Xiang Tao

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

AbstractBackgroundA 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.MethodsIn 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.ResultsAmong 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.ConclusionsPapanicolaou 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.

Clinicopathological Characteristics and Prognosis of 91 Patients with Seromucinous and Mucinous Borderline Ovarian Tumors: a Comparative Study

To explore the differences in clinicopathological characteristics and prognosis between seromucinous borderline ovarian tumors (SMBOTs) and mucinous borderline ovarian tumors (MBOTs). Ninety-one patients with SMBOTs and MBOTs who underwent surgery at the Obstetrics and Gynecology Hospital of Fudan University from July 2006 to January 2015 were included. The median onset age of patients with SMBOTs (29 years, 20-77) was younger than that of patients with MBOTs (37 years, 16-71). SMBOTs were more likely to be exogenous and show bilateral ovarian involvement and had a smaller average tumor size of 10.63 cm, while MBOTs were more prone to endogenous growth and show unilateral involvement and had a larger average tumor size of 18.55 cm (p < 0.05). Compared with MBOTs, SMBOTs were characterized by the expression of Mullerian differentiation markers (p < 0.05). Recurrence occurred in 15.8% patients with SMBOT and 9.1% patients with MBOT. One case of SMBOT (2.6%) and one case of MBOT (2.3%) progressed to malignancy during follow-up, but no disease-related death was observed. Age less than 40 years was a risk factor for recurrence, while the effect of fertility-sparing surgery (FSS) on recurrence requires a larger sample size to be validated. The clinical characteristics of SMBOTs and MBOTs are similar but also quite different. High expression of Mullerian differentiation markers in SMBOT may indicate a better response to hormone therapy. Repeated FSS should be performed with caution and fully informed because of the risk of recurrence and progression to malignancy.

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

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

Risk stratification for cervical neoplasia using extended high‐risk HPV genotyping in women with ASC‐US cytology: A large retrospective study from China

BackgroundExtended high‐risk human papillomavirus (hrHPV) genotype testing (hrHPVGT) has emerged as a new strategy to help optimize the efficiency of hrHPV triage.MethodsWomen with an atypical squamous cells of undetermined significance (ASC‐US) cervical Papanicolaou test result who underwent hrHPVGT between October 2017 and May 2021 at the Obstetrics and Gynecology Hospital of Fudan University in Shanghai, China, were studied. For hrHPVGT, a proprietary multiplex real‐time polymerase chain reaction assay was used. hrHPVGT and viral load test results in selected patients were correlated with histopathologic follow‐up findings available within 6 months.ResultsIn total, 17,235 women with ASC‐US cytology who had hrHPVGT results were identified in the Obstetrics and Gynecology Hospital of Fudan University database. The hrHPV‐positive rate was 61.8%, and the most prevalent hrHPV genotypes were type 52 (HPV52) (16%), HPV16 (11.3%), HPV58 (10.2%), and HPV53 (8.4%). Single hrHPV genotypes were detected in 65.9% of women with hrHPV‐positive results, and multiple genotypes were detected in 34.1%. Histopathologic cervical findings within 6 months were available in 5627 hrHPV‐positive women and 2223 hrHPV‐negative women. High‐grade cervical intraepithelial lesions or cervical cancer (cervical intraepithelial neoplasia 2 or greater [CIN2+]) were identified in 7.5% of hrHPV‐positive women who had ASC‐US cytology and in 0.9% of hrHPV‐negative women who had ASC‐US cytology. The greatest risk for CIN2+ was in single hrHPV genotype infections with HPV16 (21.1%), HPV33 (15.2%), HPV82 (10%), and HPV18 (9.9%). hrHPVGT for genotypes HPV16, HPV33, HPV82, HPV18, HPV31, HPV45, HPV58, and HPV52 identified 95% of CIN2+ cases with 90.8% sensitivity, 53.8% specificity, a positive predictive value of 10.2%, and a negative predictive value of 99%. A significantly increased viral load was associated only with women who had HPV16‐related CIN2+.ConclusionshrHPVGT for women who have ASC‐US cytology allows for risk stratification capable of optimizing the efficiency of triage for hrHPV‐positive women.

