Chengquan Zhao

Assessment of the efficiency and accuracy of an artificial intelligence assistive system in the diagnosis of Pap cervical atypical glandular cell cytology

Abstract Background A diagnosis of atypical glandular cells (AGC) on Papanicolaou (Pap) slides is rare but has clinically significant findings associated with high‐risk cervical and endometrial lesions. The authors evaluated the efficiency and diagnostic performance of an artificial intelligence (AI)‐assisted platform (Riuqian WSI‐2400; with the registered trademark AICyte) in identifying AGCs on Pap slides. Methods A retrospective analysis of 485 Pap cases was conducted, including 185 cases with AGCs, 50 cases with high‐grade squamous intraepithelial lesions, 50 cases with low‐grade squamous intraepithelial lesions, and 200 negative cases; of these, 264 cases had histologic correlations. An experienced cytopathologist reviewed all slides using conventional microscopy and AICyte. Then, the same cases were evaluated by two other pathologists using the AICyte system. Results The initial study demonstrated a kappa value of 0.744, which indicated strong agreement of the Pap interpretation from the same pathologist between using microscopy and AICyte methods, whereas the average interpretation time was significantly reduced with AICyte (137 vs. 44 seconds). Diagnostic consensus among three pathologists using the AICyte system was strong, with a Kendall W coefficient of 0.802. The AICyte‐pathologist consensus reached an exact match with original interpretations in 95.1% of cases. AICyte‐assisted interpretations demonstrated improved specificity and diagnostic accuracy for glandular lesions compared with original interpretations while maintaining 100% sensitivity and negative predictive value. Conclusions To the authors' knowledge, this is the first study focusing on assessment of AGCs on an artificial intelligence system. The findings demonstrated that the AICyte system offers substantial improvements in efficiency and diagnostic consistency for the interpretation of AGCs and significantly reduces slide reading time. These results support the potential of AI to augment performance, especially in resource‐limited settings or high‐volume screening environments.

Assessment of microorganism detection in ThinPrep Papanicolaou tests utilizing the Hologic Genius Digital Diagnostics System

Abstract Objective The Hologic Genius Digital Diagnostics System (HGDDS) analyzes ThinPrep Papanicolaou (Pap) tests (TPPTs) to assist in detecting cervical lesions. The aim of this study was to determine the sensitivity of the HGDDS in identifying commonly diagnosed microorganisms in Pap tests. Methods A total of 305 TPPT cases were selected from Magee Women’s Hospital, University of Pittsburgh, consisting of 244 cases with microorganism diagnoses (a total of 262 cases of Actinomyces, Candida spp, herpes simplex virus [HSV], and Trichomonas) and 61 cases without microorganisms. Slides were scanned and then subjected to artificial intelligence (AI) analysis using the HGDDS and subsequently reviewed on a digital workstation by a cytologist, followed by a resident and a cytopathologist who made the final diagnoses. Results Diagnosis using the HGDDS demonstrated high sensitivity across all microorganisms (95.4%). Herpes simplex virus detection was comparatively lower (82.5%). Of the microorganisms, 85.2% were displayed in the first gallery of 30 images within row 5, 7.2% presented in the first gallery outside of row 5, and 7.6% presented in the hidden gallery of images. Among the 12 cases with missed diagnoses, 3 of 5 Candida spp and 3 of 7 HSV organisms were not presented within the 60 images selected by HGDDS. In another 6 cases, microorganisms were found within the 60 fields, but none were present in row 5. Conclusions Very high sensitivity was observed for TPPTs across 3 of 4 common microorganisms on the HGDDS, although sensitivity was relatively lower for detecting HSV. Understanding morphologic patterns of various microorganisms in detection misses by the HGDDS may help guide the implementation of AI-assisted cervical cancer screening systems.

