 gynecologic pathologists and reclassified based on consensus opinion of morphology. ISH was performed for high‐risk and low‐risk HPV E6/E7 mRNA. Prior/concurrent cytology results were collected. RESULTS: Based on expert consensus morphologic review, 49% of biopsies (45 of 92 biopsies) originally diagnosed as LSIL were reclassified as negative, 6.5% (6 of 92 biopsies) were reclassified as high‐grade squamous intraepithelial lesion, and 44.5% (41 of 92 biopsies) were maintained as LSIL. The majority of LSIL biopsies reclassified as negative (80%; 36 of 45 biopsies) were HPV RNA negative, whereas 93% of LSIL biopsies (39 of 41 biopsies) and 100% of high‐grade squamous intraepithelial lesion biopsies were HPV RNA positive. CONCLUSIONS: LSIL often is overdiagnosed by morphology on biopsy, potentially leading to the false impression that a lesion identified on cytology has been sampled. Performing RNA ISH on biopsies decreases histologic LSIL overdiagnosis, and potentially can prompt further sampling when there is cytology‐histology discordance. Cancer (Cancer Cytopathol) 2018. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Introduction: Primary HPV screening will be implemented into the English Cervical Screening Programme by 2019. Its impact upon women referred to colposcopy, with negative cytology but persistently positive high‐risk HPV (hrHPV), remains unreported from UK Sentinel sites. HPV primary screening was introduced in Sheffield, UK in April 2013; this paper reports its impact on the service. Methods: A retrospective cohort study was performed from June 2014 to July 2016 at the Jessop Wing Colposcopy Unit, Sheffield. UK. Data were obtained from the pathology and colposcopy databases and cross‐referenced with case‐notes and pathology results for women referred with persistently positive hrHPV, cytology negative samples. Patient demographics, hrHPV genotype, biopsy rates, histological diagnoses, management, and outcomes were collected and baseline statistics performed. Results: During the study 1076 women were seen. Most frequent hrHPV genotypes were: hrHPV other, 41%; and HPV16, 33%. The majority (72%) were found to have normal colposcopy; 28% had an abnormal colposcopic assessment (11% low‐grade; 11% high‐grade; 6% inadequate). The majority were discharged (83%) and only 5% underwent LLETZ. No cancers were detected. High‐grade cervical intraepithelial neoplasia (CIN) was found in 7%; overall risk of CIN2 was 1/29; 1/30 for CIN3. Presence of HPV16 was associated with a significantly higher risk of high‐grade CIN; 1/9. Conclusion: This is the first study to report results for women referred to colposcopy with cytology negative, persistently positive hrHPV. Disease prevalence is low, although women with HPV16 have a significantly higher likelihood of high‐grade disease compared to other HPV subtypes. [ABSTRACT FROM AUTHOR]

Introduction: Abnormal cervical cytology in patients with endometrial cancer (EC) has been associated with poor outcome. The aim of this study was to evaluate whether cervical cytology could contribute to an improved preoperative identification of high‐grade EC (serous, clear cell, carcinosarcoma, high‐grade endometrioid EC) in final histology. Methods: A retrospective cohort study was performed in five hospitals in the Netherlands. A total of 554 patients with EC that underwent primary surgical treatment between 2002 and 2010 were included. Primary outcome was defined as the contribution of abnormal cervical cytology in the preoperative identification of high‐grade EC. As secondary outcome, recurrence‐free survival (RFS) and disease‐specific survival were determined based on preoperative cervical cytology, and compared to the currently established risk factors: myometrial invasion, high‐grade and lymph vascular space invasion. Results: Abnormal cervical cytology was present in 45.1%. For patients with preoperative inconclusive and high‐grade histology, the presence of abnormal cervical cytology contributed to an improved identification of high‐grade EC in final histology (odds ratio [OR] 6.40 [95% confidence interval {CI}: 1.92‐21.26]; OR 2.86 [95% CI: 1.14‐7.14]), respectively. Patients with abnormal cervical cytology had a significant worse 5‐year median RFS. Abnormal cervical cytology was independently related to RFS (hazard ratio 1.67 [95% CI: 1.04‐2.68]) and disease‐specific survival (hazard ratio 3.15 [95% CI: 1.74‐5.71]). Conclusions: Abnormal cytology contributes to the preoperative identification of patients with high‐grade EC, and is associated with compromised outcome. Future studies are warranted to determine whether cervical cytology could be incorporated into preoperative prediction models for lymph node metastasis. [ABSTRACT FROM AUTHOR]

