Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Department of Biological Sciences, Center for Human Health and the Environment, North Carolina State University, Raleigh, North Carolina.
Cancer Epidemiol Biomarkers Prev. 2022 Aug 2;31(8):1564-1571. doi: 10.1158/1055-9965.EPI-22-0054.
High-risk human papillomavirus (hrHPV) testing is utilized in primary cervical cancer screening, generally along with cytology, to triage abnormalities to colposcopy. Most screening-based hrHPV testing involves pooled detection of any hrHPV or of HPV16/18. Cervical neoplasia progression risks based on extended hrHPV genotyping-particularly non-16/18 hrHPV types-are not well characterized. HPV genotype-specific incidence of high-grade cervical intraepithelial neoplasia or more severe (CIN2+) following an abnormal screening result was examined.
We assessed a US-based prospective, multiracial, clinical cohort of 343 colposcopy patients with normal histology (n = 226) or CIN1 (n = 117). Baseline cervical samples underwent HPV DNA genotyping, and participants were followed up to 5 years. Genotype-specific CIN2+ incidence rates (IR) were estimated with accelerated failure time models. Five-year CIN2+ risks were estimated nonparametrically for hierarchical hrHPV risk groups (HPV16; else HPV18/45; else HPV31/33/35/52/58; else HPV39/51/56/59/68).
At enrollment, median participant age was 30.1 years; most (63%) were hrHPV-positive. Over follow-up, 24 participants progressed to CIN2+ (7.0%). CIN2+ IR among hrHPV-positive participants was 3.4/1,000 person-months. CIN2+ IRs were highest for HPV16 (8.3), HPV33 (7.8), and HPV58 (4.9). Five-year CIN2+ risk was higher for HPV16 (0.34) compared with HPV18/45 (0.12), HPV31/33/35/52/58 (0.12), and HPV39/51/56/59/68 (0.16) (P = 0.05).
Non-16/18 hrHPV types are associated with differential CIN2+ progression rates. HPV16, 33, and 58 exhibited the highest rates over 5 years. HPV risk groups warrant further investigation in diverse US populations.
These novel data assessing extended HPV genotyping in a diverse clinical cohort can inform future directions to improve screening practices in the general population.
高危型人乳头瘤病毒（hrHPV）检测用于宫颈癌的初筛，通常与细胞学联合应用，对异常情况进行阴道镜检查。大多数基于筛查的 hrHPV 检测涉及对任何 hrHPV 或 HPV16/18 的混合检测。基于扩展的 HPV 基因分型的宫颈癌进展风险，尤其是非 16/18 型 HPV 类型，尚未得到很好的描述。本研究旨在评估异常筛查结果后 HPV 基因型特异性的高级别宫颈上皮内瘤变或更严重病变（CIN2+）的发生情况。
我们评估了美国一项前瞻性、多民族、临床队列的 343 名阴道镜检查患者的资料，其中包括 226 名组织学正常的患者和 117 名 CIN1 患者。基线宫颈样本进行 HPV DNA 基因分型，随访时间为 5 年。使用加速失效时间模型估计 HPV 基因型特异性 CIN2+发生率（IR）。对于分层的 hrHPV 风险组（HPV16；HPV18/45 以外；HPV31/33/35/52/58 以外；HPV39/51/56/59/68 以外），采用非参数法估计 5 年 CIN2+风险。
入组时，中位年龄为 30.1 岁，大多数（63%）为 hrHPV 阳性。在随访期间，有 24 名患者进展为 CIN2+（7.0%）。在 hrHPV 阳性患者中，CIN2+IR 为 3.4/1000 人-月。HPV16（8.3%）、HPV33（7.8%）和 HPV58（4.9%）的 CIN2+IR 最高。与 HPV18/45（0.12）、HPV31/33/35/52/58（0.12）和 HPV39/51/56/59/68（0.16）相比，HPV16 的 5 年 CIN2+风险更高（P=0.05）。
非 16/18 型 hrHPV 与不同的 CIN2+进展率相关。HPV16、33 和 58 在 5 年内的发生率最高。HPV 风险组需要在不同的美国人群中进一步研究。
本研究评估了 HPV 基因分型在不同临床队列中的应用，为进一步完善普通人群的筛查策略提供了依据。