Assessment of reprocessed ThinPrep cytology cases after glacial acetic acid wash procedure using the Hologic Genius Digital Diagnostics System

This study focuses on ThinPrep Pap tests with a low to borderline number of cells and the performance of AI-assisted digital systems in cases that have undergone the acetic acid wash procedure (AAW). Four hundred sixty-two cases initially interpreted as unsatisfactory and finally interpreted as satisfactory after AAW procedure were included in the study. These ThinPrep Pap slides were scanned using the Genius Digital Diagnostic System (GDDS). Overall agreement between GDDS and Original ThinPrep Interpretation (OTPI) was 63.2% for diagnostic match (Negative for Intraepithelial Lesion, ASCUS, Low Grade Squamous Intraepithelial Lesion, Atypical Squamous Cells, High Grade, Atypical Glandular Cells, or unsatisfactory), and 66.0% when ASCUS + diagnoses are grouped. Out of the 462 cases, 364 (78.8%) were called Negative for Intraepithelial Lesion based upon the manual OTPI, as opposed to 310 (67.1%) reviewed using the GDDS. There were 17.5%, 1.3%, 0.9% and 1.5% cases called Atypical Squamous Cells of Undetermined Significance, Low Grade Squamous Intraepithelial Lesion, Atypical Squamous Cells, High Grade Cannot be Excluded, and Atypical Glandular Cells respectively on OTPI, as opposed to 24.7%, 3.0%, 0.6% and 1.5% respectively by the GDDS. Only 3.0% of the cases were deemed unsatisfactory by GDDS. All the cases with high grade results in the subsequent cervical biopsy were diagnosed as at least Atypical Squamous Cells of Undetermined Significance and above by the GDDS. The diagnostic agreement between GDDS and biopsy was 65.2% compared to 58.7% for OTPI, although this is not statistically significantly different, (χ Our results demonstrate that the GDDS can be successfully used to screen ThinPrep Pap Tests that have undergone the AAW procedure.

Assessment of the efficacy and accuracy of cervical cytology screening with the Hologic Genius Digital Diagnostics System

Abstract Background Medical technologies powered by artificial intelligence are quickly transforming into practical solutions by rapidly leveraging massive amounts of data processed via deep learning algorithms. There is a necessity to validate these innovative tools when integrated into clinical practice. Methods This study evaluated the performance of the Hologic Genius Digital Diagnostics System (HGDDS) with a cohort of 890 previously reviewed and diagnosed ThinPrep Papanicolaou (Pap) tests with the intent to deploy this system for routine clinical use. The study included all diagnostic categories of The Bethesda System, with follow‐up tissue sampling performed within 6 months of abnormal Pap test results to serve as the ground truth. Results The HGDDS demonstrated excellent performance in detecting significant Pap test findings, with close to 100% sensitivity (98.2%–100%) for cases classified as atypical squamous cells of undetermined significance and above within a 95% confidence interval and a high negative predictive value (92.4%–100%). Conclusions The HGDDS streamlined workflow, reduced manual workload, and functioned as a stand‐alone system.

AICyte‐alone capabilities as an independent screener for triaging cervical cytology using a 50% negative cutoff value

