Diagnostic value of cytology in detecting human papillomavirus–independent cervical malignancies: a nation-wide study in Korea
Year: 2025
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Human papillomavirus (HPV) independent cervical malignancies (HPV-IDCMs) have recently been classified by the World Health Organization (WHO) 5th edition. These malignancies have historically received limited attention due to their rarity and the potential for evasion of HPV-based screening. METHODS: We retrospectively reviewed 5,854 biopsy-confirmed cervical malignancies from 22 institutions over 3 years (July 2020-June 2023). Histologic classification followed the WHO guidelines. HPV independence was confirmed by dual negativity for p16 and HPV; discordant cases (p16-positive/HPV-negative) underwent additional HPV testing using paraffin-embedded tissue. Cytological results were matched sequentially to histological confirmation. RESULTS: The prevalence of HPV-IDCM was 4.4% (257/5,854) overall and was 3.6% (208/5,805 cases) among primary cervical malignancy. Patient age of HPV-IDCM was 29 to 89 years (median, 57.79). Its histologic subtypes included primary adenocarcinoma (n = 116), endometrial adenocarcinoma (n = 35), squamous cell carcinoma (n = 72), metastatic carcinoma (n = 14), carcinoma, not otherwise specified (n = 10), neuroendocrine carcinoma (n = 3), and others (n = 7). Among 155 cytology-histological matched cases, the overall and primary Pap test detection rates were 85.2% (132/155) and 83.2% (104/125), respectively. The interval between cytology and histologic confirmation extended up to 38 months. CONCLUSIONS: HPV-IDCMs comprised 3.6% of primary cervical malignancies with a high detection rate via cytology (83.2%). These findings affirm the value of cytological screening, particularly in patients with limited screening history or at risk for HPV-independent lesions, and may guide future screening protocols.
Authors: Hye-Ra Jung, Junyoung Shin, Chong Woo Yoo, Eun Na Kim, Cheol Lee, Kyeongmin Kim, Ho-chang Lee, Yonghee Lee, Ji Hye Kim, Soo Jin Jung, Yumin Chung, Joo Yeon Kim, Hye Eun Park, Tae Hoen Kim, Wonae Lee, Min-Sun Cho, Ran Hong, Yoon Jung Choi, Younghee Choi, Young Sub Lee, Sang-Ryung Lee, Myunghee Kang, Young Jin Seo, