ASC-H Cytology Research Articles

Genotype profile of HPV in ASC-H cytology and histologic follow-up-prevalence, distribution, and risk: A retrospective study of 1414 cases.

A cytologic diagnosis of atypical squamous cells, cannot exclude high-grade squamous lesion (ASC-H) poses a disproportionately high risk of cervical cancer development. The objective of this study was to analyze type-specific risks by mapping human papillomavirus (HPV) genotypes in ASC-H cytology. In total, 1,048,581 Papanicolaou tests that had ASC-H cytology were retrieved. Concurrent HPV genotyping using proprietary multiplex real-time (MRT) and polymerase chain reaction (PCR) HPV tests and histologic follow-up findings were analyzed. Among 1678 patients who had ASC-H findings (0.16%), 1414 (84.3%) underwent concurrent HPV genotyping (MRT, 857; HPV PCR test, 557). The overall high-risk HPV (hrHPV)-positive rate was 84.4%. Of the 857 MRT cases, 63.9% were infected with a single hrHPV, and 24.4% had multiple genotypes. The most prevalent HPV types were HPV16/52/58/33/31. Lesions that were identified as cervical intraepithelial neoplasia 2 or worse (CIN2+) were detected in 498 of 906 cases (55.0%), including 81 cervical carcinomas (8.9%). The risk of CIN2+ for the composite group of HPV16/52/58/33/31-positive cases was 62.7%, representing 90.7% (264 of 291) of total CIN2+ lesions in ASC-H/hrHPV-positive cases by MRT. CIN2+ lesions were detected in 108 of 142 (76.1%) HPV16-positive and/or HPV18-positive women by the PCR the HPV test. Among 128 hrHPV-negative ASC-H cases by both methods, CIN2+ lesions were identified in 21 of 128 (16.4%), including five cervical carcinomas (3.9%). The sensitivity, specificity, positive predictive value, and negative predictive value for patients in the composite group with HPV16/52/58/33/31 were 88.0%, 40.8%, 62.7%, and 75.0%, respectively. Papanicolaou tests classified as ASC-H are associated with a high CIN2+ rate and warrant colposcopy, regardless of HPV status. The extent to which the risk-stratification provided by comprehensive HPV genotyping can inform the management of ASC-H cytology remains to be explored.

Conservative management of cervical intraepithelial neoplasia 2 and prediction of its progression - a retrospective study.

Cervical intraepithelial neoplasia 2 (CIN2) evolution is controversial, and some of them regress spontaneously in a two-year follow-up. The purpose of this work was to evaluate the percentage of CIN2 progression or persistence during a 24-month follow-up, using clinical predictors such as human papillomavirus (HPV) genotype and cytology results. This is a retrospective case-control study and included patients of reproductive age who had a new diagnosis of CIN2 who were monitored for lesion regression (Group 1, n=72 patients), and progression or persistence (Group 2, n=36 patients). A multinominal logistic regression was preferred to evaluate the impact that various categorical risk elements can lead to outcomes of persistence or progression of CIN2. We also performed a linear regression to assess the risk of CIN2 progression or persistence using the interaction between clinical predictors. A previous cervical cytology indicative of high-grade squamous intraepithelial lesion (HSIL) [relative risk ratio (RRR): 3.85, 95% confidence interval (CI): 1.66-8.90] or atypical squamous cells, cannot exclude HSIL (ASC-H) can highly raise the probability of a CIN2 progression or persistence. The presence of HPV16 increased the risk of CIN2+ with 3.77 (95% CI: 0.78-5.00), the presence of HPV18 increased the probability of CIN2+ with 4.39 (95% CI: 1.35-14.33), and other high-risk HPV (HR-HPV) strains increased the probability of CIN2+ with 3.62. The highest risk issue was produced by the interaction between HSIL* HPV16, ASC-H* HPV16, and ASC-H* HPV18. When discussing follow-up for CIN2 lesions, it is important to offer careful consideration and monitoring of patients with a previous HSIL or ASC-H cytology, with or without HPV 16, 18 or other HR-HPV strains, as their presence significantly increased the risk of CIN2 progression and persistence.

