Diagnostic value of high‐risk HPV other than type 16/18 in high‐grade cervical neoplasia among cytology‐negative women: A multicenter retrospective study

BACKGROUND: Human papillomavirus (HPV) is a necessary cause of cervical cancer, and a tool more sensitive than cytology for the early screening of cervical precancers. The two most carcinogenic genotypes HPV 16/18 have been reported in the majority of studies. High‐risk HPVs other than HPV 16/18 (non‐16/18‐hrHPVs) cause approximately a quarter of cervical cancers, and we aimed to analyze the genotype‐specific prevalence, risk and diagnostic efficiency of non‐16/18‐hrHPVs in cervical carcinogenesis among Chinese cytology‐negative women. METHODS: A total of 7043 females who had abnormal cervical testing results from January 2018 to October 2021 were enrolled, among them 3091 were cytology‐negative. Descriptive statistics was used to estimate the HPV genotype‐specific prevalence, and multivariable logistic regression was used to estimate the genotype‐specific non‐16/18 hrHPVs risk of cervical carcinogenesis. The evaluation of diagnostic value among HPV genotypes included the possibility of predicting cervical intraepithelial neoplasia grade 2/3 or worse (CIN2+/CIN3+) and the diagnostic efficiency measured by increased referral rate and referral numbers of colposcopies per additional CIN2+/CIN3+ detected. RESULTS: Among HPV‐positive cytology‐negative women, the five dominant genotypes for CIN2+/CIN3+ were HPV 31/33/35/52/58. HPV 52/58/33 had comparatively high sensitivity and specificity in predicting CIN2+/CIN3+, while the referral strategy of multiple HPV58 required 26 colposcopies to detect 1 CIN3+, compared with 14, 12, and 8 required by multiple HPV52, 31, and 33, respectively. CONCLUSIONS: HPV31/33/35/52/58 infections are significant risk factors for cervical lesions, and multiple HPV 31/33/52 infections should be included in the previously recommended HPV16/18 genotyping triage for colposcopy in China, as the benefits of disease prevention may outweigh the disadvantages of increasing requirements for colposcopy services.