Cytology-based cervical cancer screening is restricted because of a lack of cytologists. Thus, HPV-based instead of cytology-based screening may be a more suitable strategy in China. Here, we assessed the effectiveness of HPV testing (Cobas® 4800 Test, Roche) and HPV-based programs to detect high-grade cervical intraepithelial neoplasia ( CIN) or cancer compared with cytology (Thinprep, Hologic) and cytology-based programs through a cross-sectional study in 11,064 Chinese women aged 21-65 years who were enrolled from Longyou County in Zhejiang Province, China. The rates of HPV positivity and cytology abnormality were 9.8% and 6.1%, respectively. The HPV positivity rate had two age peaks, 21-24 (15.4%) and 60-65 (14.4%) years. According to adjusted data, HPV testing demonstrated significantly higher sensitivity and negative predictive value ( NPV) than cytology for detecting CIN2 or worse (90.0% vs. 66.7%, 99.9% vs. 99.5%), and there was an acceptable specificity (91.3%) and positive predictive value ( PPV, 12.5%). Furthermore, primary HPV testing with type 16/18 genotyping showed the highest sensitivity (78.6%) and NPV (99.7%) among four screening strategies, and there was similar specificity (96.8%) and PPV (23.9%) compared with co-testing screening to detect CIN2+, while there were fewer colposcopies (4.2) and tests (106.3) performed than with co-testing and primary cytology screening to detect a case of high-grade CIN. The differences in effectiveness were approximately similar when CIN3+ was the identifying target. Our findings suggest that primary HPV testing with type 16/18 genotyping has a higher sensitivity and NPV, possesses optimal cost/effectiveness in the first round of screening and is a feasible strategy of cervical cancer screening for Chinese women. [ABSTRACT FROM AUTHOR]

Zika virus ( ZIKV) infection during pregnancy has been linked to severe birth defects, and the epidemiologic situation of the ZIKV epidemic in Ecuador is poorly understood. Guayaquil, Ecuador, has a tropical climate and experiences frequent outbreaks of dengue and chikungunya virus, and in December 2015, ZIKV was identified. Given the well-documented effects of ZIKV in pregnancy, including microcephaly, we tested for the presence of ZIKV in both plasma and cervical cytology of pregnant women. We report the identification of a population of pregnant women with a high incidence of ZIKV infection detected in the plasma and lower reproductive tract. A case-control study was performed to determine the incidence of ZIKV infection among low-income, pregnant women at risk for preterm delivery compared to matched controls. Plasma and cervical cytology specimens were tested for ZIKV by rRT- PCR. Fifty-nine pregnant women were enrolled. The incidence of ZIKV was 54% (32/59) overall: 18/31 (58.1%) in cases and 14/28 (50.0%) in controls. ZIKV detection in plasma and cervical cytology specimens demonstrated good agreement. Overall, outcomes for neonates born to ZIKV-positive and ZIKV-negative mothers were similar. However, two neonates were born with microcephaly to case mothers who were ZIKV positive. We report a high incidence of ZIKV infection (54%) in a distinctive population in Guayaquil, Ecuador. We identify ZIKV in cervical samples that correlates with ZIKV in the plasma. These data raise concerns regarding the breadth of the ZIKV epidemic in Ecuador and demonstrate the utility of cervical cytology specimens for ZIKV testing. [ABSTRACT FROM AUTHOR]

Women treated for high-grade cervical intraepithelial neoplasia (CIN) are at risk of recurrent CIN Grade 2 or worse (rCIN2+). Currently, posttreatment monitoring is performed using cytology or cytology/high-risk (hr)HPV cotesting. This study aimed to evaluate the performance of p16/Ki-67 dual-stained cytology (p16/Ki-67) for posttreatment monitoring. Three hundred and twenty-three women treated for high-grade CIN in the SIMONATH study underwent close surveillance by cytology, hrHPV and DNA methylation marker testing up to 12 months posttreatment. Histological endpoints were ascertained by colposcopy with biopsy at 6 and/or 12 months. p16/Ki-67 dual-staining was performed on residual liquid-based cytology samples obtained at, or shortly before biopsy collection. Clinical performance estimates of cytology, hrHPV, p16/Ki-67 testing and combinations thereof for the detection of rCIN2+ were determined and compared to each other. Sensitivity of p16/Ki-67 for rCIN2+ (69.2%) was nonsignificantly lower than that of cytology (82.1%; ratio 0.84, 95% CI: 0.71-1.01), but significantly lower than that of hrHPV testing (84.6%; ratio 0.82, 95% CI: 0.68-0.99). Specificity of p16/Ki-67 for rCIN2+ (90.4%) was significantly higher compared to both cytology (70.8%; ratio 1.28, 95% CI: 1.19-1.37) and hrHPV testing (76.2%; ratio 1.19, 95% CI: 1.12-1.26). Overall, hrHPV testing showed very high sensitivity, along with a good specificity. When considering cotesting, combined p16/Ki-67/hrHPV testing showed rCIN2+ sensitivity comparable to cytology/hrHPV cotesting (87.2% vs. 89.7%; ratio 0.97, 95% CI: 0.92-1.03), but with significantly increased specificity (74.2% vs. 58.1%; ratio 1.28, 95% CI: 1.19-1.38). Thus, when considered in combination with hrHPV, p16/Ki-67 might be an attractive approach for surveillance of women treated for high-grade CIN. [ABSTRACT FROM AUTHOR]