Type distribution of human papillomaviruses in ThinPrep cytology samples and HPV16/18 E6 gene variations in FFPE cervical cancer specimens in Fars province, Iran

BackgroundThere exists strong evidence that human papillomavirus (HPV) is associated with cervical cancer (CC). HPV E6 is a major oncogene whose sequence variations may be associated with the development of CC. There is not sufficient data on the distribution of HPV types in ThinPrep cytology specimens and HPV 16/18 E6 gene variations among CC patients in the southwest of Iran. This study was conducted to contribute to HPV screening and vaccination in Iran.MethodsA total of 648 women screened for cervicitis, intraepithelial neoplasia or CC were included in the study. All participants underwent ThinPrep cytology testing, single-step HPV DNA detection and allele-specific reverse hybridization assays. Moreover, a total of 96 specimens previously tested positive for single infection with HPV16 or 18 were included for variant analysis. HPV16/18 lineages and sublineages were determined by PCR assays followed by sequencing the E6 gene and the construction of neighbor-joining phylogenetic trees.ResultsOverall, HPV DNA was detected in 62.19% of all the screened subjects. The detection rates of HPV DNA among individuals with normal, ASC-US, ASC-H, LSIL, and HSIL cervical cytology were 48.9%, 93.6%, 100%, 100%, and 100%, respectively. Low-risk HPVs were detected more frequently (46.9%) than high-risk (38.9%) and possible high-risk types (11.1%). Of 403 HPV-positive subjects, 172 (42.7%) had single HPV infections while the remaining 231 (57.3%) were infected with multiple types of HPV. Our results indicated a remarkable growth of high-risk HPV66 and 68 and low-risk HPV81 which have rarely been reported in Iran and HPV90 and 87 that are reported for the first time in the country. In addition, 3 lineages (A, D, and C) and 6 sublineages (A1, A2, A4, C1, D1, and D2) of HPV16, and one lineage and 4 sublineages (A1, A3, A4, and A5) of HPV18 were identified. The studied HPV16 and 18 variants mainly belonged to the D1 and A4 sublineages, respectively.ConclusionThe present study suggests that the prevalence of HPV infection in women of all age groups with or without premalignant lesions in the southwestern Iran is high and the predominant HPV types in the southwest of Iran may differ from those detected in other parts of the country. This study also highlights the necessity of not only initiating HPV vaccination for the general population but also developing new vaccines that confer immunity against the prevalent HPV types in the area and national cervical screening programs using a combination of thinPrep cytology test and HPV detection assays in order to improve the accuracy of the screening.

Predictors of CIN2+ in Patients with PAP III-P (ASC-H): A Cross-Sectional Study

This study aims to investigate whether specific characteristics of the patient group with ASC-H (PAP III-p) findings increase the likelihood of clinically significant disease (CIN2+), offering implications for risk-adapted clinical management. 225 patients with an ASC-H smear presenting to our colposcopy unit between 2014 and 2021 were identified and examined retrospectively. A total of 203 patients were included in the cross-sectional study using multivariate logistic regression. Of the 12 variables that entered the regression model, transformation zone (p = 0.045) and HPV infection (p = 0.005) contributed significantly to predicting CIN2+. A T3 transformation zone had a protective effect, reducing the likelihood of significant pathology. Infection with HPV high risk (non 16/18) or HPV high risk (16/18), on the contrary, increased the likelihood of CIN2+ four times and seven times, respectively, compared to the lower-risk category. A differential approach in the workup of ASC-H cytology is advisable. Younger, premenopausal patients with positive HPV high-risk findings are at a significantly higher risk for CIN2+ lesions than older postmenopausal women with negative high-risk HPV test results. As the risk increases from HPV high-risk non 16/18 to HPV 16/18 infections, using HPV PCR testing is advisable.

The Hybrid Capture 2 Results in Correlation with the Pap Test, Sexual Behavior, and Characteristics of Romanian Women.

