Atypical Squamous Cells Of Undetermined Significance Cytology Research Articles

P16/Ki67 dual staining improves the detection specificity of high-grade cervical lesions.

The goal of this study was to analyze the specificity of p16/Ki67 dual staining in the detection of high-grade cervical lesions. A total of 223 patients with an average age of 39 years old were enrolled in this study. All samples were analyzed by p16/Ki67 immunocytochemical dual staining, liquid-based cytology and high-risk human papillomavirus (HR-HPV) test. Diagnosis of each patient was verified by histopathological test. The specificity of p16/Ki67 dual staining was 68.33%, which was significantly higher than that of cytology (38.33%) and HR-HPV test (21.67%) (P < 0.05) for CIN2+ detection. p16/Ki67 dual staining had similar sensitivity with HR-HPV test for CIN2+ detection (90.18% vs 93.87%, P = 0.286). In atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) cases, the specificity of p16/Ki67 dual staining was significantly higher than that of HPV test (66.67% vs 3.70%, P < 0.05) and its sensitivity was similar to that of HPV test for CIN2+ detection. The sensitivity and specificity of dual staining for CIN2+ detection in HR-HPV positive women were 90.85% and 70.21%, respectively, which were higher than those of cytology (83.01% and 42.55%) and HPV16/18 test (70.59% and 44.68%). p16/Ki67 dual staining could improve the specificity of high-grade cervical lesions detection and have similar sensitivity to HPV test for CIN2+ detection. When triaging women with ASC-US or LSIL liquid-based cytology, compared with positive HR-HPV, the specificity of CIN2+ lesion detection was increased by p16/Ki67 dual staining. p16/Ki67 dual staining could reduce colposcopy referrals and avoid excessive diagnosis and treatment.

Liquid-based cytology: do ancillary techniques enhance detection of epithelial abnormalities?

Cervical cancer is the fourth most common cancer in women worldwide with very high incidence in India. Liquid-based cytology (LBC) provides the use of ancillary techniques in addition to a good morphology and detection of cytologic abnormalities. The current study was designed to assess the diagnostics of P16INK4a immunoexpression, p16 promoter hypermethylation, human papilloma virus (HPV), and DNA ploidy in LBC samples with cervical precancer and cancer. A series of LBC samples categorised by Bethesda system including 22 atypical squamous cells of undetermined significance (ASC-US), 21 low-grade squamous intraepithelial lesion (LSIL), 41 high-grade squamous intraepithelial lesion (HSIL), 54 squamous cell carcinoma (SCC), and 26 controls with normal cytology were included. Ancillary techniques evaluated included P16INK4a immunoexpression, p16 promoter methylation DNA ploidy by flow cytometry, and HPV was detected using PGMY09/PGMY11 primers. The test positivity rate of p16 expression in women with ASC-US, LSIL, HSIL, and SCC was 21.1, 39.0, 67.7, and 85.4%. For the p16 methylation the corresponding test positivity rate was 36.4, 76.2, 92.7, and 92.6%. The test positive rate of HPV in women with ASC-US, LSIL, HSIL, and SCC was 45.5, 76.2, 87.8, and 92.6%. Diploid G1 and diploid S values significantly (p < 0.05 or p < 0.01) discriminate LSIL versus HSIL and LSIL versus. SCC. P16 gene promoter methylation and HPV seem more sensitive in detection of ASC-US and LSIL cytology with higher specificity. Diploid G1 and diploid S phase study provides progressive change in parameters with progression from LSIL to HSIL and SCC.

Risks of cervical intraepithelial neoplasia grade 3 or invasive cancers in ASCUS women with different management: a population-based cohort study.

ObjectiveTo investigate the progression risk of atypical squamous cells of undetermined significance (ASCUS) with different clinical managements.MethodsWomen with their first diagnosis of ASCUS cytology were retrieved from the national cervical cancer screening database and linked to the national health insurance research database to identify the management of these women. The incidences of developing cervical intraepithelial neoplasia grade 3 and invasive cervical cancer (CIN3+) were calculated, and the hazard ratios (HRs) were estimated using a Cox proportional hazards model. This study was approved by the Research Ethics Committee of the National Taiwan University Hospital and is registered at ClinicalTrials.gov (Identifier: NCT02063152).ResultsThere were total 69,741 women included. Various management strategies including colposcopy, cervical biopsies and/or endocervical curettage, and cryotherapy, failed to reduce the risk of subsequent CIN3+ compared with repeat cervical smears. Loop electrosurgical excision procedure/conization significantly decreased risk of subsequent CIN3+ lesions (HR=0.22; 95% confidence interval [CI]=0.07–0.68; p=0.010). Women in their 40s–50s had an approximately 30% risk reduction compared to other age groups. Women with a previous screening history >5 years from the present ASCUS diagnosis were at increased risk for CIN3+ (HR=1.24; 95% CI=1.03–1.49; p=0.020).ConclusionIn women of first-time ASCUS cytology, a program of repeat cytology can be an acceptable clinical option in low-resource settings. Caution should be taken especially in women with remote cervical screening history more than 5 years.