Cervical cancer screening based on the Papanicolaou (Pap) test is a widely applied but not always efficient practice for detecting Human Papillomavirus (HPV) mediated lesions, partially due to a non-systematic and inadequate screening process. Our aim was to introduce an inexpensive easy-to-use direct screening platform for improved detection of abnormal cells indicative of underlying cervical neoplasia as well as persisting HPV infection. By employing a novel, efficient technique of laser-based micromachining, we achieved the fabrication of spatial grids on commercially available coverslips allowing visual segmentation of the slide for efficient screening. Abnormal and formerly diagnosed as negative for intraepithelial lesion or malignancy (NILM) Pap test slides ( n = 200) were analyzed by conventional and grid-based screening. Grid-based microscopy led to a more reliable diagnosis compared to the conventional by identifying an increased number of abnormal cells ( P = 0.001). It decreased borderline ASCUS, AGC diagnosis, increasing LSIL, HSIL and in situ AdenoCa detection rates closely related with biopsy ( P = 0.015; kappa = 0.978). Concerning the set of NILM diagnoses in rapid re-screening, the method upgraded six cases ( n = 6) to LSIL ( P = 0.001). The proposed technical solution offers a calibration and orientation visual aid during the on-site screening process providing significant advantages compared to expensive digital imaging techniques. [ABSTRACT FROM AUTHOR]

Objective The 2001 Bethesda System for Reporting Cervical Cytology includes documenting 'endometrial cells in women ≥40 years of age' (E40) to help identify endometrial carcinoma ( EC) on a Papanicolaou (Pap) test. The 2014 Bethesda System for Reporting Cervical Cytology raises the threshold to ≥45 years of age (E45). As many of these women are menstruating, routine biopsy after E40, or even E45, may lead to unnecessary procedures for benign endometrial cells. Establishing a different age threshold in combination with other clinical findings may help to guide management. Methods A retrospective chart review was performed on consecutive EC specimens and E40 Pap tests. Clinical, pathological data such as age, biopsy diagnosis, FIGO grade and the time of the last Pap test, Pap test diagnosis and resection diagnosis, depth of invasion, stage and metastases were recorded. Results Sixty-three EC cases had prior Pap smears, with the following diagnoses: negative for an intraepithelial lesion or malignancy ( n = 27), atypical glandular cells, not otherwise specified (AGC, NOS) ( n = 14), adenocarcinoma ( n = 10) and E40 ( n = 1; 51 years). Six hundred and forty-two E40 cases had 138 (21.5%) biopsies and/or hysterectomies. Out of the 138 cases, two (1.4%) had EC (both 51 years; postmenopausal), one had complex hyperplasia with atypia (52 years; abnormal uterine bleeding), and eight had hyperplasia without atypia. Conclusions In asymptomatic women less than 50 years, E40 correlated with benign, non-hyperplastic endometrium. However, post-menopausal women with E40 had a risk of EC. Perhaps endometrial cells should only be reported in post-menopausal women or women greater than or equal to 50 years of age. [ABSTRACT FROM AUTHOR]