Human papillomavirus (HPV) infection is the major cause of cervical cancer (CC); hence, it is critical to understand the processes by which HPV infection causes squamous intraepithelial lesions, as well as the proper diagnostic tools. The objective of this study was to establish the correlations between Pap test results and Hybrid Capture 2 (HC2) tests findings. This study included 169 women between the ages of 30 and 64, who presented for consultation in gynecological clinics in both the public and the private sectors. These women reported symptoms, such as abnormal vaginal discharge and genital irritation, as well as early onset of sexual activity, multiple sexual partners, history of other sexually transmitted infections or high-risk sexual partners, immunosuppression, or tobacco smoking. Pap tests and HPV testing, using the HC2 method, were performed for the women enrolled in the study, including data gathered after patients completed questionnaires concerning their sexual behavior. The HC2 method revealed that 66 patients (39.1%) tested positive for high-risk HPV types. Of the patients with positive results, 14 (21.2%) presented Atypical Squamous Cells of Undetermined Significance (ASC-US) compared to 10 (9.7%) patients in the negative group (p = 0.042). Atypical Squamous Cells for which a high-grade lesion cannot be excluded (ASC-H) were identified primarily in women with positive HC2 (6.1%). HR-HPV positivity was substantially more associated with low-grade ASC-US or low-grade squamous intraepithelial lesion (LSIL) and high-grade ASC-H cytology (OR = 2.53; 95% CI: 1.10-5.80, respectively, OR = 14.9; 95%CI: 1.006-34.59). Unmarried women (31.8%; p = 0.004) and women with multiple partners (over four partners, 10.6%; p = 0.03) were more likely to have an HPV infection when compared to married women and those with fewer sexual partners. Understanding the epidemiology of HPV genital infections is essential for developing preventive measures against this infection and CC. Identifying the most prevalent HPV types, and determining the incidence of HPV oncogenic infections, in conjunction with Pap test results and sexual behavior information, can constitute part of an algorithm for the efficient management of cervical intraepithelial lesions.

High-risk HPV testing improves accuracy in detection of CIN2+ lesions in ASC-H postmenopausal women? An academic hospital experiences.

Reflex human papilloma virus (HPV) testing with "atypical squamous cells, cannot exclude high-grade squamous lesion (ASC-H)" cytologic diagnosis is not recommended by American Society for Colposcopy and Cervical Pathology guidelines. Studies have shown human papillomavirus (HPV)-negative ASC-H patients of increased age are low risk for cervical intraepithelial neoplasia 2 or worse (CIN2+) lesions on colposcopic follow-up. We retrospectively assessed the efficacy of reflex HPV testing in postmenopausal women with ASC-H in the Los Angeles County hospitals and clinics in a 5-year period. Of a total 85 clinically postmenopausal women with ASC-H, 31 (36.5%) women were found to have CIN2+ lesions on follow-up biopsy and five of them were HPV-negative. Of the women with CIN2+ lesions and positive HPV, 13 (41.9%) were high-risk HPV (hrHPV) 16/18/45 positive and 13 (41.9%) were hrHPV-other subtype positive. Women with positive HPV had an over 3-fold increased risk of developing CIN2+ lesions (P= 0.008). Relative risk of hrHPV16/18/45 was 1.79-fold higher than that of hrHPV-other subtype. The positive predictive value and negative predictive value of hrHPV were 49.1% and 84.4%, respectively. CIN2+ detection rate in Hispanic women with positive hrHPV was higher than in non-Hispanic women (53.8% versus 35.7%). Overall, postmenopausal women with ASC-H cytology result and negative hrHPV were less likely to develop CIN2+ lesions, whereas about half of ASC-H postmenopausal women develop CIN2+ lesions if hrHPV positive, especially if hrHPV 16/18/45 positive. Therefore, triaging ASC-H postmenopausal women with cotesting or, ideally, hrHPV genotyping should be considered as optimal clinical practice to avoid overtreatment.

P16/Ki-67 Dual Staining in Positive Human Papillomavirus DNA Testing for Predictive Diagnosis of Abnormal Cervical Lesions in Northeastern Thai Women.

Cervical cancer screening can effectively reduce new cervical cancer cases, including in Thailand. The abnormal results are subsequently referred for colposcopy. To avoid unnecessary colposcopy, an efficient triage is still needed for validation. This study aimed to investigate the overall positivity of cytology-based screening, HPV detection, and p16/Ki-67 dual staining and evaluate different triage strategies for predictive diagnosis of abnormal cervical lesions in northeastern Thailand. Cervical cells were collected from 191 women who came for cervical screening in the gynecological outpatient department during March 2019-February 2020. Pap smear samples were classified into 6 groups including 17 atypical glandular cells (AGC), 21 atypical squamous cells of undetermined significance (ASC-US), 7 atypical squamous cells - cannot exclude HSIL (ASC-H), 26 low-grade squamous intraepithelial lesions (LSILs), 19 high-grade SILs (HSILs) and 101 no squamous intraepithelial lesion (noSIL). Polymerase chain reaction (PCR) was performed for HPV DNA detection. HPV genotyping was determined by reverse line blot hybridization. P16/Ki-67 dual staining was performed by using CINtec PLUS Cytology kit. Biopsies from abnormal screening were collected for surgical pathology classification. High-risk HPV (HR-HPV) infection was 2.97%, 29.41%, 38.10%, 57.14%, 46.15% and 84.21% in noSIL, AGC, ASC-US, ASC-H, LSIL and HSIL cytology respectively. P16/ Ki-67 in noSIL, AGC, ASC-US, ASC-H, LSIL and HSIL was 0.99%, 5.88%, 9.52%, 42.86%, 26.92% and 63.16%, respectively (P-value < 0.001). Among p16/Ki-67 positive cases, 96.15% (25/26) were infected with HPV and 84.62% (22/26) were HR-HPV. The overall positivity of each and co-testing between cytology or HPV DNA testing or p16/Ki-67 dual staining was evaluated. In each cervical lesion, primary HPV DNA testing showed the highest sensitivity, but low specificity. The combined all HPV/HR-HPV with p16/Ki-67 detection increased the specificity of abnormal cervical lesions. P16/Ki-67 dual stain cytology in HPV-positive women performs well for diagnosis of abnormal cervical lesions and should be considered for management of HPV-positive women to avoid unnecessary colposcopy referrals.

Detection of high‐grade cervical disease among women referred directly to colposcopy after a positive HPV screening test varies with age and cytology findings

Australia's new HPV-based cervical screening program is based on an algorithm that incorporates reflex cytology to guide decisions about further follow-up with colposcopy and, if indicated, biopsy. We reviewed results for 2300 women referred directly for colposcopy after their first positive HPV screening test, to determine the proportion that had underlying histological high-grade abnormality (HGA). Overall, HGA was detected in 24.3% of women. Among HPV16/18 positive women, 18.0% had HGA, increasing from 6.6% among women with negative cytology to 79.7% among women with high-grade squamous lesion or worse, or any glandular lesion on cytology (HSIL+; P-trend < .001). For this latter group, the proportion with HGA was higher among HPV16/18 positive women than among those positive for other oncogenic types (68.8%; P = .029). Among women with ASC-H cytology, 51.8% had HGA, with no difference between HPV groups (P = .314). In analyses by age-groups, detection of HGA was highest, at 36.4%, among women younger than 35 years, then decreased significantly to 5.9%, among women aged 65 to 74 years (P-trend < .001). The relationship of decreasing HGA detection with increasing age was strong for women with negative cytology, and those with ASC-H cytology (P-trend < .001 for each). For women with HSIL+ cytology, detection of HGA was high and stable, regardless of age (P-trend = .211). This report describes the first follow-up colposcopy findings in Australia's new HPV-based cervical screening program. The results demonstrate the additional value of reflex cytology in managing HPV positive women and suggest that further refinement of the risk-based algorithm to account for age may be warranted.

Colposcopic and Histological Outcome of Atypical Squamous Cells of Undetermined Significance and Atypical Squamous Cell of Undetermined Significance Cannot Exclude High-Grade in Women Screened for Cervical Cancer.

Objectives:The objectives of the study are to assess the prevalence of colposcopic and histological abnormalities in patients diagnosed with ASCUS and ASC-H and to compare the prevalence of CIN in each group. Methods:Population-based cross-sectional retrospective study was conducted in one of tertiary hospitals in UAE. All cervical smears reported as ASCUS or ASC-H in 2015 were included in this study. The local guideline in 2015 was to refer all cases of ASC for colposcopy assessment. Results:Overall 7,418 cervical smears were processed at our laboratory service, 5.6% (n=413) were reported as ASC. 95% of them (n=394) were ASCUS and 5% (n=19) were ASC-H. The overall prevalence of high grade CIN in patients with ASC-H is 26% compared with 0.8% for patients with ASCUS regardless the age. The relative risk of patients with ASC-H is 8 folds higher than patients with ASCUS to have low grade CIN but 29 fold higher risk of having High grade CIN and the P value =0.0001.Conclusion:ASC-H cytology confers a substantially higher risk for high grade CIN than ASCUS regardless of age. HPV test is an important triage test in patients with ASCUS to predict cellular changes and CIN.

“Three-Step Approach” Versus “See-and-Treat Procedure” in women with “High Grade Squamous Intraepithelial Lesion” (HSIL) or “Atypical Squamous Cells cannot exclude HSIL” (ASC-H) Cytology

Objective: The purpose of this study was to examine the correlation between histological findings in women with HSIL or ASC-H who have undergone loop electrosurgical excisional procedure with “Three-Step Approach” and “See-and-Treat Procedure".Study Design: A retrospective review was performed in 171 women with cytologically detected HSIL or ASC-H. Sixty five women with HSIL cytology and 35 women with ASC-H cytology were managed by “Three-Step Approach”, 35 women with ASC-H and 36 women with HSIL cytology were managed by "See-and-Treat Procedure”. Rates of histopathological findings were compared in two strategies with respect to previous cytology.Results: Fifteen women with ASC-H (42.9%), and 24 women with HSIL (68.5%) had CIN 2-3 at loop electrosurgical excisional procedure specimens in the “See-and-Treat” group whereas 14 women with ASC-H (38.8%), and 43 women with HSIL (66.2%) had CIN 2-3 at loop electrosurgical excisional procedure specimens in the “Three-Step Approach” group. There was no significant difference in the rate of CIN 2+ lesions when two strategies were compared in women with HSIL and ASC-H (p=0.71 and p=0.72, respectively). The overtreatment rates were 22.9% and 48.6% for HSIL and ASC-H cytology, respectively in the “See and Treat” group.Conclusion: In the ASC-H group, the rate of CIN 2+ lesions is significantly high (51.4%). It seems rational to perform “See-and-Treat procedure” in the setting of ASC-H smears although the overtreatment rate seems to be high. Because of the rate of overtreatment, the “Three-Step Approach” seems to be more reasonable in women with ASC-H cytology who also have fertility concerns. After a cytological diagnosis of HSIL, “see and treat” approach seems to be a safe and time saving strategy.

The Significance of LSIL Cells and High Risk HPV Testing in ASC-H Cytology for Predicting CIN2+ Anal and Cervical Lesions

The Significance of LSIL Cells and High Risk HPV Testing in ASC-H Cytology for Predicting CIN2+ Anal and Cervical Lesions

ASC-H cytological result: clinical relevance and accuracy of colposcopy in predicting high-grade histological lesions—a 7-year experience of a single institution in Portugal

Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) represents an interpretative challenge in clinical practice. We aimed to evaluate the histological outcome of ASC-H cytology and to evaluate the accuracy of colposcopy in predicting high-grade histological lesions. Retrospective study of ASC-H cervical cytology results, from January 2010 to December 2016, at a tertiary hospital. Demographic characteristics, colposcopic findings, diagnostic procedures, and histological outcomes were analyzed using SPSS, version 22.0. ASC-H prevalence was 0.25%. Patient mean age was 42.02 ± 12.8 years. The overall incidence of cervical dysplasia of any grade was 83.6% (n = 56) and the incidence of high-grade lesions was 50.8% (n= 34) (including 1 case of in situ adenocarcinoma and 2 cases of squamous cell carcinoma). Among patients with type 1 or 2 transformation zone (TZ), 84.9% (n = 45) had abnormal colposcopic findings, with 62.2% (n = 28) corresponding to grade 2 and 37.8% (n = 17) to grade 1. Colpo-histologic concordance was 85.4% (82.1% for grade 2 lesions and 100% for grade 1 lesions). The sensitivity, specificity, positive predicted value (PPV) and negative predictive value (NPV) was 100%, 75%, 82.1%, and 100%, respectively. The histological study of patients with type 3 TZ revealed 45.8% (n = 11) of high-grade lesions. ASC-H is strongly associated with high-grade histological lesions. Immediate evaluation of patients with this cytology abnormality is therefore mandatory. Colposcopy, when performed by expert clinicians, has great accuracy in detecting high-grade lesions. Histological evaluation of patients with type 3 TZ is extremely important because almost 50% of patients have this type of lesion.

Overall accuracy of cervical cytology and clinicopathological significance of LSIL cells in ASC-H cytology.

The aims of this study were (i) to investigate the diagnostic accuracy of Papanicolaou (Pap) smears and (ii) to evaluate the clinicopathological significance of the presence of low-grade squamous intraepithelial lesion (LSIL) cells in atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (HSIL) (ASC-H) cytology. We retrospectively reviewed paired cytological and histological findings from 3141 patients. ASC-H cytology was classified as either ASC-H or LSIL with some features suggestive of the presence of a concurrent HSIL (LSIL-H). Clinicopathological characteristics were evaluated through a retrospective study and meta-analysis. The accuracy of the cytological diagnosis was 93.7% (2942 of 3141 cases). The positive predictive value (PPV) of ASC-H for cervical intraepithelial neoplasia grade 2 or worse (CIN 2+ ) was 51.4%. In cases of LSIL-H, CIN 2+ histology was more prevalent in the pre-menopausal period (19-44 years) than in peri- and postmenopausal periods (older than 45 years) (P = 0.024). There was no difference in the ability of LSIL-H and ASC-H to predict CIN 2+. The Pap smear is a good cervical cancer screening method. Although there was no difference in the predictive value for CIN 2+ between LSIL-H and ASC-H, the presence of definite LSIL cells was more predictive of CIN 2+ in younger patients than in older patients.

Reflex Human Papillomavirus Test Results as an Option for the Management of Korean Women With Atypical Squamous Cells Cannot Exclude High-Grade Squamous Intraepithelial Lesion.

Current guidelines recommend initial colposcopy with biopsy regardless of human papillomavirus (HPV) test results in women with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H). The purpose of this study was to evaluate the value of HPV testing in women with ASC-H based on colposcopic pathology results. A multicenter cross-sectional study was carried out at three academic hospitals and involved 40,847 Korean women who underwent cervical cancer screening with cytology and HPV tests with or without subsequent colposcopic biopsies between January 2007 and December 2013. ASC-H was diagnosed in 276 women (0.7%). Only 6 of 68 (8.8%) women with ASC-H who were HPV negative had cervical intraepithelial neoplasia grade ≥2 (CIN ≥2) lesions, whereas 47.4% of the women with ASC-H who were HPV positive had CIN ≥2 lesions. No cases of invasive cervical cancer were diagnosed among women with ASC-H who were HPV negative. Logistic regression analysis was performed using the group with normal Papanicolaou test results and HPV-negative status as the reference group. Women with ASC-H who were HPV positive had a significantly increased risk of CIN ≥2 lesions, whereas no significant increase was observed in patients with ASC-H and HPV-negative status. If the result of the HPV test was negative, the risk of CIN ≥2 lesions in Korean women with ASC-H cytology was low. Reflex HPV testing should be an option for the management of women with cytology showing ASC-H to decrease unnecessary colposcopic biopsies, which are expensive and invasive. Current American Society for Colposcopy and Cervical Pathology guidelines recommend universal colposcopy for the management of women with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) on cytology, regardless of human papillomavirus (HPV) test results. The present study suggested that HPV cotesting in patients with ASC-H cytology can provide more detailed and useful information regarding the risk of high-grade cervical intraepithelial neoplasia (CIN) lesions and the need for further treatment. When the result of the HPV test was negative, the risk of CIN lesions of grade ≥2 in women with ASC-H cytology was low. Consequently, reflex HPV testing, rather than immediately performance of invasive and expensive colposcopy with biopsy, should be an option for the management of women with ASC-H.

