Department of Epidemiology and Biostatistics, School of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Diagnosis and Treatment for Cervical Lesions Center, Shenzhen Maternity & Child Healthcare Hospital, Shenzhen, China.
Cancer Med. 2023 Jul;12(13):14794-14805. doi: 10.1002/cam4.6109. Epub 2023 May 18.
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.
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.
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.
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.
人乳头瘤病毒（HPV）是宫颈癌的必要病因，也是细胞学检查更敏感的早期宫颈癌前病变筛查工具。在大多数研究中，报告了两种最具致癌性的基因型 HPV 16/18。除 HPV 16/18 以外的高危型 HPV（非 16/18-hrHPV）约占宫颈癌的四分之一，我们旨在分析在中国细胞学阴性女性中 HPV 非 16/18-hrHPV 与宫颈癌发生的基因型特异性相关性、风险和诊断效率。
共纳入 7043 名 2018 年 1 月至 2021 年 10 月间宫颈检查异常的女性，其中 3091 名为细胞学阴性。采用描述性统计估计 HPV 基因型特异性流行率，采用多变量逻辑回归估计 HPV 非 16/18-hrHPV 与宫颈癌发生的基因型特异性风险。HPV 基因型的诊断价值评估包括预测宫颈上皮内瘤变 2 级/3 级或更高级别病变（CIN2+/CIN3+）的可能性以及通过增加转诊率和每检出 1 例 CIN2+/CIN3+增加的阴道镜转诊数量来评估诊断效率。
在 HPV 阳性细胞学阴性的女性中，预测 CIN2+/CIN3+的前 5 种优势基因型为 HPV 31/33/35/52/58。HPV 52/58/33 在预测 CIN2+/CIN3+方面具有较高的敏感性和特异性，而 HPV58 多重检测的转诊策略需要 26 次阴道镜检查才能检出 1 例 CIN3+，而 HPV52、31 和 33 多重检测分别需要 14、12 和 8 次阴道镜检查。
HPV31/33/35/52/58 感染是宫颈病变的重要危险因素，在中国，HPV16/18 基因分型检测中应增加 HPV31/33/52 多重检测，以作为阴道镜检查的分流策略，因为预防疾病的益处可能大于增加阴道镜服务需求的弊端。