Performance of the cobas HPV Test for the Triage of Atypical Squamous Cells of Undetermined Significance Cytology in Cervical Specimens Collected in SurePath.

Determine performance of the cobas human papillomavirus (HPV) test for triage of atypical squamous cells of undetermined significance (ASC-US) in SurePath. Women presenting for routine screening had cervical specimens collected in SurePath and specimen transport medium (STM); those with ASC-US cytology underwent colposcopy. Performance of cobas HPV in SurePath specimens that had undergone a preanalytic procedure to reverse possible cross-linking of HPV DNA was compared with Hybrid Capture 2 (hc2) specimens in STM. Among 856 women, HPV prevalence was 45.8%; HPV 16 and HPV 18 prevalences were lower than expected in the 21- to 29-year-old group in this highly vaccinated population. cobas HPV performance in SurePath was comparable to hc2 in STM. Sensitivity and specificity for detection of cervical intraepithelial neoplasia grade 3 or worse were 87.5% (95% confidence interval [CI], 71.9%-95.2%) and 55.5% (95% CI, 52.1%-58.9%) for cobas and 85.3% (95% CI, 69.9%-93.6%) and 54.7% (95% CI, 51.4%-57.9%) for hc2. Sensitivity was negatively affected by random biopsies performed at colposcopy; comparable sensitivities were achieved in the nonvaccinated and vaccinated populations with disease determined by directed biopsy only. Performance of cobas HPV for ASC-US triage in pretreated SurePath specimens meets criteria for validation. Preliminary data indicate reliable performance of HPV testing in a highly vaccinated population.

Influence of co-infection complicated with human papillomavirus on cervical intraepithelial neoplasia development in patients with atypical squamous cells of undetermined significance.

Human papillomaviruses (HPV) infection is a primary cause of the development of cervical precancerous lesions and cervical cancer. However, the influence of other infections on intraepithelial neoplasia (CIN) development has not been fully elucidated. We evaluated the association between co-infection and CIN development in subjects with atypical squamous cells of undetermined significance (ASCUS). Data for ASCUS subjects who had undergone testing for high risk HPV (HR-HPV) and pathological diagnosis were analyzed. From the CIN grade, HR-HPV and vaginal infection (VI) data, both the relationship between HPV infection and CIN development and the influence of co-infection on CIN were retrospectively evaluated. Data for 56 ASCUS subjects who had undergone HR-HPV testing and cytological diagnosis were analyzed. Positive rates were HPV (73.2%), HPV16 (21.4%), HPV18 (7.1%), and HPV16 and/or 18 (26.8%). Seventeen of the subjects were diagnosed as having one or more VI pathogen; the major pathogens found were Candida spp., Gardnerella vaginalis, group B streptococcus, coagulase negative Staphylococcus, and Chlamydia trachomatis. The rate of CIN 2 or worse (≥CIN 2) was significantly higher in subjects positive for HPV16 compared with HPV negative subjects, and was significantly higher in subjects with a VI complicated with HPV compared to those without a VI. Univariate and multivariate logistic regression analysis identified positive for HPV16 and/or 18 and positive for VI to be significant variables for≥CIN 2. Our results indicate that having a vaginal infection complicated with HR-HPV affects the development of CIN in subjects with ASCUS cytology.