HPV testing results and histologic follow-up in women with ASC-H cytology in different age groups

Assessment on human papillomavirus (HPV) testing and disease outcome of atypical squamous cell, cannot exclude high grade squamous intraepithelial lesion (ASC-H) in different age groups is limited in published reports. We reviewed our experience over a 5-year period on ASC-H cytology and correlated age distribution with high-risk HPV (HR-HPV) status and histological follow-up in a large cohort study. Women with ASC-H cytology were retrieved from the hospital database. HR-HPV status and histological diagnoses on cervical biopsy or loop electrosurgical excisional procedure specimens were reviewed and correlated to 5 age groups. Ages of women with ASC-H ranged from 16 to 88 years, with 42% women <30 years and 58% women >30 years. Among 647 cases diagnosed as ASC-H, 96% (618) had HR-HPV testing results, including 68.2% HR-HPV positive and 31.8% HR-HPV negative. HR-HPV positivity of ASC-H gradually decreased from 95.2% in women <20 years to 40.6% in the age group >51 years. Histologic follow-ups were available for review in 80% (517) of the cases. Cervical intraepithelial neoplasia, grade 2 or higher (CIN2+) lesions were found in 40.3% (208) cases, including 92.9% women with HR-HPV-positive/ASC-H and 7.1% of women with HR-HPV-negative/ASC-H. The detection rate of CIN2+ by ASC-H gradually decreased from 51.2% in women <20 years to 18.2% in women >51 years. The majority of postmenopausal women with HR-HPV-negative/ASC-H had atrophy-related change. The specificity of ASC-H cytology in detection of cervical CIN2+ lesions is age-dependent: higher in younger women <30 years, but gradually decreased in women >30 years. The vast majority (93%) of CIN2+ lesions were seen women with HR-HPV-positive/ASC-H. HR-HPV testing improves the accuracy and specificity in women with ASC-H in almost all age groups, especially in age groups older than 40 years.

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.

Dual immunostaining of cervical cytology specimens with atypical squamous cells for p16/Ki-67 does not exclude the existence of a high-grade squamous intraepithelial lesion

This study was conducted to evaluate the accuracy of p16/Ki-67 dual immunostaining compared to high-risk human papillomavirus (HR-HPV) DNA testing for cervical intraepithelial neoplasia (CIN) in women with atypical squamous cells, cytology not excluding high-grade squamous intraepithelial lesion (ASC-H). Data were collected from 73 patients diagnosed to have ASC-H on a Pap smear who were HPV genotyped and had histological examination of a cervical biopsy. The CINtecPLUS kit was used on residual liquid-based material, and the immunoreactivity of dual-stained cells was graded according to the number as follows: G1 (1-5 positive cells), G2 (6-10), G3 (11-20), and G4 (> 20). Accuracy was evaluated based on the histological examination of colposcopy-guided biopsy or cervical conization on follow-up. Of the 70 patients with available data, positive p16/Ki-67 was associated with histological severity as follows: 15% in negative histology, 67% in CIN 1, 90% in CIN 2, and 100% in CIN 3. The average grade of positive p16/Ki-67 staining also increased from 0.2 in histologically negative cases to 1.2 in CIN 1, 2.4 in CIN 2, and 2.9 in CIN 3 (p < 0.01). For patients with CIN 2 or higher, p16/Ki-67 had a sensitivity of 94.6% and a specificity of 75.8%, while HR-HPV testing showed a sensitivity of 67.6% and a specificity of 66.7%. p16/Ki-67 immunostaining demonstrated better accuracy than HR-HPV for detecting CIN 2 or higher in patients with ASC-H cytology. Given the higher concordance with histological diagnosis, the grading system of positive p16/Ki-67 can be a useful adjunct for predicting high-grade lesions in clinical practice.