Objective To assess the sensitivity, the number needed to screen ( NNS) and the positive predictive value ( PPV) of cervical cytology for the diagnosis of cancer by age in a screening population. Methods A retrospective cohort of women with invasive cervical cancer nested within a census of cervical cytology. All ( c. 8 million) women aged 20-64 years with cervical cytology (excluding tests after an earlier abnormality). From April 2007 to March 2010, 3372 women had cervical cancer diagnosed within 12 months of such cytology in England. The sensitivity of cervical cytology to cancer, NNS to detect one cancer and predictive values of cytology were calculated for various 'referral' thresholds. These were calculated for ages 20-24, 25-34, 35-49 and 50-64 years. Results The sensitivity of at least moderate dyskaryosis [equivalent to a high-grade squamous intraepithelial lesion ( HSIL) or worse] for cancer of 89.4% [95% confidence interval (CI) 88.3-90.4%] in women offered screening was independent of age. At all ages, women with borderline-early recall or mild dyskaryosis on cytology (equivalent to ASC- US and LSIL, respectively, in the Bethesda system) had a similar risk of cervical cancer to the risk in all women tested. The PPV of severe dyskaryosis/?invasive and ?glandular neoplasia cytology (equivalent to squamous cell carcinoma and adenocarcinoma/adenocarcinoma in situ, respectively, in the Bethesda System) were 34% and 12%, respectively; the PPV of severe dyskaryosis (HSIL: severe dysplasia) was 4%. The NNS was lowest when the incidence of cervical cancer was highest, at ages 25-39 years, but the proportion of those with abnormal cytology who have cancer was also lowest in younger women. Conclusions The PPV of at least severe dyskaryosis (HSIL: severe dysplasia) for cancer was 4-10% of women aged 25-64 years, justifying a 2-week referral to colposcopy and demonstrating the importance of failsafe monitoring for such patients. The sensitivity of cytology for cervical cancer was excellent across all age groups. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Produced by the British Association for Cytopathology October 2015. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) infection is an important cause of cervical cancer. Screening with cytology or combined cytology and HPV testing helps to detect early cervical cancers and precancerous lesions (high-grade squamous intraepithelial lesion or worse [HSIL+]). Minor cytological abnormalities (atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion) account for the majority of abnormal cervical cytology results, but only 10-20% of women with minor cytological abnormalities have histologic HSIL+. Triage tests are useful to identify the high-risk patients and reduce the colposcopy burden. This study was aimed to evaluate the triage performance of combined HPV DNA testing and genotyping. Cervical samples from women with minor cytological abnormalities, who underwent colposcopy at Chiang Mai University Hospital in northern Thailand between October 2010 and February 2014, were tested for HPV DNA using Hybrid Capture 2 (HC2). Genotyping was performed using Linear Array assay. Of 223 women with cervical histology confirmation, histologic HSIL+ was detected in 25 women (11.2%). The sensitivity, specificity, positive predictive value, and negative predictive value of 3 triage methods for histologic HSIL+ were; 100%, 47.5%, 19.4%, and 100% by HC2 only; 40.0%, 88.4%, 30.3%, and 92.1% by combined HC2 and genotypes HPV16/18; and 96.0%, 75.8%, 33.3%, and 99.3% by combined HC2 and genotypes HPV16/18/52/58. Triage using combined HC2 and genotypes HPV16/18/52/58 showed significantly greater area under the receiver operating curve than the other 2 methods ( P < 0.001). Combined HPV DNA testing and genotyping for HPV16/18/52/58 is useful for triaging women with minor cervical cytological abnormalities in northern Thailand. J. Med. Virol. 88:135-143, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Persistent infection with human papillomavirus, especially high risk ones, is a necessary cause of cervical cancer. This study aimed to investigate the distribution of HPV genotypes in female outpatients from Qingdao, East China. A total of 4,534 cervical swabs from women visiting this medical institution for gynecologic care were included. HPV genotypes were examined by a PCR-based hybridization gene chip assay and liquid-based cytology analysis was used to evaluate cervical cytology. The overall HPV prevalence in this study was 32.2% (1,459/4,534). A total of 23 HPV genotypes were identified and the five most prevalent ones were HPV16 (16.1%), HPV52 (8.9%), HPV58 (7.9%), HPV6 (7.0%), and HPV53 (6.5%). Age-specific prevalence of HPV exhibited one peak at the youngest age group and the HPV positive rate decreased gradually with age growth. But high risk HPV infections were more prevalent among aged women. Besides, association between cervical cytology and HPV infection was also determined, 27.2% (1124/4,126) of women with normal cytology were HPV positive while 82.1% (335/408) of women with abnormal cytology were HPV positive. These findings give new epidemiological data and may provide guidance for the vaccination program in this area. J. Med. Virol. 87:2114-2121, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background In 2006, Australia adopted a revised cervical cytology terminology system, known as the Australian Modified Bethesda System ( AMBS). One substantial change in the AMBS was the introduction of the diagnostic category of atypical endocervical cells ( AEC) of undetermined significance. Aim The aim of this study was to investigate the incidence of histologically confirmed high-grade cervical dysplasia (cervical intra-epithelial neoplasia ( CIN) grades 2 and 3 and adenocarcinoma in situ ( ACIS)), cervical carcinoma and endometrial carcinoma in women presenting with AEC on cervical cytology. Methods A seven-year retrospective study examining clinical outcomes of women with AEC on a screening cervical smear. Cytology and histology results were extracted from the Western Australia Cervical Screening Registry, and time-to-event analysis was used to predict the odds of having or developing in situ and invasive neoplasia. Results AEC was reported in index smears from 0.093% (584/622754) women during the study period. No follow-up was available in 35 AEC cases. Sixty-five of the remaining 549 women (11.8%) had, or developed, high-grade cervical dysplasia within five years of their index AEC diagnosis. Endometrial cancer was diagnosed in 21 women and cervical cancer in four women during the follow-up period. Conclusion Cytologic demonstration of AEC requires careful gynaecologic evaluation, particularly in younger women who may be found to have either high-grade squamous ( CIN) or glandular ( ACIS) lesions, while in older women, the possibility of endometrial neoplasia needs to be considered. [ABSTRACT FROM AUTHOR]

BACKGROUND Testing for the presence of the human papillomavirus (HPV) is widely accepted for triaging Papanicolaou cytology results categorized as atypical squamous cells of undetermined significance (ASC-US). In contrast, HPV testing has limited use in triaging cytological low-grade squamous intraepithelial lesions (LSILs) due to prevalence rates of typically >80%. In the current study, the authors assessed the diagnostic performance of p16/Ki-67 dual-stained cytology in triaging ASC-US and LSIL cases within the prospective, multicentric Primary ASC-US LSIL Marker Study (PALMS). METHODS A total of 575 ASC-US cases and 529 LSIL cases from a cohort of 27,349 women who were prospectively enrolled into the PALMS study in 5 European countries were tested with p16/Ki-67 dual-stained cytology and Hybrid Capture 2 (HC2) HPV testing. Colposcopy-guided biopsy results of cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) were used as clinical endpoints. RESULTS p16/Ki-67 dual-stained cytology demonstrated comparable (ASC-US: 94.4% for dual-stained cytology vs 100% for HC2 testing; P = .317) or lower (LSIL: 85.7% for dual-stained cytology vs 98.4% for HC2 testing; P = .005) sensitivity for CIN2+, but higher levels of specificity compared with HC2 HPV testing in both ASC-US (78.7% vs 60.4%; P<.001) and LSIL (53.3% vs 15.6%; P<.001) cases. Positive predictive values for CIN2+ were substantially higher for dual-stained cytology versus HC2 HPV testing, especially in LSIL, and in ASC-US cases for women aged <30 years. CONCLUSIONS The clinical usefulness and efficiency of triaging women with ASC-US or LSIL Papanicolaou cytology results by p16/Ki-67 dual-stained cytology testing has been confirmed in this prospective, pan-European study. The high positive predictive value of dual-stained cytology for the presence of high-grade CIN may help to reduce the number of unnecessary colposcopy referrals. Cancer (Cancer Cytopathol) 2015;123:373-81. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

