采用 HPV 基因分型检测对 ASC-US 细胞学结果的女性进行宫颈癌风险分层：来自中国的一项大样本回顾性研究。

Risk stratification for cervical neoplasia using extended high-risk HPV genotyping in women with ASC-US cytology: A large retrospective study from China.

机构信息

Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.

Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

出版信息

Cancer Cytopathol. 2022 Apr;130(4):248-258. doi: 10.1002/cncy.22536. Epub 2021 Dec 7.

DOI:10.1002/cncy.22536

PMID:34874615

Abstract

BACKGROUND

Extended high-risk human papillomavirus (hrHPV) genotype testing (hrHPVGT) has emerged as a new strategy to help optimize the efficiency of hrHPV triage.

METHODS

Women with an atypical squamous cells of undetermined significance (ASC-US) cervical Papanicolaou test result who underwent hrHPVGT between October 2017 and May 2021 at the Obstetrics and Gynecology Hospital of Fudan University in Shanghai, China, were studied. For hrHPVGT, a proprietary multiplex real-time polymerase chain reaction assay was used. hrHPVGT and viral load test results in selected patients were correlated with histopathologic follow-up findings available within 6 months.

RESULTS

In total, 17,235 women with ASC-US cytology who had hrHPVGT results were identified in the Obstetrics and Gynecology Hospital of Fudan University database. The hrHPV-positive rate was 61.8%, and the most prevalent hrHPV genotypes were type 52 (HPV52) (16%), HPV16 (11.3%), HPV58 (10.2%), and HPV53 (8.4%). Single hrHPV genotypes were detected in 65.9% of women with hrHPV-positive results, and multiple genotypes were detected in 34.1%. Histopathologic cervical findings within 6 months were available in 5627 hrHPV-positive women and 2223 hrHPV-negative women. High-grade cervical intraepithelial lesions or cervical cancer (cervical intraepithelial neoplasia 2 or greater [CIN2+]) were identified in 7.5% of hrHPV-positive women who had ASC-US cytology and in 0.9% of hrHPV-negative women who had ASC-US cytology. The greatest risk for CIN2+ was in single hrHPV genotype infections with HPV16 (21.1%), HPV33 (15.2%), HPV82 (10%), and HPV18 (9.9%). hrHPVGT for genotypes HPV16, HPV33, HPV82, HPV18, HPV31, HPV45, HPV58, and HPV52 identified 95% of CIN2+ cases with 90.8% sensitivity, 53.8% specificity, a positive predictive value of 10.2%, and a negative predictive value of 99%. A significantly increased viral load was associated only with women who had HPV16-related CIN2+.

CONCLUSIONS

hrHPVGT for women who have ASC-US cytology allows for risk stratification capable of optimizing the efficiency of triage for hrHPV-positive women.

摘要

背景

扩展高危型人乳头瘤病毒（hrHPV）基因型检测（hrHPVGT）已成为一种新策略，有助于优化 hrHPV 分流的效率。

方法

本研究纳入了 2017 年 10 月至 2021 年 5 月在中国上海复旦大学妇产科医院进行 hrHPVGT 的因非典型鳞状细胞意义不明确（ASC-US）宫颈巴氏涂片检查结果异常的女性。hrHPVGT 采用专有的多重实时聚合酶链反应检测。在 6 个月内获得了 hrHPVGT 和病毒载量检测结果与组织病理学随访结果的相关性。

结果

在复旦大学妇产科医院数据库中，共确定了 17235 例 ASC-US 细胞学检查的 hrHPV 阳性女性。hrHPV 阳性率为 61.8%，最常见的 hrHPV 基因型为 HPV52（16%）、HPV16（11.3%）、HPV58（10.2%）和 HPV53（8.4%）。65.9%的 hrHPV 阳性女性检测到单一的 hrHPV 基因型，34.1%的女性检测到多种基因型。在 5627 例 hrHPV 阳性女性和 2223 例 hrHPV 阴性女性中，在 6 个月内获得了组织病理学宫颈发现。在 ASC-US 细胞学检查结果异常的 hrHPV 阳性女性中，有 7.5%的女性发现高级别宫颈上皮内瘤变或宫颈癌（宫颈上皮内瘤变 2 级或更高级别[CIN2+]），在 ASC-US 细胞学检查结果正常的 hrHPV 阴性女性中，有 0.9%的女性发现 CIN2+。在 HPV16（21.1%）、HPV33（15.2%）、HPV82（10%）和 HPV18（9.9%）单一基因型感染的女性中，CIN2+的风险最高。针对 HPV16、HPV33、HPV82、HPV18、HPV31、HPV45、HPV58 和 HPV52 基因型的 hrHPVGT 检测可发现 95%的 CIN2+病例，敏感性为 90.8%，特异性为 53.8%，阳性预测值为 10.2%，阴性预测值为 99%。仅与 HPV16 相关的 CIN2+女性的病毒载量显著增加有关。