Updates of the current screening guidelines for the early detection of cervical cancer

Updates of the current screening guidelines for the early detection of cervical cancer

Human papillomavirus DNA detection in women with normal and abnormal cervical Pap cytology

Cervical cancer is the second most common cancer in women worldwide and nearly all cases are human papillomavirus (HPV) related. Pap cytology screening has been very successful in lowering cervical cancer incidence and mortality in the US. With the increasing use of HPV DNA tests as a reflex test for ASC-US and co-testing of women over 30 for primary screening, there have been many reports of the HPV positive rates and clinical follow-up findings for women with various abnormal Pap diagnoses. This review describes the reported HPV detection rates for HSIL, LSIL, ASC-US, ASC-H, AGC, and negative Pap cytology and highlights the effect of HPV positivity on the follow-up detection of cervical lesions.

P16INK4a immunocytochemistry on cell blocks as an adjunct to cervical cytology: Potential reflex testing on specially prepared cell blocks from residual liquid-based cytology specimens

Background:p16 INK4a (p16) is a well-recognized surrogate molecular marker for human papilloma virus (HPV) related squamous dysplasia. Our hypothesis is that the invasive interventions and related morbidities could be avoided by objective stratification of positive cytologic interpretations by p16 immunostaining of cell block sections of cytology specimens.Materials and Methods:Nuclear immunoreactivity for p16 was evaluated in cell block sections in 133 adequate cases [20 negative for intraepithelial lesion or malignancy, 28 high-grade squamous intraepithelial lesion (HSIL), 50 low-grade squamous intraepithelial lesion (LSIL), 21 atypical squamous cells, cannot exclude HSIL (ASC-H), and 14 atypical squamous cells of undetermined significance (ASCUS)] and analyzed with cervical biopsy results.Results:(a) HSIL cytology (28): 21 (75%) were p16 positive (11 biopsies available — 92% were positive for cervical intraepithelial neoplasia (CIN) 1 and above) and 7 (25%) were p16 negative (3 biopsies available — all showed only HPV with small atypical parakeratotic cells). (b) LSIL cytology (50): 13 (26%) cases were p16 positive (12 biopsies available — all were CIN1 or above) and 37 (74%) were p16 negative (12 biopsies available — all negative for dysplasia. However, 9 (75%) of these biopsies showed HPV). (c) ASC-H cytology (21): 14 (67%) were p16 positive (6 biopsies available — 5 showed CIN 3/Carcinoma in situ/Ca and 1 showed CIN 1 with possibility of under-sampling. Cytomorphologic re-review favored HSIL) and 7 (33%) were p16 negative (5 biopsies available — 3 negative for dysplasia. Remaining 2 cases — 1 positive for CIN 3 and 1 showed CIN 1 with scant ASC-H cells on cytomorphologic re-review with possibility under-sampling in cytology specimen). (d) ASCUS cytology (14): All (100%) were p16 negative on cell block sections of cervical cytology specimen. HPV testing performed in last 6 months in 7 cases was positive in 3 (43%) cases.Conclusion:p16 immunostaining on cell block sections of cervical cytology specimens showed distinct correlation patterns with biopsy results. Reflex p16 immunostaining of cell blocks based on the algorithmic approach to be evaluated by a multiinstitutional comprehensive prospective study is proposed.