Primary human papillomavirus (HPV)-based screening results in a 2-5% lower specificity for cervical intraepithelial neoplasia Grade 2 or worse (CIN2+) compared to Pap cytology. To identify HPV-positive women with CIN2+, we retrospectively evaluated the cross-sectional and longitudinal performance of p16/Ki-67 dual-stained cytology in HPV-positive women with normal cytology participating in population-based cervical screening. Conventional Pap cytology specimens of 847 of these women derived from the VUSA-Screen study were dual-stained for p16/Ki-67. Cross-sectional clinical performance in detecting CIN3 or worse (CIN3+), and CIN2+ was compared to that of baseline HPV genotyping. Moreover, 5-year cumulative incidence risks (CIR) for CIN3+ (CIN2+) were determined. The sensitivity of p16/Ki-67 dual-stained cytology for CIN3+ (CIN2+) was 73.3% (68.8%) with a specificity of 70.0% (72.8%). HPV16/18 genotyping showed a sensitivity for CIN3+ (CIN2+) of 46.7% (43.8%), with a specificity of 78.3% (79.4%). The 5-year CIR for CIN3+ in HPV-positive women with normal cytology was 6.9%. Testing these women with p16/Ki-67 dual-stained cytology resulted in a significantly lower CIN3+ 5-year CIR of 3.3% ( p = 0.017) in case of a negative test result. A negative HPV16/18 genotyping test result also led to a lower 5-year CIN3+ CIR of 3.6%. p16/Ki-67 dual-stained cytology detects more than 70% of underlying CIN3+ lesions in HPV-positive women with normal cytology at baseline and is therefore suitable for triaging these women to colposcopy. Furthermore, the CIN3+ 5-year CIR of 3.3% after a negative dual-stain result is significantly lower compared to the 5-year CIR of 6.9% in women without p16/Ki-67 dual-stained cytology triage. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association of human papillomavirus (HPV) 16 and non-16 genotype, p16/Ki-67 dual staining and koilocytosis and their role in the prediction of the clinical outcome of low-grade squamous intraepithelial lesion (LSIL) cytology. Methods: One hundred and fifty-five patients with LSIL were followed up and recorded as progression, persistence or regression. HPV genotyping was performed for high-risk HPV (hrHPV) DNA-positive cases. Koilocytosis was reviewed and p16/Ki-67 dual staining was performed on reprocessed conventional cytology slides. Results: HPV16 was the most frequent genotype found in 16.3% of cases. p16/Ki-67 dual staining was positive in 36.1% of all cases. Progression, including concurrent cervical intraepithelial lesion grade 2 or above (CIN2+), was recorded in 13.8% of cases. A statistically significant difference between progressive and non-progressive cases was shown by the following: hrHPV-positive versus hrHPV-negative (P = 0.022), HPV16-positive versus non-16 HPV-positive (P < 0.001) and p16/Ki-67-positive versus p16/Ki-67-negative (P < 0.001) cases. Cases with combined HPV16 and p16/Ki-67 positivity showed the highest progression rate (58.3%). Non-koilocytic HPV16-positive cases showed a 50% progression rate compared with 10.1% for koilocytic non-16 HPVpositive cases (P = 0.010). The sensitivity of p16/Ki-67 dual staining for the detection of CIN2+ lesions was 80%, comparable with hrHPV (85%). The specificity of p16/Ki-67 dual staining was 71% and of hrHPV 42%. The highest specificity was found for HPV16 genotype presence (91%), but with low sensitivity (50%). Conclusion: HPV genotyping, p16/Ki-67 dual staining and koilocytic morphology can be useful in the prediction of clinical outcome in women initially diagnosed with LSIL cytology. [ABSTRACT FROM AUTHOR]

Objectives To discuss the role and training of cytotechnologists ( CTs) in Europe, to identify areas of good practice and to provide an informed opinion to those providing guidelines for training and practice in Europe. Methods All members of the Editorial Advisory Board of Cytopathology were invited to take part in a 'discussion forum' for which six topics were circulated in advance concerning the roles of CTs with regard to: (1) pre-screening slides; (2) 'signing out' reports; (3) carrying out ancillary techniques; (4) supervising laboratory staff; (5) taking part in rapid on-site evaluation ( ROSE) of fine needle aspirates ( FNAs); and (6) whether CTs were trained specifically in cytopathology or in general histopathology. Notes of the meeting were circulated by email and a final report was agreed by 22 participants from 17 predominantly European countries. Results Training for CTs throughout Europe was variable, especially for non-gynaecological cytology, which was inconsistent with the range of activities required. The participants recommended graduate entry, preliminary training in general laboratory technology, and subsequent training to take account of the probability and, in some centres, the reality of primary cervical cancer screening changing from cytology to human papillomavirus ( HPV) testing. They further recommended that CTs should perform HPV tests and take part in ROSE for FNAs, and they supported the European Federation of Cytology Societies developing guidelines for training and practice. Conclusion With CT training added to a university-based education in laboratory or biomedical science, a career in cytotechnology should be an attractive option involving a diverse range of laboratory and clinically based activities. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To determine the prevalence of abnormal cervical smears and high-grade lesions among HIV-positive and HIV-negative women, and to assess the relationship between severity of disease and CD4 count. Methods: In a prospective cross-sectional comparative study, 250 HIV-positive and 250 HIV-negative women attending the University of Port Harcourt Teaching Hospital, Port Harcourt, Nigeria, were enrolled between January and March 2012. Cervical smear samples were collected from participants, examined, and reported via the Bethesda system. Data management and analysis was done with SPSS. Differences between the 2 study groups were determined by χ2 test and Student t test. Results: The prevalence of abnormal cervical smears was significantly higher among HIV-positive women (34.4%) than among HIV-negative women (20.2%) (P <0.01). The proportion of high-grade lesions was significantly higher among HIV-positive women (23.5%) than among HIV-negative women (8.2%) (P =0.025). HIV-positive women with a CD4 count below 500 cells/mm3 had significantly more abnormal cervical smears (28.3%) compared with those with a CD4 count of 500 cells/mm3 or more (6.1%) (P =0.04). Conclusion: HIV-positive women were found to be at significantly greater risk of developing abnormal cervical cytology and high-grade lesions compared with HIV-negative women. [Copyright &y& Elsevier]