AbstractBackgroundAICyte has previously demonstrated a potential role in cervical cytology screening for reducing the workload by using a 50% negative cutoff value. The aim of the current study is to evaluate this hypothesis.MethodsThe authors used the Ruiqian WSI‐2400 (with the registered trademark AICyte) to evaluate a collection of 163,848 original cervical cytology cases from 2018 to 2023 that were collected from four different hospital systems in China. A breakdown of cases included 46,060 from Shenzhen, 67,472 from Zhengzhou, 25,667 from Shijiazhuang, and 24,649 from Jinan. These collected cases were evaluated using the AICyte system, and the data collected were statistically compared with the original interpretative results.ResultsIn 98.80% of all artificial intelligence cases that were designated as not needing further review, the corresponding original diagnosis was also determined to be negative. For any cases that were designated atypical squamous cells, cannot exclude high‐grade squamous intraepithelial lesion or higher, the sensitivity and negative predictive value were 90.77% and 98.80%, respectively. The sensitivity and negative predictive value were greater in cases designated as low‐grade squamous intraepithelial lesion or higher at 98.92% and 99.94%, respectively. Of the 49 low‐grade squamous intraepithelial lesion or higher that were designed by AICyte as not needing further review, the cytohistologic correlation revealed eight cases of cervical intraepithelial neoplasia 1 and 18 negative cases; and the remaining cases were without histologic follow‐up. In practice, AICyte used at a 50% negative cutoff value could reduce the anticipated workload if a protocol were implemented to label cases that qualified within the negative cutoff value as not needing further review, thereby finalizing the case as negative for intraepithelial lesions and malignancy.ConclusionsFor pathologic practices that do not have cytotechnologists or in which the workflow is sought to be optimized, the artificial intelligence system AICyte alone to be an independent screening tool by using a 50% negative cutoff value, which is a potential assistive method for cervical cancer screening.

The significance of extensive HPV genotyping for cervical high-grade neoplasia among women with atypical glandular cells

Abstract Objectives To examine the associated risk of cervical intraepithelial neoplasm grade 3+ (CIN3+) lesions in patients with AGC and extensive human papillomavirus (HPV) genotyping. Methods Cases with atypical glandular cell (AGC) interpretation on a Papanicolaou (Pap) test were identified along with associated extensive HPV genotyping and histologic follow-up results. Results Within this cohort of 469,694 Pap tests, 0.4% were diagnosed as AGCs. In total, 1267 cases had concurrent high-risk HPV (hrHPV) genotyping, and 40.3% were hrHPV positive. The percentage of AGC cases with cervical CIN3+ on histologic follow-up was 52.2% when hrHPV was positive, whereas it was 4.9% with a negative hrHPV result. The top 5 hrHPV genotypes associated with cervical CIN3+ in this cohort were HPV16, HPV18, HPV58, HPV52, and HPV33. Indeed, 92.8% of the hrHPV-associated CIN3+ lesions identified in this cohort were positive for at least one of these HPV genotypes. The sensitivity of detecting cervical CIN3+ lesions was 85.6% with the top 5 hrHPV genotypes (HPV16/18/58/52/33) and only increased to 89.0% when the additional 12 genotypes were included. Conclusions In patients with an AGC Pap, the risk of having a cervical CIN3+ lesion is greatly increased by positivity for hrHPV types 16, 18, 58, 52, and/or 33. Incorporating comprehensive HPV genotyping into AGC cytology allows for refined risk stratification and more tailored management strategies.

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.

Assessment of Efficacy and Accuracy of Cervical Cytology Screening With Artificial Intelligence Assistive System

The role of artificial intelligence (AI) in pathology offers many exciting new possibilities for improving patient care. This study contributes to this development by identifying the viability of the AICyte assistive system for cervical screening, and investigating the utility of the system in assisting with workflow and diagnostic capability. In this study, a novel scanner was developed using a Ruiqian WSI-2400, trademarked AICyte assistive system, to create an AI-generated gallery of the most diagnostically relevant images, objects of interest (OOI), and provide categorical assessment, according to Bethesda category, for cervical ThinPrep Pap slides. For validation purposes, 2 pathologists reviewed OOIs from 32,451 cases of ThinPrep Paps independently, and their interpretations were correlated with the original ThinPrep interpretations (OTPI). The analysis was focused on the comparison of reporting rates, correlation between cytological results and histologic follow-up findings, and the assessment of independent AICyte screening utility. Pathologists using the AICyte system had a mean reading time of 55.14 seconds for the first 3000 cases trending down to 12.90 seconds in the last 6000 cases. Overall average reading time was 22.23 seconds per case compared with a manual reading time approximation of 180 seconds. Usage of AICyte compared with OTPI had similar sensitivity (97.89% vs 97.89%) and a statistically significant increase in specificity (16.19% vs 6.77%) for the detection of cervical intraepithelial neoplsia 2 and above lesions. When AICyte was run alone at a 50% negative cutoff value, it was able to read slides with a sensitivity of 99.30% and a specificity of 9.87%. When AICyte was run independently at this cutoff value, no sole case of high-grade squamous intraepithelial lesions/squamous cell carcinoma squamous lesion was missed. AICyte can provide a potential tool to help pathologists in both diagnostic capability and efficiency, which remained reliable compared with the baseline standard. Also unique for AICyte is the development of a negative cutoff value for which AICyte can categorize cases as "not needed for review" to triage cases and lower pathologist workload. This is the largest case number study that pathologists reviewed OOI with an AI-assistive system. The study demonstrates that AI-assistive system can be broadly applied for cervical cancer screening.

Clinical performance of the aptima HPV assay in 4196 women with positive high‐risk HPV and ASC‐US cytology: A large women hospital experience

AbstractBackgroundDespite Aptima assay as the latest US Food Drug Administration (FDA)‐approved high‐risk human papillomavirus (hrHPV) test has been implemented as an adjunct in cervical cancer screening for years, histological follow‐up data remain limited with respect to its performance in women with ASC‐US Pap tests and positive hrHPV results.MethodsCases with results of ASC‐US cytology and positive hrHPV by Aptima assay during the period 06/ 2015–02/2017 were retrieved from archived pathology reports. Immediate histological follow‐up results were analyzed within 6 months interval after cotesting.ResultsAmong 4196 women with ASC‐US Pap tests and positive hrHPV, 51.1% of them had the immediate histological follow‐up within 6 months. With positive Aptima hrHPV as the adjunct, 46.5% (95%CI 46.2–46.8) of ASC‐US women were found to have cervical intraepithelial neoplasia type 1 (CIN1); 8.8% (95%CI 8.1‐9.5) women were detected CIN2+ lesion including eight adenocarcinoma in‐situ (AIS)s. CIN2+ detection rates were highest in women under 25 (15.4%, n = 65), when comparison with different age cutoffs, younger age women had higher CIN2+ lesion detection rate than that in older group (P <.01).ConclusionThis is by far one of the largest retrospective studies to analyze the histological follow‐up results of ASC‐US women with positive hrHPV tested by Aptima hrHPV mRNA assay. The results indicated that younger women with ASC‐US and positive hrHPV testing have highest risk of developing high grade CIN lesions as compared to the older women. Lastly, with positive HPV as the adjunct, 55.3% (1186/2145) of ASC‐US women will result in the positive finding on histological follow‐up.

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.

Immediate histologic correlation in women with atypical squamous cells of undetermined significance cytology and positive high‐risk HPV: A retrospective review of 6000 cases in a large academic women's hospital

BackgroundPrevious studies of the histologic correlation in women who have atypical squamous cells of undetermined significance cytology (ASC‐US) and are positive for high‐risk human papillomavirus (hrHPV+) have predominantly utilized the Hybrid Capture 2 (HC2) test, whereas the use of other US Food and Drug Administration (FDA)‐approved methods is relatively limited.MethodsCases of ASC‐US/hrHPV+ that were tested using HC2, Cervista, or Aptima were retrieved, and the immediate histologic correlations were analyzed.ResultsOverall, 53.9% (n = 3238) of women with ASC‐US/hrHPV+ had immediate histologic correlation. The detection rates for grade 1 cervical intraepithelial neoplasia (CIN1) were similar among the 3 methods (37.1%‐41.8%), while the overall detection rates for grade 2 CIN or higher (CIN2+) were much lower (5.1%‐9.0%). CIN2+ detection rates were similar among different age groups for HC2 testing, whereas for Cervista and Aptima testing, detection rates were highest in the youngest group (age <25 years) and decreased with age. Statistical analyses revealed that the CIN2+ detection rate was significantly higher in younger women who were tested with Cervista.ConclusionThese hrHPV testing methods revealed low CIN2+ detection rates in women with ASC‐US/hrHPV+ but demonstrated different patterns when using age‐stratified analyses. The high rate of CIN2+ detection in women aged <25 years by the Cervista and Aptima testing platforms, but not the HC2 platform, suggest that continual investigation of FDA‐approved clinical hrHPV testing—especially large‐scale, long‐term, prospective studies—is needed to evaluate the best options for management of ASC‐US/hrHPV+ in this age group.

