Low-grade Squamous Intraepithelial Lesion Cytology Research Articles

PAP-test: Possibilities and Limitations

Cervical cancer (CC) progresses slowly, and the cytological screening increases the likelihood of early detection of precancerous lesions. Cytology of the cervix is one of the primary methods of effective CC diagnosis, which, thanks to early detection and timely treatment, leads to a stable decrease in morbidity and mortality from invasive CC. The results of many studies have shown that the specificity of the conventional Pap smear test is approximately 80–100%, its sensitivity ranges from 30% to 80%, and the rate of inadequacy of this method is from 5% to 25%. With traditional smear preparation, only a small percentage of collected cells end up on the slide, while abnormal cells may be discarded and not analyzed. When viewing the slide, cells that have dried and clumped together may interfere with the visualization of atypical cells. To overcome these limitations, in 1996, as an alternative to the traditional Pap test, liquid cytology was presented – the technology of preparing slides on which the cells are placed in a single layer. This technology outperformed the conventional Pap test with improved fixation, reduced obscuring factors, and standardized cell transfer. In liquid cytology samples are collected by fully immersing the cytobrush in a vial containing a preservative liquid, whereby the cells are preserved and fixed simultaneously, unlike conventional smears where the sample is applied to a glass slide and fixed separately. Today, two main methods of preparation based on liquid cytology are known: ThinPrep and SurePath. The results of cytology are described according to the Bethesda system. The Bethesda classification is widely accepted because it corresponds to the clinical presentation, reproduces the nature of the lesions, and is therefore treatmentoriented with a desirable follow-up procedure. The indisputable advantage of the Pap test by liquid cytology is the ability to perform both cytological and molecular studies, in particular HPV, in one sample. This capability facilitated the implementation of a two-step strategy when HPV testing is used as a triage test for ASC-US or low-grade squamous intraepithelial lesion cytology, or when cytology is used to triage HPV-positive women.

Underestimated Cervical Cancer among Women over 65 Years Old: Is It Time to Revise the Screening Target Age Group?

To compare cytological and histological results from women > 64 years old who followed the Brazilian national cervical cancer screening guidelines with those who did not. The present observational retrospective study analyzed 207 abnormal cervical smear results from women > 64 years old in a mid-sized city in Brazil over 14 years. All results were reported according to the Bethesda System. The women were divided into those who followed the screening guidelines and those who did not. Atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion cytology results were found in 128 (62.2%) cases. Of these, 112 (87.5%) had repeated cytology with positive results. The other 79 (38.1%) with abnormal results should have been referred to colposcopy and biopsy. Out of 41 (51.9%) biopsied women, 23 (29.1%) had a confirmed diagnosis of neoplasia or precursor lesion. In contrast, among the 78 (37.7%) biopsied patients, 40 (51.3%) followed the guideline recommendations, with 9 (22.5%) positive biopsies. Of the 38 (48.7%) women who did not follow the guidelines, there were 24 (63.1%) positive results. Women who did not follow the guidelines demonstrated higher chances of cancer and precursor lesions (odds ratio [OR]: 5.904; 95% confidence interval [CI]: 2.188-15.932; p = 0.0002). Women > 64 years old who did not follow the national screening protocol showed significant differences in the frequency of abnormal results and severity of diagnosis compared with those who followed the protocol.

Correlation of immediate prevalence of cervical squamous cell precancers and cancers with HPV genotype and age in women with LSIL cytology: A retrospective analysis of 1617 cases.

To evaluate the immediate risk of cervical squamous cell precancers and cancers in women with low-grade squamous intraepithelial lesion (LSIL) cytology according to different high-risk human papillomavirus (hrHPV) results and age stratification. The study included 1617 women with LSIL cytology and underwent simultaneous Aptima HPV genotyping (E6/E7 mRNA test) followed by cervical biopsy. Among 1317 hrHPV positive cases, other 11 types of hrHPV were the most frequent (68.8%), followed by HPV16 (11.1%), HPV18/45 (4.1%), and HPV16/HPV18/45 (0.5%). Compared to other groups, HPV18/45 positive group and other 11 types of hrHPV group showed significantly higher prevalence of intraepithelial neoplasia grade (CIN)1 (p < .0001), while HPV16 positive and HPV16/HPV18/45 dual positive groups showed significantly higher prevalence of CIN2/3 (p < .0001). In addition, hrHPV positive, 25-39 years-old age group showed a significantly higher prevalence of CIN1 (p = .032) than the other age groups. Furthermore, CIN1 prevalence was significantly higher in patients under 40 or 50 years of age than in those over 40 or 50 years of age (p = .005 and p = .011, respectively). However, there was no significant difference among the different age groups in CIN2/3 prevalence in women with LSIL cytology. In southern Chinese women population, LSIL cytology carries very low immediate risk of high-grade squamous intraepithelial lesions (HSIL) (CIN2/3) in general. However, HPV16 positive and HPV16/HPV18/45 dual positive indicated a higher immediate risk of high-grade squamous intraepithelial lesions (HSIL) (CIN2/3). Age is not an immediate risk factor in this patient population for high-grade squamous lesions or SCC. These results are similar to data from cytology laboratories in the United States and other international settings, therefore strongly support the usage of ASCCP guidelines in this patient population.