The aim of this study was to investigate the relationship between viral load in single human papillomavirus (HPV) 16 or 52 persistent infection and the progression of later cytopathological findings in the uterine cervix. Cervical cytology and HPV genotyping tests were repeated within 3-6 months in 305 women with oncogenic HPV. Twenty-four cases of single HPV 52 persistent infection and 24 cases of single HPV 16 persistent infection were identified. Cases with later cytopathological findings showing progression were defined as the progression group, while those with no change or regression were the non-progression group. Relative HPV DNA loads were determined by quantitative real-time polymerase chain reaction and expressed relative to human albumin (ALB) DNA. Differences between the two groups were evaluated. The median relative HPV 52 DNA load was 2.211 in the progression group and 0.022 in the non-progression group (Mann-Whitney U-test, P = 0.003). The median relative HPV 16 DNA load was 4.206 in the progression group and 0.103 in the nonprogression group (P = 0.001). HPV 52 and 16 DNA loads assessed by quantitative real-time methods may be useful short-term markers for identifying women at high risk for progression of cervical cytological pathology. [ABSTRACT FROM AUTHOR]

Objective Cytology laboratories routinely treat cervical liquid-based cytology ( LBC) specimens that are heavily contaminated with blood with glacial acetic acid ( GAA) in order to lyse red blood cells and facilitate assessment. However, the impact on downstream human papillomavirus ( HPV) detection is not well understood. This study examines the effect of GAA pre-treatment of ThinPrep® Preservcyt® specimens on the molecular detection of HPV. Methods A panel of 150 routinely collected cervical LBC specimens was tested with two commercial HPV tests, the Abbott RealTime High Risk HPV test ( rt HPV) and the Qiagen Hybrid Capture 2 High Risk HPV DNA test ( HC2), as aliquots before and after GAA treatment. Statistical analysis was performed using McNemars test and Bland and Altman plots. Results Agreement between the results of the rt HPV test on GAA-untreated and GAA-treated specimens was 95.7%, with no evidence of a significant difference in the distribution of the discrepant results ( P = 0.414). HC2 test agreement on GAA-untreated and GAA-treated specimens was 91% at a cut-off of 1 relative light unit index ( RLUI) and 92% at a cut-off of 2 RLUI. There was no evidence of a difference in the distribution of discordant results at a cut-off of 1 ( P = 0.405) and 2 RLUI ( P = 0.564). Conclusions GAA pre-treatment of cervical ThinPrep Preservcyt LBC specimens had little effect on the two commercial HPV tests used in this study. The impact of GAA treatment on HPV testing should, however, be validated for all HPV tests and all LBC collection media used in each particular diagnostic setting. [ABSTRACT FROM AUTHOR]

Objective To investigate the sampling performance of individual cervical cytology practitioners using the transformation zone sampling rate ( TZSR) as a performance indicator and to assess the impact of dedicated on site training for those identified with a low TZSR. Methods The TZSR was calculated for all practitioners submitting ThinPrep® cervical cytology specimens to the Conquest laboratory between January 2010 and November 2011. After excluding those with less than 30 qualifying samples the 10th percentile of the TZSR was calculated. Practitioners with a TZSR below the 10th percentile were visited by a specialist cervical cytology screening facilitator after which the TZSR of these practitioners was closely monitored. Results After exclusions there were 175 practitioners who had collected 24 358 qualifying liquid-based cytology ( LBC) samples. The average TZSR was 70% (range 12-96%). The 10th percentile was 44%; 18 scored below the 10th percentile. Failure to apply sufficient pressure when sampling was identified as the most common reason for a low TZSR. In some cases there was suspicion that the cervix was not always adequately visualized. Continuous monitoring after assessment identified improvement in the TZSRs of 13/18 practitioners. Conclusions Identification of practitioners with low TZSRs compared with their peers allows these individuals to be selected for personalized observation and training by a specialist in cervical cytology which can lead to an improvement in TZSR. As previous studies show a significant correlation between the TZSR and the detection rate of cytological abnormality it is useful to investigate low TZSRs. [ABSTRACT FROM AUTHOR]

