Atypical Squamous Cells Of Undetermined Significance Cases Research Articles

Assessment of Cervicovaginal Smear and HPV DNA Co-Test for Cervical Cancer Screening: Implications for Diagnosis and Follow-Up Strategies.

Cervical cancer is a major cause of cancer-related mortality, necessitating effective screening and diagnostic methods. This study aimed to assess the performance of cervicovaginal smear (CVS) and human papillomavirus (HPV)-DNA co-test. The pathology results of 225 female patients who underwent HPV-DNA testing with CVS between 2014 and 2022 and were subsequently diagnosed by colposcopic cervical biopsy or second CVS were retrospectively analyzed. CVS samples showed atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), and cervical cancer. Concordance between the first and second diagnoses demonstrated moderate agreement for LSIL. ASCUS cases exhibited a significant correlation with HPV-DNA positivity and higher-grade cervical lesions. In biopsy, sensitivity and specificity for CIN1/LSIL were 87.5% and 53.3, respectively, while for CIN2-3/HSIL, they were 83.87% and 58.49%. HPV testing showed significant correlation with histopathologic results. In women over 40 years, more intraepithelial lesions were diagnosed compared to younger women (p < 0.005). The conventional smear technique proved reliable in detecting high-grade lesions. Despite the limitations of our study, our results emphasize the value of HPV-DNA testing to avoid unnecessary interventions and to establish appropriate follow-up strategies.

Validation of HPV triage in cytology-based cervical cancer screening for ASC-US cases using Japanese data.

In Japan, cervical cancer screening consists of a cytology examination performed once every 2 years. We verified whether the risk of cervical intraepithelial neoplasia (CIN) 3 disease or higher (CIN3+) was equivalent to that of cytology negative cases (negative for intraepithelial lesion or malignancy [NILM]) for patients with a cytological diagnosis of "atypical squamous cells of undetermined significance (ASC-US)" who tested negative for human papillomavirus (HPV). Data from a total of 22,925 cases who had undergone cervical cancer screening at least twice or who had completed follow-up examinations after cervical screening at a single facility between April 2013 and April 2018 were analyzed. The cumulative incidence of CIN3+ was calculated for each category of initial cytology finding and HPV result (NILM, > ASC-US, ASC-US/HPV (unknown), ASC-US/HPV+, and ASC-US/HPV-). The statistical analysis was conducted using the Cox proportional hazards model. The hazard ratio for the cumulative incidence of CIN3+ in 2 years relative to that for NILM cases was 2.7 (95% confidence interval=1.0-7.8) for > ASC-US cases, 0.5 (0.1-1.7) for ASC-US/HPV (unknown), 0.8 (0.3-2.4) for ASC-US/HPV+ cases, and 0.3 (0.1-1.0) for ASC-US/HPV- cases. Because the cumulative incidence of CIN3+ at 2 years for the ASC-US/HPV- cases was sufficiently low, compared with that of the NILM cases, we considered it reasonable and safe to perform HPV triage for ASC-US cases and to allow HPV-negative cases to return for their next screening in 2 years, which is the same follow-up schedule as that for NILM cases.

Abstract 39: Human Papillomavirus (HPV) DNA Testing Based Cervical Cancer Screening and Triage with CINtec PLUS Cytology Test in HPV Positive Women in Bogalay Township, Ayeyarwady Region, Myanmar