Efficacy of optical coherence tomography in the triage of women with minor abnormal cervical cytology before colposcopy.

To evaluate the efficacy of Optical Coherence Tomography (OCT) for detecting cervical lesions in women with minor abnormal cytology results (atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL)). A prospective study was conducted at gynecologic clinic from Mar 2021 to Sep 2021. The recruited women with cervical cytological findings of ASC-US or LSIL were inspected with OCT before colposcopy-directed cervical biopsy. The diagnostic performance of OCT, alone and in combination with high-risk human papillomavirus (hrHPV) testing were evaluated to detect cervical intraepithelial neoplasia of grade 2 or worse (CIN2+)/CIN3 or worse (CIN3+). The rate of colposcopy referral and the immediate risk of CIN3+ of OCT were calculated. A total of 349 women with minor abnormal cervical cytology results were enrolled. For detection of CIN2+/CIN3+, the sensitivity and NPV of OCT were lower than those of hrHPV testing (CIN2+: 71.3% vs. 95.4%, 89.0% vs. 91.1%, P < 0.001; CIN3+: 75% vs. 93.8%, 96.5% vs. 95.6%, P < 0.001), but the specificity, accuracy and PPV were higher than those of hrHPV testing (CIN2+: 77.5% vs. 15.6%, 75.9% vs. 35.5%, 51.2% vs. 27.3%, P < 0.001; CIN3+: 69.4% vs. 13.6%, 69.9% vs. 20.9%, 19.8% vs. 9.9%, P < 0.001). OCT combined with hrHPV testing (CIN2+: 80.9%; CIN3+: 72.6%) showed higher specificity than that of OCT alone (P < 0.001). The colposcopy referral rate base on OCT classification was lower than that based on hrHPV testing (34.7% vs. 87.1%, P < 0.001). Patients with hrHPV-positive ASC-US and hrHPV-negative LSIL cytology, the immediate CIN3+ risk in OCT negative cases was less than 4%. OCT alone or combination with hrHPV testing shows good performance for detecting CIN2+/CIN3+ in patients with ASC-US/LSIL cytology. OCT is an effective method for colposcopy triage in women with hrHPV-positive ASC-US and hrHPV-negative LSIL cytology.

HPV Pozitif Kadınlarda ASC-US ve LSIL Sitolojilerinin Klinik Veri ve Kolposkopi Sonuçlarının Karşılaştırılması

ABSTRACT&#x0D; Objective: The aim of our study is to compare the clinical data and colposcopy- directed biopsy (CDB) results of atypical squamous cell of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) cytology among high risk human papilloma virus (hrHPV) positive women.&#x0D; Materials and Methods: A total of 359 hrHPV-positive patients with ASC-US and LSIL cytology, between 20-67 years of age were included in the study. Participants’ age, education status, smoking status, colposcopy results, and number of CDBs were assessed and clinical data compared with histopathologic evaluation of biopsies statistically. &#x0D; Results: There were no statistically significant differences in terms of age, marital status, education status and smoking status of hrHPV + ASC-US and hrHPV + LSIL groups. Both groups were compared in terms of histopathologic results of CDBs and no statistically significant difference was observed between the groups. The number of CDB material and frequency of endocervical curettage were significantly higher in hrHPV + LSIL than hrHPV + ASC-US patients. There was no statistically significant difference between the two groups in terms of advanced treatment need. Control cytology performed during follow-up of both ASC-US and LSIL groups were resulted as benign.&#x0D; Conclusion: The approach to ASCUS and LSIL is similarly important in HPV positivity. Since our follow up period includes a sort period of 1 year, further studies need to be carried out in order to demonstrate longer term outcomes.