Optimal Follow-Up for ASC-US Cervical Cytology Remains a Balancing Act

The effect of human papillomavirus (HPV) cotesting in conjunction with cytological cervical screening remains unclear. Investigators in New Mexico (where all Pap results are linked to pathology reports) examined the outcomes of women whose initial cervical screening showed atypical squamous cells of undetermined significance (ASC-US) cytology with or without HPV testing. About 4.5% of the 457,000 women screened between 2008 and 2012 had ASC-US cytology. Of these, 80% underwent HPV testing …

Punch biopsy guided by both colposcopy and HR-HPV status is more efficient for identification of immediate high-grade squamous intraepithelial lesion or worse among HPV-infected women with atypical squamous cells of undetermined significance

ObjectivesTo investigate the accuracy of colposcopy for diagnosing high-grade squamous intraepithelial lesion (HSIL) or worse (HSIL+) in human papillomavirus (HPV)-infected patients with atypical squamous cells of undetermined significance (ASCUS) cytology, and determine whether genotyping and viral load quantitation can be useful for detecting immediate HSIL+ risk in these patients. Study designThis study included 620 cases with ASCUS and positive for high-risk (HR)-HPV within 1 month before or after cervical cytology at Qilu Hospital between February 2013 and February 2014. Based on the colposcopic impression, lesion-targeted punch biopsy, endocervical curettage biopsy or random cervical punch biopsy in four quadrants was performed on these patients within 1 month. The accuracy of colposcopy for diagnosing HSIL+ was evaluated through comparison with the biopsy results. HR-HPV status determined by Hybrid Capture 2 or HPV genotyping was analysed retrospectively as a possible predictor of HSIL+. ResultsAgreement between colposcopic impression and cervical pathology was matched perfectly in 89.2% of cases (553/620), and the strength of agreement with the κ statistic was 0.698 (p<0.001). Colposcopy had high specificity (96.9%) but low sensitivity for detecting HSIL+ (67.5%). The risk of HSIL+ was significantly higher in patients with HPV-16 infection (52.3%) than in patients infected with other types of HPV (17.9%, p<0.001). HSIL+ and virus load was correlated at cut-offs (CO) of 50 relative light units (RLU)/CO and 100 RLU/CO (p=0.024 and 0.044, respectively). If considering HPV16 infection or high virus load (at 50 RLU/CO) as a diagnostic standard of HSIL+ when colposcopic impression was negative, sensitivity was improved to 74.7% and 81.0%, respectively. ConclusionsGood agreement was found between colposcopic and pathologic diagnosis. HR-HPV genotyping or virus load is relevant to the detection of HSIL+ among HPV-infected patients with ASCUS cytology. In these patients, biopsies considering HPV-16 infection or virus load ≥50 RLU/CO may be helpful for increasing the HSIL+ detection rate.

Prevalence of High-Grade Intraepithelial Neoplasia in Patients with Cytology Presenting Atypical Squamous Cells of Undetermined Significance

Objectives: To evaluate the prevalence of histological high-grade lesions and cervical cancer in patients with ASCUS cytology. Methods: This is a cross-sectional prospective study involving 703 women with a uterus and atypical squamous cells of undetermined significance (ASCUS). The patients were submitted to a colposcopy and underwent a guided biopsy when changes on the colposcopy were detected. Results: The findings revealed 456 (64.9%) women with a normal colposcopy and 247 (35.1%) with colposcopic abnormalities. The biopsy results were: cervical intraepithelial neoplasia grade 1 (CIN 1) in 51 (20.6%) patients, CIN 2 in 11 (4.5%) patients, CIN 3 in 8 (3.2%) patients, and a negative result in 177 (71.7%) patients; no cases of cancer were detected. Tallying of 456 normal colposcopies and 177 negative biopsies yielded a total of 90.04% negative exams. Furthermore, around 7.2% (51/703) of the patients exhibited CIN 1, a lesion associated with a high potential for regression. The biopsy results were not associated with patient age or menopausal status. Conclusion: We conclude that cytological surveillance of patients with ASCUS is feasible and safe given the low risk of CIN 2/3 or cervical cancer.

Underlying Histopathology in Women with Atypical Squamous Cells of Undetermined Significance (ASC-US) Cytology in King Chulalongkorn Memorial Hospital

Objective: To determine the prevalence of underlying significant cervical lesions and factors associated with such lesions in women with atypical squamous cells of undetermined significance (ASC-US) cytology. Materials and methods: Women with ASC-US cytology undergoing colposcopy and directed biopsy at the Department of Obstetrics and Gynecology, King Chulalongkorn Memorial Hospital between January 2007 and December 2012 were reviewed. Patients’ characteristics including histopathology were collected and analyzed. Significant cervical lesions were defined as cervical intraepithelial neoplasia grade 2 (CIN2), CIN3, adenocarcinoma in situ (AIS), and invasive cervical carcinoma. Results: During the study period 154,638 Pap smears were carried out, of which 2,136 (1.38%) were ASC-US cytology. The ratio of ASC cytology/squamous intraepithelial lesions (SIL) cytology was 1.8:1. Among 2,136 women with ASC-US cytology, 627 underwent colposcopic examination and 540 had cervical biopsy. Significant cervical lesions were noted in 46 (8.6%) women. Invasive cervical carcinoma was detected in 5 (1%) women including 3 squamous cell carcinoma and 2 adenocarcinoma. Conclusions: The underlying significant cervical lesions in women with ASC-US cytology was 8.6% and approximately 1% had invasive cervical cancer. Diagnostic work-up with colposcopy is recommended. No significant factor predicting high-grade cervical lesions was noted in women with ASC-US cytology.

Cost-Effectiveness Analysis of Different Management Strategies for Detection CIN2+ of Women with Atypical Squamous Cells of Undetermined Significance (ASC-US) Pap Smear in Thailand.

To identify the optimal cost effective strategy for the management of women having ASC-US who attended at King Chulalongkorn Memorial Hospital (KMCH). An Economical Analysis based on a retrospective study. The women who were referred to the gynecological department due to screening result of ASC-US at King Chulalongkorn Memorial Hospital, a general and tertiary referral center in Bangkok Thailand, from Jan 2008 - Dec 2012. A decision tree-based was constructed to evaluate the cost effectiveness of three follow up strategies in the management of ASC-US results: repeat cytology, triage with HPV testing and immediate colposcopy. Each ASC-US woman made the decision of each strategy after receiving all details about this algorithm, advantages and disadvantages of each strategy from a doctor. The model compared the incremental costs per case of high-grade cervical intraepithelial neoplasia (CIN2+) detected as measured by incremental cost-effectiveness ratio (ICER). From the provider's perspective, immediate colposcopy is the least costly strategy and also the most effective option among the three follow up strategies. Compared with HPV triage, repeat cytology triage is less costly than HPV triage, whereas the latter provides a more effective option at an incremental cost-effectiveness ratio (ICER) of 56,048 Baht per additional case of CIN 2+ detected. From the patient's perspective, the least costly and least effective is repeat cytology triage. Repeat colposcopy has an incremental cost-effectiveness (ICER) of 2,500 Baht per additional case of CIN2+ detected when compared to colposcopy. From the sensitivity analysis, immediate colposcopy triage is no longer cost effective when the cost exceeds 2,250 Baht or the cost of cytology is less than 50 Baht (1USD = 31.58 THB). In women with ASC-US cytology, colposcopy is more cost-effective than repeat cytology or triage with HPV testing for both provider and patient perspectives.

Relevance of HPV Screening for Triaging Equivocal Cytology Findings in the Pap II-p, Pap III and Pap IIID Groups - Results of Two Long-Term Studies.

Introduction: The use of HPV screening for the triage of ASC-US (atypical squamous cells of undetermined significance) cytology results has been established as a sound standard by international trials whereas the data for other cytology findings are in part contradictory. There is a lack of long-term studies on the use of HPV triage in Germany. Materials and Methods: For the present study data from a primary HPV screening project involving women aged over 30 years, ongoing since 2006, and an epidemiological study on women aged between 20 and 27 years, ongoing since 2009, were used. Upon recruitment, all women underwent a smear test for cytology and screening for "high-risk" HPV using Hybrid Capture 2 (HC2). If both tests were positive or if there were persisting remarkable cytology findings or a positive HPV test, then clarification by colposcopy was performed. Results: Altogether, among 282 women with Pap II-p (ASC-US), Pap III (ASC-H) or Pap IIID (LSIL + CIN2) and negative HPV test there was no case of CIN3+. Among the women under 30 years of age, however, 69 % (ASC-US) to 85 % (LSIL + CIN2) of the remarkable findings were HPV positive, also among the older women with Pap IIID, the 71 % prevalence of HPV was too high for a triage and even without triage there was a 23 % risk for CIN3+. On the other hand, of the women over 30 years old with ASC-US (Pap II-p) findings, only 21 % were positive for HPV and the risk for CIN3+ in this group was high at 29 %. Also for ASC-H (Pap III) findings in the age group of over 30 years with an HPV prevalence of 56 % there was an efficient triage for CIN3+. Discussion: In summary, the HPV triage of ASC-US (Pap II-p) findings in women aged over 30 years was found to be efficient; in contrast, LSIL + CIN2 (Pap IIID) findings in this age group justified an immediate referral to colposcopy whereas cytology control appeared to be sufficient for younger women.