What Constitutes Optimal Cervical Screening for Young Women Ages 21 to 29 Years?

Human Papillomavirus (HPV) 16 and 18/45 Genotyping-Directed Follow-up of Women With Messenger RNA HPV-Positive, Cytology-Negative Cervical Screening Test Results

Abstract Objectives In this study, we sought to correlate genotype test results for human papillomavirus (HPV) types 16, 18, and 45 with histopathologic follow-up diagnoses in patients with messenger RNA (mRNA) high-risk HPV-positive, cytology-negative results. Methods We identified 1,157 patients with mRNA HPV-positive, cytology-negative cervical screening test results between June 2015 and June 2018. Reflex HPV 16/18/45 genotype results were documented in 1,018 women aged 30 years or older, 318 of whom had follow-up within 18 months. Results Histopathologic findings of cervical intraepithelial neoplasia 2 or worse (CIN2+) were diagnosed in 14 of 122 (11.5%) patients positive for HPV 16/18/45 vs in seven of 196 (3.6%) HPV 16/18/45–negative patients. Three patients with high-risk HPV–positive, cytology-negative cervical screening test results were diagnosed with stage I cervical adenocarcinomas following early colposcopic referral and biopsy after HPV 16/18/45–positive genotype results. Conclusions Immediate reflex HPV 16/18/45 genotyping of mRNA HPV-positive, cytology-negative patients led to early colposcopic referral and histopathologic diagnoses of three difficult-to-detect, low-stage, cervical adenocarcinomas and significantly increased overall early detection of CIN2+ lesions.

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.

Aptima HPV messenger RNA testing and histopathologic follow‐up in women with HSIL cytology: A study emphasizing additional review of HPV‐negative cases

BackgroundHigh‐risk human papillomavirus (hrHPV) messenger RNA (mRNA) testing, the Food and Drug Administration–approved testing platform since 2013, has been increasing as a cervical screening alternative to hrHPV DNA testing methods. This study reports the largest routine clinical follow‐up study reported to date of hrHPV mRNA cotesting and histopathologic follow‐up results for women with high‐grade squamous intraepithelial lesion (HSIL) cytology results.MethodsHSIL Papanicolaou test results for women cotested with Aptima hrHPV mRNA testing between June 2015 and November 2020 were analyzed along with recorded histopathologic follow‐up results within 6 months of screening.ResultsAptima hrHPV mRNA–positive results were reported for 95.2% of the cotested HSIL cytology cases (905 of 951). Histopathologic cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was diagnosed on follow‐up in 538 of 701 hrHPV mRNA–positive cases (76.8%) and in 15 of 36 hrHPV mRNA–negative cases (41.7%). Additional reviews of the hrHPV mRNA–negative HSIL cases showed variable interpretations, and confirmatory blinded‐review interpretations of HSIL or atypical squamous cells, cannot exclude high‐grade squamous intraepithelial lesion were more likely in cases with histopathologic CIN2+ (77.5% [93 of 120]) than those with cervical intraepithelial neoplasia grade 1 or negative findings (63.1% [101 of 160]; P < .01).ConclusionsThis large routine‐clinical‐practice study confirms the previously reported high sensitivity of hrHPV mRNA testing for the detection of high‐grade cervical dysplasia and cervical cancers. The blinded‐review findings indicate that additional cytology review may be helpful for confirming an interpretation of HSIL in daily practice, especially for hrHPV‐negative HSIL cases.

The Clinical Utility of Extended High-Risk HPV Genotyping in Women With ASC-US Cytology

AbstractObjectivesExtended testing for high-risk human papillomavirus genotypes (hrHPVGTs) is increasingly investigated for risk stratification in cervical cancer screening.MethodsAge and hrHPVGT results from 16,993 women with atypical squamous cells of undetermined significance (ASC-US) cytology between November 2015 and August 2021 were studied and correlated with available histopathologic findings within 6 months.ResultsHigh-risk human papillomavirus (hrHPV)–positive rate was 66.9% in women with ASC-US cytology, and the most prevalent genotypes were HPV 52 (20.9%), 16 (15.7%), and 58 (12.8%). Single hrHPV genotypes and multiple HPV genotypes were detected in 77.2% and 22.8% of women with hrHPV-positive results. Cervical intraepithelial neoplasia grade 2 or more (CIN2+) severe lesions were identified in 19.5% of women with hrHPV-positive ASC-US. The greatest risk for CIN2+ was found in single genotype infections with HPV 16 (33.1%), followed by women with multiple genotype infections, including HPV 16 (32.7%), 82 (30.8%), and 31 (30.0%). hrHPVGT testing for genotypes 16, 31, 35, 45, 82, 58, 33, 52, and 18 was identified in 91.9% (965/1,050) of CIN2+ cases, with 88.9% sensitivity, 43.2% specificity, positive predictive value of 23.9%, and negative predictive value of 95.1%.ConclusionsExtended hrHPV genotyping for women with ASC-US cytology could identify those hrHPV genotypes (HPV 16, 31, 35, 45, 82, 58, 33, 52, 18) associated with higher risk of CIN2+ and allows for refined risk stratification of women being screened.

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.;

Nationwide Prevalence and Genotype Distribution of High-Risk Human Papillomavirus Infection in China

Abstract Objectives Extended high-risk human papillomavirus (hrHPV) genotype testing has recently been introduced in routine cervical cancer screening. Changes in national and regional hrHPV genotype prevalence offer an objective baseline indicator of the future impact of mass HPV vaccination and HPV-based cervical screening. Methods This retrospective study reports nationwide hrHPV genotyping results from July 2018 to June 2019 in 29 KingMed Diagnostics laboratories throughout China. Results In total, 2,458,227 hrHPV genotyping results were documented from KingMed’s nationwide laboratory database during the study period. The overall prevalence of hrHPV-positive results was 19.1%, with twin peaks for highest hrHPV infection rates in women younger than 30 years of age (22.0%) and 50 years of age and older (21.8%). The most frequently detected hrHPV genotypes were HPV-52 (4.7%), HPV-16 (3.4%), HPV-53 (2.5%), HPV-58 (2.4%), HPV-51 (2.0%), and HPV-68 (1.6%). Overall, hrHPV-positive results varied regionally from 15.3% to 24.4%. Conclusions Nationwide hrHPV genotyping results from KingMed laboratories offer a baseline for measuring the future impact of large-scale HPV vaccination. High hrHPV infection rates in older (≥50 years) Chinese women likely reflect the limited extent of cervical screening in China. High rates of hrHPV infection and variable regional hrHPV genotype distribution may represent limiting factors for cost-effective implementation of hrHPV-based cervical screening in China.