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.

Human papillomavirus genotype distribution in low-grade squamous intraepithelial lesion cytology, and its immediate risk for high-grade cervical lesion or cancer: a single-center, cross-sectional study

ObjectiveTo investigate the distribution of human papillomavirus (HPV) genotypes in low-grade squamous intraepithelial lesion (LSIL) cytology and the immediate risk of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) lesions.MethodsThis prospective cross-sectional study enrolled women aged ≥21 years that were diagnosed with LSIL cytology at Siriraj Hospital (Bangkok, Thailand) during 2017–2019. Anyplex II HPV testing was performed to detect 14 high-risk HPV cases prior to colposcopy-directed biopsy.ResultsIn total, 318 patients were included in the final analysis. Of those, 24 (7.5%), 241 (75.8%), 53 (16.7%) were aged 21–25 years, 25–50 years, and ≥50 years, respectively. Eighty-two patients (25.8%) had abnormal screening results within the previous 5 years. High-risk HPV infection was found in 188 patients (59.1%) with 127 (39.9%) having single and 61 (19.2%) having multiple infections. The five most common HPV genotypes were HPV 66 (18.6%), HPV51 (9.7%), HPV58 (9.4%), HPV16 (9.1%), and HPV56 (8.2%). The immediate risk of CIN2+ was 6% in LSIL, regardless of the HPV status, 8% in high-risk HPV-positive LSIL, and 3.1% in high-risk HPV-negative LSIL. When using 6% as the threshold risk for colposcopy, performing reflex HPV testing in LSIL cytology can decrease the number of colposcopies by 40.9%, with an area under the receiver operating characteristic curve of 0.6 (95% confidence interval, 0.5–0.7).ConclusionThe study findings support the idea that geographic variations affect the HPV genotype. Reflex HPV testing may decrease the number of colposcopies in cytology-based screening regions with a high prevalence of low-carcinogenic HPV.

The clinical utility of extended high-risk HPV genotyping in risk-stratifying women with L-SIL cytology: A retrospective study of 8726 cases.

The value of extended high-risk human papillomavirus (hrHPV) genotyping for cervical cancer screening in women with low-grade squamous intraepithelial lesion (L-SIL) cytology has been recognized, but few studies have investigated this. Women with L-SIL Papanicolaou results who underwent human papillomavirus (HPV) genotyping between October 2017 and October 2021 at the Obstetrics and Gynecology Hospital of Fudan University were identified. Their HPV results were correlated with immediate histopathologic follow-up findings. In total, 8726 women who had L-SIL cytology and extended HPV genotyping results were analyzed. The overall hrHPV-positive rate was 84% in women with L-SIL, and the most prevalent hrHPV genotypes were type 52 (HPV52) (20.7%), HPV53 (15.7%), and HPV16 (14.3%). Single and multiple coinfections of hrHPV genotypes were detected in 57.2% and 42.8% of women with positive hrHPV results, respectively. Cervical intraepithelial neoplasia grade ≥2 (CIN2+) was identified in 8.5% of hrHPV-positive women. The CIN2+ detection rate in women who had multiple hrHPV infections (9.9%) was significantly higher than the rate in those who had infection with a single HPV type (7.2%). The top 5 CIN2+-associated HPV infections were HPV16 (25.2%), HPV82 (17.8%), HPV33 (16.3%), HPV31 (14.6%), and HPV26 (13.8%). For the composite group with HPV types HPV16, HPV26, HPV82, HPV31, HPV18, HPV33, HPV58, HPV35, HPV52, and HPV51, the risk of CIN2+ was 11.5% and represented 97.1% of all CIN2+ in biopsied, hrHPV-positive patients. The composite group of 8 remaining HPV genotypes (HPV39, HPV45, HPV53, HPV56, HPV59, HPV66, HPV68, and HPV73) was identified in 29.7% of hrHPV-positive patients, and the risk of CIN2+ for this composite group was similar to the risk of CIN2+ in hrHPV-negative patients. This large retrospective study in a predominantly unvaccinated cohort demonstrated that extended hrHPV genotyping improves genotype-specific risk stratification in women with L-SIL.

HIV-Infected Women with Low-Grade Squamous Intraepithelial Lesion on Cervical Cytology Have Higher Risk of Underlying High-Grade Cervical Intraepithelial Neoplasia.