Clinical management of the first ASCUS report in Chile. Prospective single-cohort study.

Worldwide, there is no single strategy for optimal management of patients with ASCUS (atypical squamous cells of undetermined significance) cytology reports. The objective of this study was to determine the kind of clinical management conducted among women with a first ASCUS Pap smear report. Prospective single cohort study at a cervical pathology unit in Santiago, Chile. This was an epidemiological, descriptive, observational and quantitative follow-up study on a cohort of women with ASCUS cytological reports. In the screening phase, 92,001 cervical cytological smears were collected in primary healthcare clinics. In the diagnostic phase, all women with a first ASCUS report were selected (n = 446). These women were asked to undergo the Pap test again and it was found that 301 women had normal results, 62 women had abnormal results and 83 did not repeat the test. In the diagnostic confirmation phase, the 62 women with abnormal results underwent colposcopy and, from these results, 58 of them underwent a biopsy. The results from the biopsies showed that 16 women had negative histological reports, 13 had CIN 1 and 29 had CIN 2+. In the treatment phase, the 42 women with lesions underwent a variety of treatments, according to the type of lesion. In the post-treatment phase, cytological and colposcopic monitoring was instituted. The clinical management consisted of traditional management of screening, diagnosis, diagnostic confirmation, treatment and post-treatment monitoring.

Microbiological Infections in Women With Cervical Cytological Reports of Atypical Squamous Cells of Undetermined Significance.

To study the role of cervicovaginal infections in women with cytological reports of atypical squamous cells of undetermined significance (ASC-US). The study included 220 women admitted to the Clinic of Microscopy, Cervicovaginal and Vulvar Pathology of the Department of Gynecology and Obstetrics of the Tor Vergata University Hospital, Rome, Italy, enrolled between October 2012 and July 2013. Among the enrolled women, 105 women (47.7%) had ASC-US cytology, whereas 115 women (52.3%) had negative cytology. Microscopy showed infections more frequently in women with ASC-US than in those with negative cytology: 70.5% (74/105) vs 36% (41/115); p < .001. Cocci were present in 73.3% (77/105) of the women with ASC-US and in 43.5% (50/115) of those with negative cytology; p < .001. According to Ison score, 84% (88/105) of ASC-US was grade 0 vs 22% (25/115) of negative cytology, p < .001. Human papillomavirus was detected in 35% of the women with ASC-US. A statistically significant correlation between high pH and vaginal infections was found in women aged 20 to 29 (p = .003) and those 50 years or older in both cytological report groups; p < .001. Cervicovaginal infections are associated with a cytological report of ASC-US. Direct microscopy of vaginal specimens allowing immediate evaluation of the vaginal microflora and infectious agents may be a useful tool in managing women with cytological reports of ASC-US.

The reliability of high-risk human papillomavirus detection by Aptima HPV assay in women with ASC-US cytology

BackgroundThe Aptima HPV assay (AHPV) for high-risk human papillomavirus (hrHPV), and the Aptima HPV 16 18/45 Genotype assay (AHPV GT) for HPV16 and for HPV18 and/or HPV45 (HPV18/45) genotypes are approved for cervical cancer screening by the U.S. Food and Drug Administration. There are limited data on the reliability of these tests for detection of hrHPV, HPV16, and HPV18/45. ObjectivesTo assess the reliability of AHPV and AHPV GT on paired specimens from women with atypical squamous cells of undetermined significance (ASC-US) cytology. Study designIn a population of women with ASC-US cytology (n=988), cervical specimens were collected at a routine screening baseline visit and at the colposcopy visit that occurred a median of 29 days later. Specimens were tested by AHPV and if positive, by AHPV GT. ResultsThere was no significant difference in the percent AHPV positive between the colposcopy and baseline specimens (41.9% vs. 43.0%, respectively, p=0.3). The percent agreement, percent positive agreement, and the kappa value were 88.6%, 76.3%, and 0.766, respectively. There were no significant differences between AHPV testing of the colposcopy and baseline specimen in the sensitivity (95.2% vs. 92.9%, respectively, p=1) and specificity (60.5% vs. 59.2%, respectively, p=0.3) for CIN3+. Comparing the hierarchical AHPV and AHPV GT results on the two specimens, the percent exact agreement was 86.2%, the percent positive agreement was 68.4%, and the kappa value was 0.746. ConclusionsAHPV and AHPV GT demonstrated good reliability for hrHPV detection and risk stratification.