Single and Multiple High-Risk Human Papillomavirus Infections in Histopathologically Confirmed Cervical Squamous Lesions: Incidences, Distribution, and Associated Detection Rates for Precancerous and Cancerous Lesions

Coinfection with multiple high-risk human papillomavirus (hrHPV) is frequently observed in cervical specimens; however, the clinical significance of concomitant multiple hrHPV infections is poorly understood, and the published results remain inconsistent. A retrospective study at a tertiary care institution was performed, evaluating Tellgenplex human papillomavirus (HPV) 27 genotyping or YanengBio HPV 23 genotyping results and immediate cervical histologic diagnosis (within 6 months after HPV genotyping), between November 2015 and October 2022. Among 49,299 cases with hrHPV genotyping and histologic diagnosis, 24,361 cases were diagnosed as cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma. Among women with cervical squamous lesions, 86.5% (21,070/24,361) had hrHPV infections, and concomitant multiple hrHPV infections accounted for 24.7% of hrHPV-positive cases (5210/21,070). The hrHPV-positive rates in these cervical squamous lesions increased progressively with disease severity; however, the percentages of concomitant multiple hrHPV infection rates among hrHPV-positive cases decreased significantly with increasing degree of squamous abnormalities. There was no increased detection rate of CIN3+ (CIN3 and squamous cell carcinoma) in cases with concomitant 2 or 3 hrHPV genotype infections when compared with those with corresponding single hrHPV infections. Conversely, some combinations of multiple hrHPV infections demonstrated a decrease in the detection rates of CIN3+ lesions. In this large cohort, our results demonstrated that multiple hrHPV infections do not carry an increased risk for developing CIN3+ lesions when compared to the corresponding single-genotype infection. The reduced risk of CIN3+ in women infected with some combinations of hrHPV genotypes compared to those with single-genotype infections supports the concept of intergenotypic competition of hrHPV genotypes in cervical squamous lesions.

Associations of Single Versus Multiple Human Papillomavirus Infections With the Prevalence of Cervical Intraepithelial Neoplasia 2/3 and Squamous Cell Carcinoma Lesions: Human Papillomavirus Type–Specific Attribution

The risk of developing cervical squamous lesions in women with multiple high-risk human papillomavirus (hrHPV) infections is uncertain. The aim of this retrospective study was to investigate the type-specific attribution and phylogenetic effects of single and multiple hrHPV subtypes in cervical squamous lesions. All cases with cervical histopathologic diagnosis and human papillomavirus (HPV) genotyping results in the 6 months preceding biopsy from October 2018 to December 2022 were studied and analyzed. Over the study period, 70,361 cases with histopathologic follow-up and prior HPV genotyping were identified. The hrHPV-positive rate was 55.6% (39,104/70,361), including single hrHPV detected in 27,182 (38.6%), 2 types of hrHPV detected in 8158 (11.6%), and 3 types of hrHPV detected in 2486 (3.5%). Among 16,457 cases with a histologically diagnosed squamous lesion (cervical intraepithelial neoplasia 1: 11411; cervical intraepithelial neoplasia 2/3: 4192; squamous cell carcinoma: 854 cases), the prevalence of single hrHPV infection increased, but the rate of multiple concomitant hrHPV infections showed negative association as the degree of squamous lesions increased. Among women with a single HPV16 infection, cervical intraepithelial neoplasia 2/3 and squamous cell carcinoma (CIN2+) diagnostic rate was 30.6%, and it increased to 47.6% when coinfected with HPV33 (P < .001) but significantly decreased when coinfected with all other hrHPV types (P < .05). By comparing CIN2+ diagnostic rates in 40 most common 2 types of hrHPV infections with related single hrHPV infection, CIN2+ rates were decreased in 12 combinations (30.0%), equivalent in 26 combinations (65.0%), and increased in 2 combinations (5.0%). The cases with 3 types of HPV infections reduced the risk for CIN2+ compared with related single HPV infections. HPV16+52+53, HPV16+52+68, HPV16+52+51, HPV16+39+52, and HPV16+58+53 significantly decreased the risk of CIN2+ compared with HPV16 single infection (P < .05). This study demonstrates that multiple hrHPV infections are not associated with cumulatively higher risk for CIN2+ development, suggesting that oncogenic progression of multiple hrHPV-associated cervical squamous lesions is neither synergistic nor a cumulative effect at the phylogenetic level, possibly a way of competitive interference.