Objective: To evaluate the risk of histological high-grade cervical lesions defined as cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in women with human immunodeficiency virus (HIV) infection who had low-grade squamous intraepithelial lesions (LSIL) on cervical cytological screening compared with HIV-uninfected women who had similar cytology. Methods: 127 HIV-positive women aged 18–65 years with LSIL cytology undergoing colposcopic examination between January 2008 and December 2019 at Chiang Mai University Hospital were reviewed. By matching 1:1 ratio for age (±5 years) and examination time period (±12 months), 127 HIV-negative women with LSIL cytology in the same period were recruited as controlled subjects for comparison. The patients’ characteristics, HIV status, CD4 counts, antiretroviral therapy, and histopathology on cervical biopsy were analyzed. Results: HIV-infected women significantly had early sexual debut (age < 20 years) and more sexual partners (≥2) than HIV-uninfected women. The risk of underlying CIN2+ in HIV-infected women was significantly higher than that in HIV-negative women (20.5% vs. 9.4%, p = 0.021) with an odds ratio (OR) of 2.47 and 95% confidence interval (CI) = 1.18–5.14. After adjustment, the risk of underlying CIN2+ in HIV-infected women remained significantly higher than that in HIV-uninfected women (adjusted OR = 2.55, 95% CI = 1.11–5.82, p = 0.027). Conclusion: Among women with LSIL on cervical cytology, the risk of underlying CIN2+ in HIV-infected women was approximately 2.5 times higher than those without HIV infection. Colposcopy is indicated particularly in the case of women with a long duration of HIV infection.

Prevalence of High-grade Cervical Lesion (CIN 2+) in Women with Low Grade Squamous Intraepithelial Lesion Cytology

Background: The frequency of high-grade cervical intraepithelial neoplasia (CIN2+) among Thai women with abnormal cytology, including low-grade squamous intraepithelial lesion (LSIL), was previously reported as higher than in Western populations. The aim of this study was to evaluate the prevalence of underlying significant cervical lesions (CIN2+) in women with LSIL cytology. Materials and Methods: A cross-sectional study was conducted among Thai women who participated in a screening program at the women&rsquo;s health clinic at Chulabhorn Hospital, Thailand, between July 2011 and August 2013. A total of 63 women with LSIL cytology were recruited for colposcopic evaluations. Results: A total of 63 women with LSIL smear were included; the median age was 38 years (22 to 67 years). Most women were multiparous (61.9%) and premenopausal (80.9%). After colposcopic evaluations, the histological results were as follows: 7 (11.1%) cases with CIN2, CIN3 or adenocarcinoma in situ; 18 (28.6%) with CIN1; 32 (66.7%) with no epithelial lesion; and no cases with cervical cancer. No clinical factors were found to correlate with high-grade cervical lesions. Conclusion: The rates of high-grade cervical lesion (CIN2+) at initial colposcopy following LSIL cytology in our population were lower than reported in previous studies. Keywords: Prevalence, Cervical intraepithelial neoplasia (CIN), Low-grade squamous intraepithelial lesion (LSIL), Thailand

ASCCP Risk-Based Colposcopy Recommendations Applied in Thai Women With Atypical Squamous Cells of Undetermined Significance or Low-Grade Squamous Intraepithelial Lesion Cytology.

To compare the proportion of cervical intraepithelial neoplasia (CIN) 2 or worse pathology among different risk strata according to the ASCCP when applied in women who had atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesion (LSIL) cervical cytology; to assess performance of colposcopy; and to assess the independent predictors for detected CIN 2 or worse pathology. This is a secondary analysis of a previous prospective study, which included Thai women with ASC-US or LSIL cytology who underwent high-risk human papillomavirus (HPV) testing and subsequent colposcopy with directed biopsy. Patients were classified as lowest-risk, intermediate-risk, or highest-risk based on cervical cytology, high-risk HPV testing, and colposcopic impression. The proportion of CIN 2 or worse pathology and associated prognostic factors were analyzed. Of 697 women, 103 (14.8%), 573 (82.2%) and 21 (3%) were classified into lowest-risk, intermediate-risk, and highest-risk groups, respectively. The proportion of CIN 2 or worse pathology was 1%, 11.2%, and 61.9% in those same groups, respectively (P<.001). Colposcopy to detect CIN 2 or worse pathology had a sensitivity, specificity, positive predictive value, and negative predictive value of 98.7%, 18%, 13.2%, and 99.1%, respectively. Independent predictors for detecting CIN 2 or worse pathology were positive high-risk HPV, HPV 16/18 positivity, and high-grade colposcopic impression. This study supports a no biopsy with follow-up strategy in the lowest-risk group, inconsistent with ASCCP recommendations, but is in alignment with a strategy of multiple targeted biopsies in the intermediate-risk and highest-risk groups.