Abstract Purpose: This study aimed to conduct Human Papillomavirus (HPV) DNA testing based cervical cancer screening among married women in Bogalay Township, Ayeyarwady Region, Myanmar and to triage with CINtec PLUS Cytology test among women who have HPV infection. Methods: It was a prospective cross-sectional descriptive study. Total of asymptomatic 677 married women (median age-40-years;range 30-55) residing in Bogalay Township, Ayeyarwady Region, Myanmar were screened in 2020. HPV-DNA testing was performed using cobas HPV-DNA-test which detects 14-high-risk-HPV genotypes -16,-18,-31,-33,-35,-39,-45,-51,-52,-56,-58,-59,-66 and-68. Positive HPV cases were followed by liquid-based- cytology (LBC) and CINtec PLUS Cytology i.e, dual-immuno-biomarker technology to simultaneously detect p-16 and Ki-67 to provide a strong indicator of the presence of transforming HPV infections. Results: HPV was identified in 4.6% (31/677) of screened women in Bogalay Township, Ayeyarwady Region, Myanmar. Among HPV-positive-cases, HPV-16 was 22.6 % (7/31), HPV-18 was 6.5% (2/31) and other-HR-HPV-genotypes (HPV-31,-33,-35,-39,-51,-52,-56,-58,-59,-66and-68) were 70.9% (22/31). In cytological-diagnosis of HPV positive women, 87.1% had cervical cytological abnormalities comprising; 16.1% had high grade squamous intraepithelial lesion (HSIL), 48.4% had low grade squamous intraepithelial lesion (LSIL) and 22.6% had atypical squamous cells of undetermined significance (ASCUS). Only 12.9% were negative for intraepithelial lesion or malignancy (NILM). In CINtec-PLUS-Cytology, all HSIL (100%) cases, 66.7% of LSIL, 14.3% of ASCUS were positive with both p-16 and Ki-67 dual-immuno-biomarker but negative in NILM cases. Conclusion: This study highlighted that using HPV-DNA test in cervical cancer screening, the highest risk women can be determined. In triage with CINtec-PLUS-Cytology in HPV positive women, women who were more significantly at risk for cervical pre-cancer and cancer as well as women that require referral to colposcopy were identified. In LSIL and ASCUS cases, CINtec-PLUS-Cytology may reduce the number of women that require referral to colposcopy. This study pointed out CINtec-PLUS-Cytology was very useful to confirm the high-grade cervical lesions. Citation Format: Mu Mu Shwe, Khin Kay Thwe, Su Su Hlaing, Lynn Pa Pa Aye, Kham Mo Aung, Nu Lwin, Win Maw Tun, Zaw Than Htun. Human Papillomavirus (HPV) DNA Testing Based Cervical Cancer Screening and Triage with CINtec PLUS Cytology Test in HPV Positive Women in Bogalay Township, Ayeyarwady Region, Myanmar [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 39.

Anal cytology and high-risk human papilloma virus testing in atypical squamous categories: Value of concurrent testing in management of high-risk population.

Anal squamous cell carcinoma is relatively rare, but its incidence and mortality have been increasing worldwide. While anal cytology is a sensitive cancer screening modality, its specificity is low, and data for concurrent high-risk human papilloma virus (HR-HPV) testing are limited. At our institution, anal cancer screening consists of combined anal cytology and high-risk human papilloma virus (HR-HPV) testing on all specimens. The aims of the study were to correlate results of atypical cytological diagnoses [atypical squamous cells of undetermined significance (ASCUS) and atypical squamous cells cannot exclude high grade squamous intraepithelial lesion (ASC-H)] with HR-HPV testing and determine if co-testing may potentially influence management. A retrospective search over 24-months was performed for anal cytology specimens with diagnoses of ASCUS and ASC-H. Corresponding HR-HPV (HPV 16/18 and Other-31/33/35/39/45/51/52/56/58/59/66/68) results were retrieved, and concordance/discordance was recorded. Cytology results were correlated with anal biopsy diagnoses, when available. A total of 139 patients, including 127 with ASCUS and 12 with ASC-H, were identified. Of the ASCUS cases, 90/127 (70.9%) had HR-HPV, and a squamous intraepithelial lesion (SIL) was evident in 20/39 (51.2%) of biopsies. All 12/12 (100%) ASC-H were associated with HR-HPV and 3/6 (50%) biopsies had a SIL. Our study supports use of concurrent cytology and HR-HPV for anal cancer screening cytology. Co-testing improves specificity of atypical cytology diagnoses and can identify patients requiring further intervention.

Interpreting a Diagnosis of Atypical Squamous Cells of Undetermined Significance in Cervical Cytology and its Association with Human Papillomavirus: A retrospective analysis of 180 cases in Kuwait.

ObjectivesAtypical squamous cells of undetermined significance (ASC-US) represent a diagnostic challenge during cervical cytology. This study aimed to review and identify high-risk human papillomavirus (HR-HPV) genotypes among previously diagnosed ASC-US cases in Kuwait.MethodsThis retrospective study analysed 180 cases diagnosed as ASC-US between June 2017 and May 2018 at the Mubarak Al-Kabeer Hospital, Kuwait. Cervical specimens were assayed to determine the presence of HR-HPV DNA; subsequently, positive cases underwent genotyping and were categorised into three groups (HPV 16, HPV 18/45 and other HR-HPV types).ResultsIn total, ASC-US was confirmed in only 105 cases (58.3%), with the remaining cases reclassified as negative for intraepithelial lesions or malignancy (NILM; 32.2%) and epithelial cell abnormalities (ECA; 9.4%). Of these, HR-HPV DNA was present in 20 ASC-US (19%), one NILM (1.7%) and six ECA (35.3%) cases. There were 62 Kuwaiti and 43 non-Kuwaiti women with confirmed ASC-US; of these, three (4.8%), six (9.7%) and four (6.5%) Kuwaitis and one (2.3%), one (2.3%) and five (11.6%) non-Kuwaitis had HPV 16, both HPV 16 and 18/45 and other HR-HPV genotypes, respectively. Of those with HR-HPV DNA, the NILM case had the HPV 18/45 genotype, while the six ECA cases had the HPV 16 (n = 1), both HPV 16 and 18/45 (n = 1) and other HR-HPV (n = 4) genotypes.ConclusionOverall, HR-HPV DNA was present in 19% of ASC-US cases compared to 1.7% of NILM cases initially misdiagnosed as ASC-US. Re-review of cervical cytology diagnoses may reduce unnecessary costs associated with HR-HPV genotyping.

Correlation of High-Risk HPV Genotypes with Pap Test Findings: A Retrospective Study in Eastern Province, Saudi Arabia

Introduction: High-risk human papillomavirus (HR HPV) is found to be responsible for 4.5% of cancer in general, primarily cervical cancer. We aim here to highlight the prevalence and genotypes of HR HPV and correlate its association with Pap tests’ results, which are still not well known in the Eastern Province of Saudi Arabia. Methods: Over 7 years (2013–2019), the results of 164 Saudi women coinvestigated for HR HPV along with Pap tests were collected from the archive of King Fahd University Hospital. Only women who had atypical squamous cells of undetermined significance (ASCUS) on the Pap test and those at elevated risk of infection were cotested for HR HPV; otherwise, the Pap test was the only screening modality for cervical cancer. Data were organized and statistically analyzed using IBM SPSS v26. Results: Out of 164 Saudi women, 14.5% (n = 24/164) showed positive results for HR HPV (8 patients had HPV16 and 2 had both HPV16 and HPV18/45, while the remaining 14 had other HR HPV); among them, 41.5% (n = 10/24) had an abnormal Pap test (5 ASCUS and 5 LSIL), while 58.5% (n = 14/24) had a negative Pap test. On the other hand, 21% (n = 35/164) of patients, in the study, had an abnormal Pap test (24 ASCUS, 8 low-grade squamous intraepithelial lesion [LSIL], and 3 atypical glandular cell [AGC]). In 80% (n = 19/24) of ASCUS cases, HR HPV was not detected; however, 20% (n = 5/24) were positive for other HR HPV. Concerning LSIL cases, 62.5% (n = 5/8) were positive for HR HPV (1 case showed HPV16 and HPV18/45, 2 cases showed HPV16, and 2 cases showed other HR HPV), while in the remaining 37.5% (n = 3/8) LSIL cases, HR HPV was negative; similarly, all AGC cases were negative for HR HPV. Statistical analysis showed a significant correlation between HPV status and Pap test findings (p value <0.001). Discussion/Conclusion: HR HPV frequency and genotype distribution, in this study, might reflect a different regional infection pattern. The high association of HR HPV with negative cytology emphasizes the need to add the HR HPV test to screening modalities of cervix cancer.

Atypical squamous cells of undetermined significance cervical cytology in the Chinese population: Age-stratified reporting rates, high-risk HPV testing, and immediate histologic correlation results.

