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Research Article: Prevalence and genotype distribution of human papillomavirus in cervical cancer and precancer in Japan between 2012 and 2025: a retrospective single-center study

Date Published: 2026-06-12

Abstract:
This study aimed to provide the latest data on the distribution of human papillomavirus (HPV) genotypes in cervical cancer and precancer at a single university hospital in Tokyo, Japan, between 2012 and 2025. Cervical exfoliated cell specimens collected from 2,536 women with histologically confirmed, cervical intraepithelial neoplasia 2 (CIN2), CIN3, squamous cell carcinoma (SCC), adenocarcinoma in situ (AIS), adenosquamous cell carcinoma (ASC), and adenocarcinoma (ADC), were tested by HPV L1 PCR followed by reverse blot hybridization for HPV genotyping. Overall, HPV positivity was 96.6%, with high detection rates in CIN2 (98.5%), CIN3 (98.2%), and SCC (96.1%), and slightly lower rates in ADC (78.3%). In squamous lesions, HPV16 infections were the most prevalent and increased progressively with lesion severity (33.2% in CIN2, 50.1% in CIN3, 61.7% in SCC). Prevalence ratio analysis demonstrated a significantly higher prevalence of HPV16 in CIN3 versus CIN2 and in SCC versus CIN3, supporting its strong association with progression to invasive cancer. In contrast, HPV52 and HPV58 infections decreased with disease progression. In glandular lesions, HPV16 and HPV18 predominated across AIS, ASC, and ADC. Among ADC subtypes, usual-type ADC showed the highest HPV positivity (89.8%), whereas endometrioid, minimal deviation, serous, and clear-cell subtypes showed low or absent HPV positivity, highlighting the etiologic heterogeneity of ADC. Among single-type infection cases, the proportion of lesions attributable to vaccine-preventable types (HPV16/18) increased with severity in squamous lesions (31.9% in CIN2 to 72.2% in SCC) and remained consistently high in glandular lesions (>94%). Regarding HPV16/18/31/33/45/52/58, potential coverage exceeded 87% in CIN2 and 92% in SCC. These findings confirm the central role of HPV16 in cervical carcinogenesis, and highlight the contribution of HPV52 and HPV58 in precancerous lesions, which further underscores the need for the widespread adoption of the nonavalent vaccine in Japan.

Introduction:
Cervical cancer ranks fourth worldwide in both cancer morbidity and mortality, primarily caused by persistent infection with oncogenic human papillomavirus (HPV) ( 1 ). Of more than 400 HPV genotypes identified to date (The Papillomavirus Episteme, https://pave.niaid.nih.gov/ ), about 15 types (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82) are defined as “high-risk” types ( 2 ), because they are frequently detected in invasive cervical cancer and its precancerous lesions ( 3 , 4 ). Worldwide,…

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