Department of Obstetrics and Gynecology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Women's Healthcare Center, Otaru General Hospital, Otaru, Japan.
Cancer Sci. 2018 Jun;109(6):2003-2012. doi: 10.1111/cas.13608. Epub 2018 May 31.
Although cytology-based screening programs have significantly reduced mortality and morbidity from cervical cancer, the global consensus is that primary human papillomavirus (HPV) testing for cervical screening increases detection of high-grade cervical intraepithelial neoplasia (CIN) and invasive cancer. However, the optimal triage strategy for HPV-positive women to avoid over-referral to colposcopy may be setting specific. As Japan requires data that have been generated domestically to modify screening guidelines, we conducted a 3-year prospective study, COMparison of HPV genotyping And Cytology Triage (COMPACT), to evaluate the potential role of HPV16/18 partial genotyping and cytology for primary HPV screening. In total, 14 642 women aged 20 to 69 years undergoing routine screening at 3 centers in Hokkaido were enrolled. Conventional cytology and HPV testing were carried out. Women with abnormal cytology or HPV16/18 positivity underwent colposcopy. Those with 12 other high-risk (hr) HPV types underwent repeat cytology after 6 months. Primary study endpoints were detection of high-grade cervical disease defined as CIN2/CIN3 or greater as determined by consensus pathology. Prevalence of cytological abnormalities was 2.4%. hrHPV, HPV 16, and HPV 18 were detected in 4.6%, 0.9%, and 0.3% of women, respectively. HPV16/18 were detected in all (8/8) invasive cervical cancers and in all (2/2) adenocarcinomas in situ. Both cytological abnormalities and hrHPV positivity declined with increasing age. This is the first Japanese study to investigate the role of partial genotyping and cytology in an HPV-based screening program. Results should help policy-makers develop guidelines for future cervical screening programs and management of cervical abnormalities based on HPV genotype.
虽然基于细胞学的筛查计划显著降低了宫颈癌的死亡率和发病率，但全球共识认为，用于宫颈癌筛查的人乳头瘤病毒（HPV）初筛检测增加了对高级别宫颈上皮内瘤变（CIN）和浸润性癌的检出率。然而，HPV 阳性女性避免过度转诊行阴道镜检查的最佳分流策略可能因具体情况而异。由于日本要求对国内产生的数据进行修改以调整筛查指南，我们开展了一项为期 3 年的前瞻性研究，即 HPV 基因分型和细胞学分流比较（COMPACT），以评估 HPV16/18 部分基因分型和细胞学在 HPV 初筛中的潜在作用。共纳入了北海道 3 个中心的 14642 名 20-69 岁的常规筛查女性。进行了常规细胞学和 HPV 检测。细胞学异常或 HPV16/18 阳性的女性进行阴道镜检查。其他 12 种高危（hr）HPV 型阳性的女性在 6 个月后行重复细胞学检查。主要研究终点是通过共识病理确定的高级别宫颈疾病（CIN2/CIN3 或更高级别）的检出率。细胞学异常的发生率为 2.4%。hrHPV、HPV16 和 HPV18 在分别为 4.6%、0.9%和 0.3%的女性中被检出。所有（8/8）浸润性宫颈癌和所有（2/2）原位腺癌均检测到 HPV16/18。细胞学异常和 hrHPV 阳性均随年龄增长而下降。这是日本首例研究 HPV 初筛中部分基因分型和细胞学作用的研究。结果有助于决策者制定未来基于 HPV 基因型的宫颈癌筛查计划和宫颈异常管理指南。
