<p>The Triage Effectiveness of an Extended High-Risk Human Papillomavirus Genotyping Assay for Women with Cytology Showing Atypical Squamous Cells of Undetermined Significance in China</p>

Abstract

Little is known about the performance of extended high-risk human papillomavirus (HR-HPV) genotyping triage of cytology showing atypical squamous cells of undetermined significance (ASC-US). This study aims to evaluate the effectiveness of triage with different HR-HPV genotype models among women with ASC-US. Materials and Methods: In this study, all women who underwent cervical cytology and HR-HPV genotyping were enrolled from 2014 to 2017 in China, and those with cytology showing ASC-US were referred for colposcopy and/or biopsy. The endpoint was histological detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+). The outcome indicators were the sensitivity, specificity, positive predictive values (PPVs), negative predictive values (NPVs) and colposcopy referral rates. Results: In all, 56,788 women were enrolled in this study, and 2658 (4.97%) women were reported to have ASC-US; 10.1% (242/2393) of women with ASC-US were identified as having CIN2+. The HR-HPV infection rate was 95.0% among all women with ASC-US who were identified as CIN2+, and the top five genotypes with prevalence and risk of CIN2+ were HPV16 (OR=26.38), HPV58 (OR=7.04), HPV18 (OR=4.44), HPV33 (OR=3.38), HPV31 (OR=2.97) and HPV52 (OR=2.96). The HPV16/18/31/33/52/58 model achieved higher sensitivity [91.3 (87.8-94.9)], specificity [70.0 (68.1-72.0)], PPV [25.5 (22.4-28.2)] and NPV [98.6 (97.3-98.7)] for the triage of ASC-US patients than the other HR-HPV-type combination models, but the colposcopy referral rate (36.2%) was significantly lower than that of the recommended HR-HPV nongenotyping model (47.6%). Conclusion: This study confirms that the specific HR-HPV genotype HPV16/18/31/33/52/ 58 is an alternative strategy for ASC-US triage and can effectively reduce the high burden of colposcopy referrals in China.

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

“…These data confirm findings from other recent Chinese studies that smaller genotype subsets for hrH-PVGT may provide more efficient target groups for triage to diagnostic testing after ASC-US cytology results [11][12][13][14] and could assist in efforts to more efficiently diagnose histopathologic high-grade intraepithelial lesions and cancers. The hrHPVGT methods used were different in each of these other Chinese studies, and only 1 study tested for HPV82, which is sometimes classified as a possibly carcinogenic HPV genotype.…”

“…The Validation of HPV Genotyping Tests (VALGENT) framework has been developed as a result and represents an international cooperative effort designed to evaluate HPV assays with genotyping capabilities 8 . hrHPVGT has been proposed as a way to enhance the specificity of cervical screening that limits the need for colposcopic referral and follow‐up diagnostic excisional procedures 9‐18 . Cervical screening using routine cytology and hrHPVGT has been widely used at the Obstetrics and Gynecology Hospital of Fudan University (OGHFU) in Shanghai, China's largest academic women's hospital 19 .…”

“…8 hrHPVGT has been proposed as a way to enhance the specificity of cervical screening that limits the need for colposcopic referral and follow-up diagnostic excisional procedures. [9][10][11][12][13][14][15][16][17][18] Cervical screening using routine cytology and hrHPVGT has been widely used at the Obstetrics and Gynecology Hospital of Fudan University (OGHFU) in Shanghai, China's largest academic women's hospital. 19 Given the size of the OGHFU data set, the available histopathologic follow-up, and the common use in many countries of adjunctive hrHPV testing without genotyping as a triage tool in women who have indeterminate abnormal cytology results, we decided to specifically analyze the performance of hrHPVGT at OGHFU in women who had atypical squamous cells of undetermined significance (ASC-US) cytology results.…”

Analysis of the related factors of atypical squamous cells of undetermined significance (ASC-US) in cervical cytology of post-menopausal women

“…reported that the top five genotypes with respect to prevalence and risk of CIN2+ were HPV16, 58,18, 33, 31, and 52. The HPV16, 18, 31, 33, 52 and 58 model achieved higher sensitivity (91.3%) and specificity (70.0%) for the triage of patients with ASC-US than the other HR-HPV-type combination models ( Pan et al., 2020 ). In the current study, we observed that the CIN2+ detection rate of HPV16/18 positive patients with ASC-US was significantly higher than that of the other high-risk HPV-positive groups, and the five highest-risk HPV genotypes were HPV16, 52, 58, 18, and 33.…”

“…Through a systematic review, Pan et al. demonstrated that the detection rate of CIN2+ in the patients with ASC-US was 10.1% ( Pan et al., 2020 ). Tao et al.…”