Extensive HPV Genotyping Reveals High Association between Multiple Infections and Cervical Lesions in Chinese Women

Objective. The relationship between human papillomavirus (HPV) and cervical lesions has been extensively elucidated, but infection with multiple genotypes is less investigated due to methodology limitations. In the current study, with a method of genotyping 21 HPVs in a routine cervical screening population, we aimed to investigate the prevalence and diversity of HPV infections in Chinese women and further evaluate the impact of multiple infections of HPV on cervical lesion progression. Methods. Totally, 73,596 patients who underwent 21-genotype HPV testing from January 2018 to April 2019 were retrieved from the database of the Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University. HPV testing was performed by real-time PCR assay, including 13 high-risk HPVs (hrHPV), 5 potential hrHPVs, and 3 low-risk HPVs. Results. Of the 17,079 (infection rate, 23.2%) hrHPV- or potential hrHPV- (hr/phrHPV-) positive cases, 26.3% had multiple infections. Women younger than 25 and older than 65 were more prone to multiple infections. Of the hr/phrHPV-positive cases involving cervical intraepithelial neoplasia (CIN) 2 or worse (CIN2+), HPV73, 53, and 66 (=59) were the top three genotypes most likely to be included in multiple infections, while HPV16, 18, and 58 were the 3 least. Patients with single infection of HPV16 had higher incidences of CIN2+ than those with multiple-infection pattern ( P &lt; 0.001 ), indicating that mixing with other genotypes alleviated pathogenicity. The infection of HPV52, 53, 56, 51, 39, 66, 59, 68, and 35 showed an opposite pattern, indicating that they were less likely to be pathogens individually. All other types showed no significant differences, indicating the capability of pathogenesis independently. HPV26 showed a higher OR for CIN2+ than most traditional hrHPV genotypes. The vial load and the percentage of HPV16 showed positive correlation with the severity of cervical lesions. Conclusion. Extensive genotyping identified 3 most frequent genotypes, HPV16, 52, and 58, in CIN2+ of Chinese population. HPV16 mixing with other genotypes alleviated its pathogenicity. The vial load and the percentage of HPV16 were positively correlated with the severity of cervical lesions. HPV26 may be considered as a hrHPV, which needs to be evaluated and confirmed by more cases.

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

BACKGROUNDThe 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.METHODSWomen 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.RESULTSIn 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.CONCLUSIONSThis large retrospective study in a predominantly unvaccinated cohort demonstrated that extended hrHPV genotyping improves genotype‐specific risk stratification in women with L‐SIL.;

Scrutinizing high‐risk patients from ASC‐US cytology via a deep learning model

BACKGROUNDAtypical squamous cells of undetermined significance (ASC‐US) is the most frequent but ambiguous abnormal Papanicolaou (Pap) interpretation and is generally triaged by high‐risk human papillomavirus (hrHPV) testing before colposcopy. This study aimed to evaluate the performance of an artificial intelligence (AI)‐based triage system to predict ASC‐US cytology for cervical intraepithelial neoplasia 2+ lesions (CIN2+).METHODSMore than 60,000 images were used to train this proposed deep learning‐based ASC‐US triage system, where both cell‐level and slide‐level information were extracted. In total, 1967 consecutive ASC‐US Paps from 2017 to 2019 were included in this study. Histological follow‐ups were retrieved to compare the triage performance between the AI system and hrHPV in 622 patients with simultaneous hrHPV testing.RESULTSIn the triage of women with ASC‐US cytology for CIN2+, our system attained equivalent sensitivity (92.9%; 95% confidence interval [CI], 75.0%‐98.8%) and higher specificity (49.7%; 95% CI, 45.6%‐53.8%) than hrHPV testing (sensitivity: 89.3%; 95% CI, 70.6%‐97.2%; specificity: 34.3%; 95% CI, 30.6%‐38.3%) without requiring additional patient examination or testing. Additionally, the independence of this system from hrHPV testing (κ = 0.138) indicated that these 2 different methods could be used to triage ASC‐US as an alternative way.CONCLUSIONThis de novo deep learning‐based system can triage ASC‐US cytology for CIN2+ with a performance superior to hrHPV testing and without incurring additional expenses.;