Department of Obstetrics and Gynecology, Hokkaido University Faculty of Medicine, Sapporo, Japan.
Hokkaido Center for Environmental and Health Sciences, Sapporo, Japan.
J Gynecol Oncol. 2021 Nov;32(6):e86. doi: 10.3802/jgo.2021.32.e86.
While cytology-based screening programs have significantly reduced mortality and morbidity from cervical cancer, the global consensus is that primary human papillomavirus (HPV) testing increases detection of high-grade cervical intraepithelial neoplasia (CIN) and invasive cancer. However, the optimal triage strategy for HPV+ women to avoid over-referral to colposcopy may be setting specific. We compared absolute and relative risk (RR) of >CIN2/3 within 12 months of a negative cytologic result in women HPV16/18+ compared to those with a 12-other high-risk HPV (hrHPV) genotype to identify women at greatest risk of high-grade disease and permit less aggressive management of women with other hrHPV infections.
Participants were 14,160 women aged 25-69 years with negative cytology participating in the COMparison of HPV genotyping And Cytology Triage (COMPACT) study. Women who were HPV16/18+ were referred to colposcopy. Those with a 12-other hrHPV type underwent repeat cytology after 6 months and those with >abnormal squamous cells of undetermined significance went to colposcopy.
Absolute risk of >CIN2 in HPV16/18+ women was 19.5% (95% CI=12.4%-29.4%). In women 25-29 years and HPV16+ it was 40.0% (95% CI=11.8%-76.9%). Absolute risk of >CIN3 in women HPV16/18+ was 11.0% (95% CI=5.9%-19.6%). For women 30-39 years and HPV16+ it was 23.1% (95% CI=5.0%-53.8%). Overall risk of >CIN2, >CIN3 in women with a 12-other hrHPV HPV type was 5.6% (95% CI=3.1%-10.0%) and 3.4% (95% CI=1.6%-7.2%) respectively. RR of >CIN2, >CIN3 in HPV16/18+ vs. 12-other hrHPV was 3.5 (95% CI=1.7-7.3) and 3.3 (95% CI=1.2-8.8), respectively.
Primary HPV screening with HPV16/18 partial genotyping is a promising strategy to identify women at current/future risk of >CIN2 in Japan without over-referral to colposcopy.
Trial Registration: UMIN Clinical Trials Registry Identifier: UMIN000013203.
细胞学为基础的筛查方案显著降低了宫颈癌的死亡率和发病率，但全球共识认为，人乳头瘤病毒（HPV）的初次检测增加了高级别宫颈上皮内瘤变（CIN）和浸润性癌的检出率。然而，对于 HPV 阳性女性的最佳分流策略，可能因具体情况而异。我们比较了 HPV16/18 阳性与其他 12 种高危型 HPV（hrHPV）的女性在细胞学阴性后 12 个月内发生 >CIN2/3 的绝对风险和相对风险（RR），以确定发生高级别疾病风险最高的女性，并允许对其他 hrHPV 感染的女性进行侵袭性较小的管理。
本研究纳入了年龄在 25-69 岁、细胞学阴性的 14160 名女性，她们参加了 HPV 基因分型和细胞学分流（COMPACT）研究。HPV16/18 阳性的女性被转诊至阴道镜检查，而其他 12 种 hrHPV 阳性的女性则在 6 个月后行重复细胞学检查，如果发现 >非典型鳞状细胞意义不明确，行阴道镜检查。
HPV16/18 阳性女性发生 >CIN2 的绝对风险为 19.5%（95%可信区间：12.4%-29.4%）。在 25-29 岁和 HPV16 阳性的女性中，该风险为 40.0%（95%可信区间：11.8%-76.9%）。HPV16/18 阳性女性发生 >CIN3 的绝对风险为 11.0%（95%可信区间：5.9%-19.6%）。在 30-39 岁和 HPV16 阳性的女性中，该风险为 23.1%（95%可信区间：5.0%-53.8%）。其他 12 种 hrHPV 阳性女性的总体 >CIN2 和 >CIN3 风险分别为 5.6%（95%可信区间：3.1%-10.0%）和 3.4%（95%可信区间：1.6%-7.2%）。HPV16/18 阳性 vs. 其他 12 种 hrHPV 的 >CIN2 和 >CIN3 的 RR 分别为 3.5（95%可信区间：1.7-7.3）和 3.3（95%可信区间：1.2-8.8）。
在日本，使用 HPV16/18 部分基因分型进行原发性 HPV 筛查是一种很有前途的策略，可以识别当前/未来发生 >CIN2 的女性，而不会过度转诊至阴道镜检查。
临床试验注册：UMIN 临床研究注册标识：UMIN000013203。
