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

Background Extended high‐risk human papillomavirus (hrHPV) genotype testing (hrHPVGT) has emerged as a new strategy to help optimize the efficiency of hrHPV triage. Methods Women 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. Results In 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+. Conclusions hrHPVGT for women who have ASC‐US cytology allows for risk stratification capable of optimizing the efficiency of triage for hrHPV‐positive women. Extended human papillomavirus (HPV) genotyping reveals that HPV types 16, 33, 82, 18, 31, 45, 58, and 52 identify 95% of high‐grade cervical intraepithelial neoplasia with 90.8% sensitivity and 53.8% specificity. This genotyping allows for risk stratification capable of optimizing the efficiency of triage for patients who are positive for high‐risk HPV and have a finding of atypical squa