A. Umana, H. Dunsmore, A. Herbert, A. Jokhan and A. Kubba Are significant numbers of abnormal cells lost on the discarded ThinPrep® broom when used for cervical cytology? Background: In view of a study with SurePath® showing that cells were lost on the broom if it was discarded, we decided to investigate whether cells were lost on the ThinPrep® (TP) broom, which is discarded according to the manufacturer's protocol. Aim: To determine whether significant amounts of cellular material are lost on the discarded TP broom, and whether the loss is operator dependent. Methods: Three hundred and six women attending the Guy's Hospital Colposcopy Unit gave their consent for TP liquid-based cytology samples to be taken and the broom immersed in a second vial instead of being discarded. The cellularity of the first and second vials was compared by counting cells in 10 ×40 high-power fields (HPFs). The significance of cell loss was ascertained by correlating the likelihood of abnormal cells and transformation zone (TZ) material being present with the degree of cellularity of the two vials. Results: More than 10 cells per HPF were seen in 3.2%, 19.4% and 35.8% of slides from the second vial taken by three experienced colposcopists, which was significantly different between them ( P < 0.001); cellularity of the first vial was not significantly different between colposcopists but the one with highest cellularity in the first vial discarded most in the second. Abnormal cells were more likely to be seen in slides with more than 10 cells per HPF ( P < 0.001) and with evidence of TZ sampling ( P < 0.001), but there was no preferential loss of TZ material in the second vial. Of 126 slides with abnormal cells on the slides from the second vial, 113 (89.7%) were also present on the significantly more cellular first vial ( P < 0.001). Conclusion: Abnormal cells were potentially lost on the broom, but were usually represented in the first vial. The likelihood of abnormal cells being discarded was operator dependent in this small study, but this did not affect the quality of the initial preparation. The likelihood of abnormal cells being seen on TP slides was dependent on their cellularity, which provided our laboratory with a criterion for the assessment of sample adequacy. [ABSTRACT FROM AUTHOR]

BACKGROUND Cytology is an excellent method with which to diagnose preinvasive lesions of the uterine cervix, but it suffers from limited specificity for clinically significant lesions. Supplementary methods might predict the natural course of the detected lesions. The objective of the current study was to test whether a multicolor fluorescence in situ hybridization (FISH) assay might help to stratify abnormal results of Papanicolaou tests. METHODS A total of 219 liquid-based cytology specimens of low-grade squamous intraepithelial lesions (LSIL), 49 atypical squamous cells of undetermined significance (ASCUS) specimens, 52 high-grade squamous intraepithelial lesion (HSIL) specimens, and 50 normal samples were assessed by FISH with probes for the human papillomavirus (HPV), MYC, and telomerase RNA component ( TERC). Subtyping of HPV by polymerase chain reaction (PCR) was performed in a subset of cases (n=206). RESULTS There was a significant correlation found between HPV detection by FISH and PCR ( P<.0001). In patients with LSILs, the presence of HPV detected by FISH was significantly associated with disease progression ( P<.0001). An increased MYC and/or TERC gene copy number (>2 signals in>10% of cells) prevailed in 43% of ASCUS specimens and was more frequent in HSIL (85%) than in LSIL (33%) (HSIL vs LSIL: P<.0001). Increased TERC gene copy number was significantly correlated with progression of LSIL ( P<.01; odds ratio, 7.44; area under the receiver operating characteristic curve, 0.73; positive predictive value, 0.30; negative predictive value, 0.94) CONCLUSIONS The detection of HPV by FISH analysis is feasible in liquid-based cytology and is significantly correlated with HPV analysis by PCR. The analysis of TERC gene copy number may be useful for risk stratification in patients with LSIL. Cancer (Cancer Cytopathol) 2013;121:423-31. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To document Georgian physician’s knowledge, attitudes, and practices concerning HPV, Pap smear testing, and HPV vaccination, and to assess whether physician practice might change with additional education and training. Methods: A cross-sectional study was conducted using a self-administered written survey of 288 physicians practicing in 7 healthcare institutions in Tbilisi, Rustavi, and Batumi, Georgia. Data were collected on demographics, conduct of and perceived barriers to Pap smear testing, knowledge about HPV and HPV vaccination, and willingness to receive education and training about HPV and cervical cancer. Univariate counts and proportions were calculated. Pap smear testing and barriers were compared across demographics using bivariate and Poisson regression with robust error variance methods. Results: Overall, 54% of physicians never performed Pap smears; most reported testing was not their responsibility. Most (88%) obstetricians/gynecologists performed Pap smears. Younger physicians were more likely to perform Pap smears. Approximately 48% of physicians actively offered the HPV vaccine. Most physicians were receptive to increased education and training about HPV and cervical cancer. Conclusion: Age-related differences in the conduct of and attitudes toward Pap smear testing exist among Georgian physicians. There is an opportunity to increase Pap smear testing and provide evidence-based HPV vaccine counseling in Georgia. [Copyright &y& Elsevier]