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.

Detection of human papillomavirus 16, 18, and 45 in women with ASC-US cytology and the risk of cervical precancer: results from the CLEAR HPV study.

The Aptima human papillomavirus (HPV) 16 18/45 Genotype (GT) assay (AHPV-GT) is a qualitative E6/ E7 oncogene messenger RNA test that detects HPV 16 and a pool of HPV 18 and 45. The CLEAR (Clinical Evaluation of APTIMA mRNA) study was the pivotal, prospective, multicenter US clinical study to validate the Aptima HPV (AHPV) assays. In this analysis, we evaluated the clinical performance of AHPV and AHPV-GT assays for detection of cervical intraepithelial neoplasia grade 2 or more severe (CIN2 +) and grade 3 (CIN3) or adenocarcinoma in situ in 912 women with atypical squamous cells of undetermined significance (ASC-US) Papanicolaou result. The AHPV-GT assay was performed on high-risk HPV (hrHPV) positives as determined by the AHPV assay. Overall, the percent positive for hrHPV was 38.8% (354/912), of which 34.2% (121/354) were GT positive. Among hrHPV-positive women, the risks of CIN2 + were 37.0% for HPV 16 positives, 15.9% for HPV 18/45 positives, 14.3% for other hrHPV positives, and 2.2% for AHPV negatives. The risks of CIN3 + were 20.5% for HPV 16 positives, 9.1% for HPV 18/45 positives, 4.3% for other hrHPV positives, and 0.7% for HPV negatives. We demonstrated that AHPV-GT is a reliable and effective test for cervical cancer risk stratification in women with an ASC-US cytology diagnosis.

Performance of HPV DNA testing with hybrid capture 2 in triaging women with minor cervical cytologic abnormalities (ASC-US/LSIL) in Northern Thailand.

Minor cervical cytologic abnormalities include atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL). Approximately 10-20% of women with minor cytologic abnormalities have histologic high-grade squamous intraepithelial or worse lesions (HSIL+). In Thailand, women with minor cytologic abnormalities have a relatively high risk of cervical cancer, and referral for colposcopy has been suggested. A triage test is useful in the selection of women at risk for histologic HSIL+ to reduce the colposcopy burden. The aim of this study was to assess the performance of high-risk HPV DNA test in triage of women with minor cytologic abnormalities in northern Thailand. All women with ASC-US/LSIL cytology who were referred to our colposcopy clinic from October 2010 to February 2014 were included. HPV DNA testing was performed using Hybrid Capture 2 (HC2). All patients received colposcopic examination. Accuracy values of HC2 in predicting the presence of histologic HSIL+ were calculated. There were 238 women in this study (121 ASC-US and 117 LSIL). The HC2 positivity rate was significantly higher in the LSIL group than in ASC-US group (74.8% versus 41.0%, p<0.001). Histologic HSIL+ was detected in 9 women (7.4%) in the ASC-US group and 16 women (13.7%) in the LSIL group (p=0.141). There was no histologic HSIL+ detected among HC2-negative cases (sensitivity and negative predictive value of 100%). The performance of HC2 triage was highest among women aged >50 years with ASC-US cytology. An increase in the cut-off threshold for positive HC2 resulted in a substantial decrease of sensitivity and negative predictive value. HPV DNA testing with HC2 shows very high sensitivity and negative predictive value in triage of women with minor cervical cytologic abnormalities in northern Thailand. An increase of the cut-off threshold for HC2 triage is not recommended in this region.

Clinical significance of ASCUS and ASC-H cytological abnormalities: a six-year experience at a single center.