Cytological Follow-Up of Cervical Intraepithelial Neoplasia 1 after Initial Management During 2-Year Period: Bhumibol Adulyadej Hospital Experience

Objective: To evaluate the frequency of cervical cytological results in patients diagnosed as low-grade squamous intraepithelial lesion (LSIL) in cytology report between women younger than 30 and woman 30 or older after initial management and the completed 2-year follow-up to suggest the proper management for Thai women. Materials and Methods: The present study was retrospectively conducted at Bhumibol Adulyadej Hospital, Bangkok, Thailand between January 2011 and December 2016. The medical records of 279 patients whose cervical cytology reported LSIL were reviewed. The prevalence of silent high grade cervical intraepithelial neoplasia (CIN 2/3) in LSIL cytology result was determined. The results of the cervical cytology after the patients completed the 2-year follow-up were evaluated. Results: During the present study period, 279 cases of LSIL in cytology result were enrolled. In women with LSIL in the cytology report, two-third were in pre-menopausal status. The prevalence of CIN 2/3 in LSIL cytology in women younger than 30 and 30 or older were 11.9% and 11.2%, respectively. At 2-year follow-up, around 97% of the patients who completed the follow-up had a spontaneous regression of the disease in both aged groups. Three percent of cases (3/85) had persistent disease in women 30 or older only. There was no progressive disease in the present study. Conclusion: Silent CIN 2/3 in LSIL cytology in the present study were high. Colposcopy should be recommended for diagnosis and follow-up in this setting. Abnormal Pap at 2-year follow-up was around three percent, therefore, abnormal cytology was still a problem. Continuous close cytology follow-up is still recommended. Keywords: Low-grade squamous intraepithelial lesion, LSIL, Cervical intraepithelial neoplasia, CIN, Cytology

Value of multi-quadrants biopsy: Pooled analysis of 11 population-based cervical cancer screening studies.

ObjectiveThe accuracy of colposcopy-guided biopsy is key to the success of colposcopic triage in cervical cancer screening programs. However, there is no widely adopted biopsy guideline up to date. Our study aimed to determine whether multi-quadrants biopsy improves the yield of cervical lesions.MethodsEleven population-based cervical cancer screening studies were conducted in China. Cytology, high-risk human papillomavirus (hrHPV) testing and visual inspection were performed for primary screening. Females positive on one or more tests were referred for colposcopy and biopsy. The proportion of detected cervical intraepithelial neoplasia (CIN)2+ and yields by quadrant lesion-targeted biopsy or 4-quadrant random biopsy were compared.ResultsAmong 4,923 females included, 1,606 had quadrant lesion-targeted biopsy, and 3,317 had 4-quadrant random biopsy. The cumulative CIN2+ yield increased from 0.10 for only one quadrant-targeted biopsy to 0.21, 0.34, and 0.58 for at most two, three and four quadrants targeted biopsies. Among hrHPV positive females with high-grade squamous intraepithelial lesion (HSIL)+ cytology, the cumulative CIN2+ yield of a second targeted biopsy in another quadrant was significantly increased (P<0.05). Among hrHPV-negative females, the yield of 4-quadrant random biopsies was 0.005, and the yield by lesion-targeted biopsies was 0.017. For hrHPV positive females who had 4-quadrant random biopsy, the additional CIN2+ yield for HSIL+, low-grade squamous intraepithelial lesion (LSIL) cytology, or abnormal visual inspection via acetic acid and Lugol’s iodine (VIA/VILI) were 0.46, 0.11, 0.14.ConclusionsA 4-quadrant random biopsy is recommended only for hrHPV positive females with HSIL cytology, and is acceptable if hrHPV positive with LSIL cytology or with abnormal VIA/VILI. Our findings add evidences for an objective and practical biopsy standard to guide colposcopy in cervical cancer screening programs in low- and middle-income countries.

Risk detection for high-grade cervical disease using Onclarity HPV extended genotyping in women, ≥21 years of age, with ASC-US or LSIL cytology

ObjectivesThere is growing interest in using human papillomavirus (HPV) genotyping as a risk-based triage approach for women with atypical squamous cells-undetermined significance (ASC-US) and low-grade squamous intraepithelial lesions (LSIL) cytology. MethodsThis analysis includes 2807 subjects with ASC-US or LSIL cytology, ≥21 years, from the baseline phase of the Onclarity HPV trial. All women were referred to colposcopy/biopsy. Hierarchical-ranked prevalence and risk values, associated with high-grade cervical disease, were calculated based on extended genotyping. ResultsHPV 16 carried the highest risk for cervical intraepithelial neoplasia grade 2 or worse (≥CIN2) in both the ASC-US and LSIL populations. Risk of ≥CIN3 and ≥CIN2 associated with the other 13 genotypes varied somewhat for women with ASC-US and LSIL, however, HPV 31, 18, 33/58, 51 and 52 appear to comprise an intermediate risk band. Risk associated with HPV 35/39/68, 45, and 56/59/66, in either cytology population, was relatively low and beneath the benchmark threshold risk for immediate colposcopy. Restricting the analysis to women 21–24 years, ≥25 years, or ≥30 years produced similar results. ConclusionsHPV genotyping identified multiple risk bands for ≥CIN3 and ≥CIN2 in the ≥21 year-old ASC-US and LSIL populations. These results support a 1-year follow-up period to preclude immediate colposcopy for ASC-US or LSIL women positive for the lowest-risk HPV genotypes.

Follow-up with histopathology and HPV testing on LSIL cytology in China's largest academic woman's hospital.

Cervical cancer remains a major health problem in China. To provide baseline data for establishing the appropriate screening strategy, the authors investigated the histopathologic follow-up and human papillomavirus (HPV) testing results of low-grade squamous intraepithelial lesion (LSIL) cytology in the Chinese Largest Women Hospital. Women with LSIL cytology, human papillomavirus (HPV) testing, and immediate histopathologic follow-up between 2011 and 2016 were analyzed. The frequency of LSIL among 1,095,022 Papanicolaou (Pap) tests was 1.4%, and was significantly higher in cases using liquid-based cytology (LBC; 1.5%-1.6%) compared with conventional Pap smears (CPS; 0.5%). The CPS method had performance for predicting cervical intraepithelial neoplasia (CIN) that was comparable to that of LBC (75% vs 69.1% and 71.9%). Among 8079 LSIL cases with an immediate histopathologic diagnosis, CIN-2/3 or higher (CIN-2/3+) was found in 11.9% of cases and carcinoma in 0.3% of cases. A total of 158 patients (15.7%) with HPV-positive LSIL had a diagnosis of CIN-2/3 compared with 18 patients (5.5%) with HPV-negative LSIL. In postmenopausal women with LSIL cytology, the detection rate for CIN-2/3 in HPV-negative patients was significant lower than that in HPV-positive patients. Furthermore, HPV type 16 (HPV-16) was the most common genotype noted in patients with CIN-2+ lesions, whereas HPV-18 was the most common in patients with CIN-1. Although its reporting rate is lower than that of LBC, CPS is useful due to its low cost and comparable predictive value. HPV testing is helpful for stratifying postmenopausal women with LSIL into lower and higher risk groups. HPV-16 is the most commonly identified genotype in CIN-2+ lesions diagnosed in Chinese women with LSIL cytology, whereas HPV-18 is the most commonly identified genotype in patients with CIN-1 lesions.

Post-colposcopy Management of ASC-US and LSIL Pap Tests (PALS Trial): Pilot RCT.

Evidence supporting optimal follow-up of women with atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesion cytology found to have low-grade disease or normal findings at initial colposcopy is weak. Surveillance options include continued colposcopy, discharge with Pap testing, or HPV testing at 12 months. This study was a pilot RCT comparing these three follow-up policies. The objectives were to determine the feasibility of an RCT and to compare the incidence of greater than or equal to high-grade squamous intraepithelial lesion (≥HSIL) in each of the follow-up policies. A total of 133 women referred with ASC-US or low-grade squamous intraepithelial lesion cytology between June and August 2012 underwent initial colposcopy where incident ≥HSIL histology was ruled out. Of these women, 125 were randomly assigned to colposcopic surveillance, Pap testing, or HPV testing. Patients with high-risk results at any point were treated according to standard of care. Patient recruitment and adherence to follow-up were calculated using descriptive statistics. Accuracy of the three follow-up arms was calculated (Canadian Task Force Classification: IC). Recruitment rates were 80%, and adherence to protocol was 85% to 100%. Nine of 125 (7.2%) patients overall were found to have ≥HSIL histology at exit: one of 43 in the reference colposcopy group, and six of 41 and three of 41 in Pap and HPV arms, respectively. One early cancer was detected in the HPV arm. Sensitivity and specificity (CI) for each arm, respectively, were as follows: colposcopy N/A, 100% (88.1%-100%); Pap, 100% (47.8%-100%) and 85.7% (63.7%-97%); and HPV, 66.7% (9.4%-99.2%) and 68% (46.5%-85.1%). This pilot study demonstrated the operational and safety feasibility of an RCT in this patient population. Validation of clinical findings is necessary.

Potential influence of p16 immunohistochemical staining on the diagnosis of squamous cell lesions in cervical biopsy specimens: observation from cytologic-histologic correlation.

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

Immediate histopathologic follow-up of cervista and aptima high-risk HPV assays in women with LSIL cytology.

Recent guidelines recommended the optional deferral of colposcopy for postmenopausal women with low-grade squamous intraepithelial lesion (LSIL) Papanicolaou (Pap) test results and negative human papillomavirus (HPV) testing. The objective of the current study was to assess the histopathologic follow-up of Cervista and Aptima high-risk HPV (hrHPV) testing in patients with LSIL cytology. Women with LSIL Pap test results and Cervista or Aptima hrHPV testing results were retrospectively identified from June 2013 through July 2017. Histological follow-up results within 6 months after LSIL Pap tests were analyzed. A total of 1731 and 1906 cases of LSIL Pap tests, respectively, were tested on Cervista and Aptima platforms. Among the 2119 cases with histopathologic follow-up, cervical intraepithelial neoplasia of types 2/3 (CIN2/3) was diagnosed in 184 women (8.9%) and the detection rate was significantly higher in women with positive HPV testing compared with those with a negative result on both assays. Both methods demonstrated comparable performance for detecting CIN2/3 lesions. However, in women aged ≥50 years, the specificity for the detection of CIN2/3 lesions by the Aptima assay was statistically significantly higher than that of the Cervista test (48.7% vs 23.1%; P<.01), although there were no significant differences in the sensitivity, positive predictive value, and negative predictive value between these 2 assays in this age group. The Aptima assay was found to be statistically significantly more specific than the Cervista test for detecting CIN2/3 lesions among women aged ≥50 years. These findings not only further support the recommendations by the American Society for Colposcopy and Cervical Pathology that hrHPV triage is an acceptable option for postmenopausal women with LSIL cytology, but also provide additional evidence that HPV RNA testing may be more useful in clinical risk stratification due to its specificity in the postmenopausal population. Cancer Cytopathol 2018. © 2018 American Cancer Society.

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.

The Prevalence of Genus Alpha Human Papillomavirus in Women with Uterine Cervical Infection and/or Inflammation in Western Iran

Introduction:Human papillomavirus (HPV) infection is strongly associated with risk of cervical cancer and genital warts.Aim:The study aimed to report the prevalence of genus alpha human papillomavirus (HPV) types in women with cervical infection and/or inflammatory in Western Iran.Materials and Methods:In a cross-sectional study, 435 women were clinically diagnosed with cervical infections. The method of HPVs detection was polymerase chain reaction (PCR). The majority of patients (304 patients) did Pap smear based on liquid-based specimens.Results:Out of 435 patients, 150 patients (34.5%) had HPV positivity that the prevalence of high-risk HPVs was 52.7%. Out of 76 patients with Pap smear positivity, 68.4% had atypical squamous cells of undetermined significance cytology class and 31.6% had low-grade squamous intraepithelial lesion cytology class. The most prevalence rate of HPV was in age ≤30 years. HPV 16 and HPV 56 were the most prevalence rate among high-risk HPVs. Overall HPV alpha-10 (59%) and HPV alpha-9 (32.2%) had the most prevalence rate.Conclusions:Among high-risk HPVs, HPV 16 was the most common HPV detected in our population with a very low prevalence of HPV 18. In addition, HPV 6 and then HPV 11 had the most prevalence rate in the women with uterine cervix (cervical) infection among low-risk HPVs.