Comprehensive overview of genotype distribution and prevalence of human papillomavirus in cervical lesions

Abstract

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.

Figure 1

HR-HPV genotyping for histologically negative cases and cervical squamous lesions. CIN, cervical intraepithelial neoplasia; HR-HPV, high-risk human papillomavirus; SCC, squamous cell carcinoma.

Figure 2

HR-HPV genotyping for histologically cervical glandular lesions. ADC, adenocarcinoma; ADSC, adenosquamous carcinoma; AIS, adenocarcinoma in situ; CIN, cervical intraepithelial neoplasia; HR-HPV, high-risk human papillomavirus; NEC, neuroendocrine carcinoma.

Figure 3

HR-HPV genotyping in women with ASC-US cytology. ASC-US, atypical squamous cells of undetermined significance; HR-HPV, high-risk human papillomavirus.

Figure 4

HR-HPV genotyping in women with LSIL cytology. HR-HPV, high-risk human papillomavirus; LSIL, low-grade squamous intraepithelial lesion.