To evaluate colposcopic biopsy results of patients with cervical cytological findings of atypical squamous cells of undetermined significance (ASC-US) and atypical squamous cells with high-grade lesions that cannot be excluded (ASC-H). A retrospective evaluation of data from 358 patients, who had cervical cytological findings of ASC-US (n = 335) and ASC-H (n = 23), and had colposcopic assessments between 2005 and 2011. Cervical biopsy results of patients diagnosed with ASC-US cytology (n = 335) revealed cervical squamous cell carcinoma 0.9 % (n = 3) at biopsy, cervical intraepithelial neoplasia 3 (CIN 3) in 3.8 % (n = 13), cervical intraepithelial neoplasia 2 (CIN 2) in 1.1 % (n = 4), cervical intraepithelial neoplasia 1 (CIN 1) in 35.2% (n = 118), and benign lesions in 59 % (n = 197). Cervical biopsy results of patients diagnosed with ASC-H cytology (n = 23) revealed CIN 3 at biopsy in 39.3% (n = 9), CIN 2 in 21.7% (n = 5), CIN 1 in 26% (n = 6), carcinoma in situ in 8.7% (n = 2), and squamous cell cancer in one patient (4.3%). The cytological diagnosis of ASC-US may lead to the diagnosis of cervical intraepithelial lesion of higher grades as well as cervical cancer and should be evaluated by colposcopic cervical biopsy.

Type-Specific Human Papillomavirus Testing for the Follow-up of Women with a Typical Squamous Cells of Undetermined Significance (ASCUS) Pap Smears

Background: The aim of our study was to assess the prevalence of Human papillomavirus (HPV) genotypes amongst women diagnosed with Atypical Squamous Cells of Undetermined Significance (ASC-US) Pap smears in southern France and to determine whether the systematic application of HPV genotyping in this patient population could improve the ability to identify women with a higher or lower risk of progression to cervical cancer or CIN2 or 3. The ultimate goal is to limit the number of colposcopy performed unnecessarily in women with ASC-US cytology. Methods: We performed a retrospective study of HPV genotype distribution in 313 ASC-US Pap smears from women who attended at the University Hospital of Nice between 2008 and 2012. We analysed by logistic regression the progression of cervical lesions correlating with the genotypes identified. Results: We observed a high prevalence of HPV 16 (12%), 31 (7%), 51 (7%), 53 (7%), 56 (7%), 52 (5%), 66 (5%), 68 (5%), and 58 (4%) among HR HPV identified in ASC-US smears. Infection with one of the HPV genotypes 16, 18, 31, 33, 45, 52, 58, or 68 was associated with a 3.4-fold higher risk (95% CI [1.20-9.94]) of discovering a CIN2 or 3 lesion at biopsy. Furthermore HPV16 mono- and poly-infections increased this risk by 7.1-fold (95% CI [2.1-24.52]). No correlation between age and severity of lesion was observed in our study. Conclusion: The results from this preliminary study suggests an increased risk to develop CIN2 or 3 in women with ASC-US cytology associated with 8 HR HPV genotypes (16, 18, 31, 33, 45, 52, 58, 68). This observation suggests the systematic use of HPV genotyping to improve the management of patients with ASC-US and must be completed by a large international prospective study.

Clinical significance of atypical squamous cells of undetermined significance in detecting preinvasive cervical lesions in post- menopausal Turkish women.

To evaluate the clinical significance of atypical squamous cells of undetermined significance (ASCUS) in PAP test in post-menopausal women and compare with reproductive age women. A total of 367 patients who referred to our gynecologic oncology clinic were included to the study between September 2012 and August 2013. Data for 164 post-menopausal (group 1) and 203 pre-menopausal (group 2) women with ASCUS cytology were evaluated retrospectively. Immediate colposcopy and endocervical curettage was performed for both groups and conization for all women with a result suggestive of CIN2-3. Histopathological results and demographic features of patients were compared between the two groups. Mean age of the patients was 54.6±6.5 years in group 1 and 38±6.6 years in group 2. Some 14 (8.5%) of post- menopausal women and 36 (17.7%) of pre-menopausal women were current smokers (p=011). Totals of 38 (23.2%) post-menopausal and 64 (31.5%) pre-menopausal women were assessed for HPV-DNA. High risk HPV was detected in 7 (4.3%) and 21 (10.3%), respectively (p=0.029). Final histopathological results recorded were normal cervix, low grade cervical intra-epithelial neoplasia (CIN 1), and high grade cervical intra-epithelial neoplasia (CIN2-3). In group 1 results were 84.8%, 12.2% and 1.8%, respectively, and in group 2 were 71.9%, 23.2% and 4.9%. There were no cases of micro invasive or invasive cervical carcinoma in either group. Two cases were detected as endometrial carcinoma in the menopausal group (1.2%). In current study we found that preinvasive lesions were statistically significantly higher in pre-menopausal women than post- menopausal women with ASCUS. Cervicitis was more common in menopausal women. Therefore, we think that in case of ASCUS in a post-menopausal woman there is no need for radical management.