The US American Society of Colposcopy and Cervical Pathology guidelines for cervical cancer screening have been largely adopted worldwide. Pooled high-risk human papillomavirus (hrHPV) testing has been routinely used to risk-stratify women who have atypical squamous cells of undetermined significance (ASC-US) cytology. However, it has been reported that there are distinguished differences in the distribution of hrHPV genotypes between the Chinese and American populations. The objective of this study was to analyze the age-stratified reporting rates, hrHPV-positive rates, and genotyping by different cytology preparation methods and hrHPV testing assays, along with the immediate histopathologic correlation of ASC-US cytology, in the Chinese population. The ASC-US reporting rate of 1,597,136 Papanicolaou (Pap) tests was 4.2%, and the overall hrHPV-positive rate was 48.7% in the ASC-US cases. In total, 25,338 women with ASC-US Pap tests had immediate histologic follow-up, and the detection rate for cervical intraepithelial neoplasia 2 and higher lesions (CIN2+) was 7.1%, including 0.6% carcinomas. Among the women who underwent hrHPV testing, CIN2+ lesions were identified in 657 of 6154 (10.7%) who had hrHPV-positive results and in only 1.5% those who had hrHPV-negative results. Further genotyping analysis revealed that HPV types 16 and/or 18 were commonly identified genotypes among the Chinese women who had ASC-US cytology. This large-scale study demonstrated that the hrHPV-positive rate, the CIN2+ detection rate, and the distribution of hrHPV genotypes in Chinese women with ASC-US cytology were essentially consistent with those from the American population, further supporting that the current and newly released 2019 American Society of Colposcopy and Cervical Pathology guidelines should be applicable to the Chinese population.

A study of the relationship between nuclear contour thickening, nuclear enlargement and human papillomavirus infection in squamous cells.

To investigate the relationship between the morphological features of nuclear enlarged cells and human papillomavirus (HPV) infection in negative for intraepithelial lesion or malignancy (NILM) and atypical squamous cells of undetermined significance (ASC-US). In total, 128 Papanicolaou specimens comprising 41 ASC-US cases and 87 NILM cases were examined. Cell morphological analysis was performed using both area ratio (nuclear area in cells with nuclear enlargement/nuclear area in normal intermediate cells) and nuclear contour thickening. High-risk HPV was detected using the Uniplex E6/E7 polymerase chain reaction assay and logistic regression analyses of factors related to high-risk HPV infection were performed. Nuclear contour thickening was present in 57.7% (64/111 cells) of high-risk HPV positive cases and 21.8% (69/317 cells) of high-risk HPV negative cases. There was a statistically significant association (P=0.01) between high-risk HPV infection and nuclear contour thickening. Nuclear contour thickening was approximately one-third higher in NILM cases than in ASC-US cases (odds ratio, 0.371; 95% confidence interval, 0.208-0.662) and three times higher in high-risk HPV-positive cases than in high-risk HPV-negative cases (odds ratio, 2.831; 95% confidence interval, 1.591-5.039). Our results suggest that nuclear contour thickening in nuclear enlarged cells in NILM and ASC-US cases may be a cellular finding associated with HPV infection.

Atypical Squamous Cells of Undetermined Significance Cervical Cytology Report Rate and Histologic Follow-up Findings From the Largest College of American Pathologists-Certified Laboratory in China.

Reports for atypical squamous cells of undetermined significance (ASC-US) and histologic findings are rare in China. To analyze the correlation findings of ASC-US cytology with high-risk human papillomavirus (hrHPV) test and histopathologic follow-ups. ASC-US cases with hrHPV test and histologic follow-ups between 2011 and 2015 were analyzed at a College of American Pathologists-certified laboratory. A total of 2 206 588 Papanicolaou (Pap) tests were performed, including 1 513 265 liquid-based cytology preparations (68.58%), and 693 323 conventional Pap tests (31.42%). The overall ASC-US reporting rate was 3.77% (83 199 of 2 206 588), with the highest in women aged 40 to 49 years. Of 18 574 women with ASC-US Pap and HPV testing, the hrHPV positivity rate was 34.98% (6498 of 18 574) with the highest in women younger than 30 years. A total of 6012 women with ASC-US Pap test findings had histologic follow-ups within 6 months; the overall cervical intraepithelial neoplasia 2 and above (CIN2+) detection rate was 7.87% (473 of 6012). One thousand nine hundred nine women with ASC-US Pap and HPV testing had histologic results. CIN2+ lesion was found in 13.98% (124 of 887) of women with ASC-US Pap/HPV-positive test results, significantly higher than 2.84% (29 of 1022) for women with ASC-US Pap/HPV-negative test results. Cervical squamous cell carcinoma was found in 3.95% (35 of 887) of women with ASC-US/HPV-positive test results. This is one of the largest studies to investigate HPV and histologic follow-up findings in women with ASC-US in China. The ASC-US reporting rate, HPV positivity rate, and CIN2+ detection rate were all within the currently recognized benchmark ranges. These findings may contribute to establishing a baseline for better understanding of the status of cervical screening in China.

ASCUS (Atypical Squamous Cells of Undetermined Significance) in the Cervical Smears of Women from Rural Population of Lucknow West.

Though Atypical squamous cells of undetermined significance (ASCUS) are not always precursors of cervical pre-malignancy but they need timely diagnosis and careful periodical follow-up. The present study was carried out to investigate the incidence of ASCUS and SIL (squamous intraepithelial lesion of cervix) in women under rural setting. Cervical cancer screening is in progress in rural population of West Lucknow, India, since May 2013 under auspices of Era's Lucknow Medical College and Hospital, Lucknow, and a total of 2478 women have been cytologically examined till October 2017. The incidence of ASCUS was found to be 8.8%, which was approximately less than half of the squamous intraepithelial lesions of cervix (SIL) rate (17.9%). The ASCUS rate was higher in the symptomatic women (9.4%) than (7.4%) seen in women without symptoms. The ASCUS incidence was higher in younger sexually active group up to 40years after which it declined. The ASCUS rate was higher in all parity groups and was commonly associated with pain in lower abdomen and vaginal discharge. The ASCUS rate was higher with erosion cervix, while the commonly associated sexually transmitted diseases (STD) were found to be Candida albicans (2.4%). Follow-up after 18-24months was available in 40 cases of ASCUS, and progression to low-grade SIL (LSIL) was seen in 7 (17.5%) and to high-grade SIL (HSIL) in one case (2.5%). The findings suggest that the ASCUS are not always precursors of SIL, but they need periodical follow-up after every 6months. This will be ideal management of ASCUS under low-resource settings.

Management of Atypical Squamous Cell Cases: A Prospective Study of Women seen at a Private Health Service in Northeastern Brazil.

To assess the management chosen by gynecologists after atypical squamous cells (ASCs) cytology results, and to evaluate the outcomes of these cases in Brazilian women. A prospective observational study evaluated the initial management offered by the gynecologist in the case of 2,458 ASCs cytology results collected between January of 2010 and July of 2016. The outcomes of the cytology, high-risk human papilloma virus (HR-HPV) test and histology were compared in two subgroups: atypical squamous cells of undetermined significance (ASC-US) and atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (ASC-H). In many cases of ASC-US (36.97%) and ASC-H (40.50%), no clinical actions were taken. Cytology was the most frequent follow-up chosen, including for cases of ASC-H, which goes against the conduct recommended in the national guideline. In women over 30 years of age, the period of time elapsed between an ASC-US result and a new cytology was in 13.03 months, in disagreement with the national guideline recommendations (p < 0.0001). Negative for intraepithelial lesions or malignancy (NILM) cytologic (p = 0.0026) and histologic (p = 0.0017) results in the follow-up were associated with prior ASC-US, while negative results for ASC-H were cytologically (p < 0.0001) and histologically associated with high-grade squamous intraepithelial lesion (HSIL) (p < 0.0001). Two invasive cervical carcinomas (ICCs) were found in the follow-up for ASC-H, and there was a statistically significant association (p = 0.0341). A positive HR-HPV test was associated with ASC-H (p = 0.0075). The data suggest that even for a population of Brazilian women assisted at private clinics, the national guidelines recommendations for ASCs results are not followed.

Sorting role of p16(INK4a)/Ki-67 double immunostaining in the cervical cytology specimens of ASCUS and LSIL cases

Objective: To investigate the sorting effect of p16(INK4a)/Ki-67 double immunostaining method in patients with atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) cytology results. Methods: Four-hundred and twenty cases collected during April 2014 to February 2015 of cervical cytology of ASCUS (n=318) and LSIL (n=102) were selected, and residual liquid-based cytology specimens were used for p16(INK4a)/Ki-67 double immunostaining. The sensitivity and specificity of the detection of cervical precancerous lesions and cervical cancer were calculated, and the results were compared with high risk HPV. Taking histological follow-up as the gold standard, the test was considered positive when at least one cell exhibited p16(INK4a)/Ki-67 co-staining, without requirement of adjunct morphologic interpretation of positive cells. Results: Further screening CIN2+ in cytology ASCUS and LSIL group , the sensitivity of p16(INK4a)/Ki-67 double immunostaining was slightly lower than high risk HPV (84.2% vs. 94.7%), while the specificity was higher (84.0% vs. 53.9%). For ASCUS patients, the sensitivity of p16(INK4a)/Ki-67 double immunostaining and high risk HPV was 82.6% and 91.3%, and the specificity was 88.8% and 63.7%, respectively. For LSIL patients, the sensitivity of p16(INK4a)/Ki-67 double immunostaining and high risk HPV was 86.7% and 100.0%, and the specificity was 67.8% and 20.7%, respectively. For patients younger and older than 30 years, specificity of p16(INK4a)/Ki-67 double immunostaining was both higher than that of high risk HPV (80.8% vs. 42.3%; 84.6% vs. 56.9%). Conclusions: p16(INK4a)/Ki-67 double immunostaining can effectively identify the high risk population in ASCUS or LSIL, with higher specificity than high risk HPV test. p16(INK4a)/Ki-67 double immunostaining may benefit patients younger than 30 years of age as a preliminary or potential cytology-combining screening tool.

Cumulative High-Grade Squamous Intraepithelial Lesion Rate and Need for Surgical Intervention of Atypical Squamous Cells of Undetermined Significance Cytology-Diagnosed Patients: A Prospective Study

Objective: Τhe study aimed to study the rate of atypical squamous cells of undetermined significance (ASCUS) that progressed to high-grade squamous intraepithelial lesions (HGSIL), as well as the number of patients who finally necessitated a surgical intervention during follow-up. Methods: A prospective study was conducted on patients admitted for colposcopy during 2007-2012. We exclusively included those who presented with newly ASCUS diagnosis, while patients with a history of cervical intraepithelial neoplasia (CIN) were excluded. Primary end points were the cumulative rate of HGSIL during follow-up and the rate of surgical procedures performed because of such lesions. Results: There were 134 ASCUS cases included. Overall, there were 48 (35.8%) surgical excision procedures performed to treat or eliminate HGSIL during the follow-up period. According to the final histopathology of surgical specimens, the cumulative rate of CIN2 or higher cervical lesions was 28.4% (n = 38). Conclusion: The cumulative rate of CIN2+ during follow-up period was almost 30% for patients with ASCUS, with the necessity for interventional treatment being even higher.

Beneficial Effects of Human Papillomavirus Vaccine for Prevention of Cervical Abnormalities in Miyagi, Japan.

Prevention of cervical cancer has been unsuccessful in Japan because of low rates of cancer screening and vaccination. The Vaccine Adverse Review Committee of the Japanese Government investigated 2,475 adverse events and reported 617 (6.9/100,000) severe cases and 176 (2.0/100,000) cases with chronic pain. The proactive recommendation for human papillomavirus (HPV) vaccination has been suspended since June 2013. In this study, we examined vaccination rate and incidence of abnormal cervical cytology in women aged 20 to 24 years attending cancer screening in Miyagi. Among the 3,272 women who underwent a health check in the fiscal year 2014 (April 2014-March 2015), 332 (10.2%) received a HPV vaccination. The HPV vaccination rates were 42.3%, 10%, 17.5%, 3.8% and 4.0% in women aged 20, 21, 22, 23 and 24 years, respectively. The rates of atypical squamous cells of undetermined significance (ASC-US) or worse were 2.41% (8/332) in women with HPV vaccination and 5.03% (148/2,940) in those without HPV vaccination, indicating a significant decrease in vaccinated women (p = 0.03). ASC-US cases were referred to HPV DNA tests. In addition, the rates of high grade squamous intraepithelial lesion (HSIL) or worse were 0.30% (1/332) in women with HPV vaccination and 0.82% (24/2,940) in those without HPV vaccination, showing the marginal decrease in women who were vaccinated (p = 0.3). Thus, this study indicates that HPV vaccination is associated with a reduction in the incidence of cervical abnormalities, suggesting a need for scientific discussion of reinstatement of proactive recommendation for HPV vaccine in Japan.

Improving the performance of reflex Human Papilloma Virus (HPV) testing in triaging women with atypical squamous cells of undetermined significance (ASCUS): A restrospective study in a tertiary hospital in United Arab Emirates (UAE)

IntroductionCervical cancer is the second commonest cancer in women worldwide. Infection with oncogenic types of human Papillomavirus (HPV) is the most important risk factor for developing cervical cancer. Reflex High risk HPV (HR-HPV) testing is of significant value in the assessment of Papanicolaou (Pap) smear results where ASCUS are identified. ObjectiveTo improve the performance of reflex HR-HPV testing in triage of ASCUS and analyze the factors impacting it. MethodologyIn this study, we generated a database of 9641 women who had cervical smears collected during the study period from the cytopathology record in a large tertiary hospital in UAE. These included 297 smears with ASCUS diagnosis. All cases were retrospectively followed up with a mean duration of 2.44 years. We analyzed data according to the outcome based on several follow-up Pap smear analysis as the reference assessment. ResultsWe detected HR-HPV infection in 17.9% of cases. 9.1% <25, 28.8% 25–34 and 62.1% ≥35 years old. HR-HPV prevalence was higher among premenopausal women (20.7%) compared to postmenopausal women (9.5%) (P-value=0.044). The rate of progression to high grade lesions was also higher (28.7%) in the premenopausal group compared to (12.8%) in the postmenopausal group. Reflex HPV testing had an overall sensitivity of 41.1%, specificity of 88.2%, positive predictive value (PPV) of 62.1%, and negative predictive value (NPV) of 75.9% in detection of cervical lesions. These figures were higher on combining premenopausal status and complaint of abnormal bleeding or discharge/itching (66.7%, 93.3%, 66.8% and 93.3% respectively). ConclusionsThe sensitivity, specificity and NPV of reflex HPV testing in the triage of ASCUS cases can be more accurate in premenopausal women upon adding age group and presenting complaint as a triage item. This improves the performance of reflex HPV testing and the subsequent selection of high risk patients for colposcopy.

Cytology as a screening tool for anal squamous intraepithelial lesion for HIV positive men: 10-year experience in an inner city hospital

Human papillomavirus (HPV) and anal carcinoma are prevalent in high-risk patients including human immunodeficiency virus (HIV)-positive patients. There are currently no clear guidelines for screening, however. We assessed anal cytology specimens and HPV testing at an inner-city hospital by correlating anal cytology with anal biopsy (bx), and evaluated if results differed with traditional proctoscopy (TP) or high-resolution anoscopy (HRA). 209 anal cytology and subsequent biopsies taken during the period 2003-2014 from 152 male patients were reviewed. Demographic data for age, sex, HIV, HPV, cytology, histology, and the method of biopsy were analyzed. All specimens were followed by a biopsy within a period of 6 months. Ninety-seven percent of patients were HIV-positive and 43% had AIDS. Lesions most diagnosed on cytology were low-grade squamous intraepithelial lesion (LSIL) (52%) and atypical squamous cells of undetermined significance (ASC-US) (21.5%). Lesions most diagnosed on bx were anal intraepithelial neoplasia (AIN) grade 2-3 (52%) and AIN grade 1 (37%). Almost all ASC-US cases tested for HPV were positive (97%). There was cytology histology correlation in 48% of LSIL and 83% of high-grade squamous intraepithelial lesions. Anal cytology had 97% sensitivity in detecting AIN and carcinoma and a positive predictive value of 96%. There was no difference in rate of detection of AIN 1and AIN 2-3 on bx using TP versus HRA. Screening in high-risk patients detected almost all high- and low-grade squamous intraepithelial lesions, however, anal cytology alone could not predict the degree of dysplasia. It may be prudent to perform anal bx in all atypical anal cytology. Clear guidelines are needed for screening of a high risk population.

Value of PAX1 Methylation Analysis by MS-HRM in the Triage of Atypical Squamous Cells of Undetermined Significance.

Detection of cervical high grade lesions in patients with atypical squamous cells of undetermined significance (ASCUS) is still a challenge. Our study tested the efficacy of the paired boxed gene 1 (PAX1) methylation analysis by methylation-sensitive high-resolution melting (MS-HRM) in the detection of high grade lesions in ASCUS and compared performance with the hybrid capture 2 (HC2) human papillomavirus (HPV) test. A total of 463 consecutive ASCUS women from primary screening were selected. Their cervical scrapings were collected and assessed by PAX1 methylation analysis (MS-HRM) and high-risk HPV-DNA test (HC2). All patients with ASCUS were admitted to colposcopy and cervical biopsies. The Chi- square test was used to test the differences of PAX1 methylation or HPV infection between groups. The specificity, sensitivity, and accuracy for detecting CIN2 + lesions were: 95.6%, 82.4%, and 94.6%, respectively, for the PAX1 MS-HRM test; and 59.7%, 64.7%, and 60.0% for the HC2 HPV test. The PAX1 methylation analysis by MS-HRM demonstrated a better performance than the high-risk HPV-DNA test for the detection of high grade lesions (CIN2 +) in ASCUS cases. This approach could screen out the majority of low grade cases of ASCUS, and thus reduce the referral rate to colposcopy.

Prospective evaluation of p16/Ki-67 dual-stained cytology for managing women with abnormal Papanicolaou cytology: PALMS study results.

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). 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. 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. 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.

The utility of high-risk HPV testing in the management of women 30 to 64 years of age with low-grade squamous intraepithelial lesions on cervical cytology

The current American Society for Colposcopy and Cervical Pathology guidelines recommend high risk-human papillomavirus testing for patients 30 to 64 years of age with a low-grade squamous intraepithelial lesion on Papanicolaou (Pap) tests. This study presents our experience since the introduction of the new guidelines. From September 1, 2013 through August 31, 2014, 20,014 ThinPrep Pap tests were processed, of which 17,989 (90%) were negative, 863 (4.3%) were atypical squamous cells of undetermined significance (ASCUS), and 540 (2.7%) were low-grade squamous intraepithelial lesions (LSIL). Thirty-eight percent of the negative cases, 87% of the ASCUS cases, and 76% of the LSIL cases were processed for high risk-human papillomavirus genotypes. Of the 1,163 patients with a Pap test diagnosis of ASCUS and LSIL, 656 (56%) underwent colposcopic examination and, of those, 240 (37%) had cervical biopsies performed. In our cohort, 247 (33%) of the 754 ASCUS Pap tests were hr-HPV-positive and 507 (67%) were hr-HPV-negative. Of the 409 LSIL Pap tests, 245 (60%) were hr-HPV-positive and 164 (40%) were hr-HPV-negative. Colposcopy/biopsy follow-up within 3-months of the ThinPrep Pap test showed cervical intraepithelial lesion grade 2/3 lesions in 16% of the hr-HPV-positive ASCUS cases, in 15% of the hr-HPV-positive LSIL cases and in 9% of the hr-HPV-negative LSIL cases. This study supports the current management guidelines of colposcopy for women 30 to 64 years of age with hr-HPV-positive ASCUS and LSIL on Pap tests and repeat Pap test with cotesting for women with hr-HPV-negative LSIL.

Semi-quantitative HPV viral load in patients with ASC-US cytology: viral load correlates strongly with the presence of CIN but only weakly with its severity.

This study was performed to evaluate the prognostic significance of human papillomavirus (HPV) viral load, expressed in relative light units (RLUs), in patients with atypical squamous cells of undetermined significance (ASC-US) cytology. A total of 349 ASC-US cases with HPV infection, detected using Hybrid Capture 2, were diagnosed histologically. A colposcopically directed punch biopsy was performed on acetowhite areas. Endocervical curettage biopsy and random cervical punch biopsy in four quadrants were performed in unsatisfactory colposcopy cases. In negative colposcopy cases, random cervical punch biopsy in four quadrants was performed. Case with no cervical intraepithelial neoplasia (CIN), CIN1 and CIN2+ (CIN2/CIN3) accounted for 162, 135 and 52 cases, respectively. The mean age showed no difference among the three groups (P=0.510). There was a significant correlation between RLU values and the presence of CIN (P<0.001), but less so with its severity: the median RLU values for negative, CIN1 and CIN2+ cases were 42.68, 146.45 and 156.43, respectively, with widely overlapping confidence intervals. The cut-off values of RLU to detect CIN1+ and CIN2+ were 6.73 and 45.64, respectively. The HPV viral load in ASC-US cases showed a significant correlation with the presence of CIN and less so with its severity, and showed large overlap of viral loads between grades of CIN. In ASC-US cases, RLU was not an accurate predictor of immediate high-grade CIN.