Ye Yuhong, Jones Terrel, Wang Tiannan, Zeng Xianxu, Liu Yang, Zhao Chengquan
Department of Pathology, the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China.
Department of Pathology, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Gynecol Obstet Clin Med. 2024 Apr;4(1). doi: 10.1136/gocm-2024-000005.
Across cervical squamous and glandular lesions, a spectrum of human papillomavirus (HPV) genotypes has been identified. This review aims to provide a comprehensive summary detailing the distribution and profile of HPV genotypes detected in cervical lesions, leveraging insights from histological and cytological findings. High-risk HPV (HR-HPV) genotypes exhibit varying degrees of oncogenic potential, with HPV16 and HPV18 identified as the most prevalent and oncogenic types. The distribution of HR-HPV genotypes varies among different degrees of the cervical lesions and varies between squamous and glandular neoplasia. HPV16 is predominantly associated with severe lesions (precancers and carcinomas), while HPV18 demonstrates a significantly higher prevalence in endocervical as compared with squamous neoplasia. The distribution of HR-HPV in severe squamous lesions is complex, involving many HR-HPV genotypes in addition to HPV16, while the distribution of HR-HPV genotypes in endocervical glandular lesions is mainly limited in HPV18 and HPV16. Large datasets from China have identified the three most common HR-HPV genotypes in this population as stratified by diagnostic category: HPV52, HPV16, HPV58 in histologically negative cases and cervical intraepithelial neoplasia 1 (CIN1); HPV16, HPV52, HPV58 in CIN2/3; HPV16, HPV58, HPV52 or HPV18 in squamous cell carcinoma (SCC); HPV16, HPV18 and HPV52 in endocervical adenocarcinoma in situ (AIS), invasive adenocarcinoma, as well as mixed squamous and glandular lesions. HPV33 is the fourth most common HPV type in CIN2/3 and SCC, while HPV45 occurs more commonly in AIS and adenocarcinoma, compared with squamous lesions. The prevalence and distribution of multiple HR-HPV coinfections vary across different cervical diseases. The clinical significance and pathogenesis of these multiple HR-HPV infections remain uncertain, although recent two large studies demonstrate that multiple HR-HPV infections are not associated with cumulatively higher risk of high-grade cervical squamous lesion development, suggesting competitive and/or cooperative interactions among HPV genotypes. Extensive HPV genotyping aids in risk assessment and optimising clinical approaches for women with mild abnormalities in Pap cytology. Women with atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) Pap test results and with the infection of some HR-HPV genotypes carry a very low risk of high-grade cervical lesions. HPV genotyping can allow for risk stratification and triage optimisation for these HR-HPV-positive women. Women with atypical glandular cell (AGC) Pap test results showed a specific HPV genotyping pattern and extended HPV genotyping may be helpful for the clinical management of AGCs. Continual advancements in clinical guidelines integrating extended genotyping would increase diagnostic accuracy and refine strategies in clinical management.
在宫颈鳞状和腺性病变中,已鉴定出一系列人乳头瘤病毒(HPV)基因型。本综述旨在提供一份全面的总结,详细说明宫颈病变中检测到的HPV基因型的分布和特征,借鉴组织学和细胞学发现的见解。高危HPV(HR-HPV)基因型具有不同程度的致癌潜力,其中HPV16和HPV18被确定为最常见和致癌性最强的类型。HR-HPV基因型的分布在宫颈病变的不同程度之间有所不同,在鳞状和腺性肿瘤之间也有所不同。HPV16主要与严重病变(癌前病变和癌)相关,而与鳞状肿瘤相比,HPV18在内宫颈中的患病率显著更高。HR-HPV在严重鳞状病变中的分布很复杂,除HPV16外还涉及许多HR-HPV基因型,而HR-HPV基因型在内宫颈腺性病变中的分布主要局限于HPV18和HPV16。来自中国的大型数据集已确定该人群中按诊断类别分层的三种最常见的HR-HPV基因型:组织学阴性病例和宫颈上皮内瘤变1(CIN1)中的HPV52、HPV16、HPV58;CIN2/3中的HPV16、HPV52、HPV58;鳞状细胞癌(SCC)中的HPV16、HPV58、HPV52或HPV18;原位宫颈腺癌(AIS)、浸润性腺癌以及混合性鳞状和腺性病变中的HPV16、HPV18和HPV52。HPV33是CIN2/3和SCC中第四常见的HPV类型,而与鳞状病变相比,HPV45在AIS和腺癌中更常见。多种HR-HPV合并感染的患病率和分布在不同的宫颈疾病中有所不同。这些多种HR-HPV感染的临床意义和发病机制仍不确定,尽管最近的两项大型研究表明,多种HR-HPV感染与高级别宫颈鳞状病变发展的累积更高风险无关,这表明HPV基因型之间存在竞争和/或合作相互作用。广泛的HPV基因分型有助于对巴氏细胞学检查有轻度异常的女性进行风险评估和优化临床方法。意义不明确的非典型鳞状细胞(ASC-US)和低级别鳞状上皮内病变(LSIL)巴氏试验结果且感染某些HR-HPV基因型的女性发生高级别宫颈病变的风险非常低。HPV基因分型可以对这些HR-HPV阳性女性进行风险分层和分流优化。非典型腺细胞(AGC)巴氏试验结果的女性表现出特定的HPV基因分型模式,扩展的HPV基因分型可能有助于AGC的临床管理。将扩展基因分型纳入临床指南的持续进展将提高诊断准确性并完善临床管理策略。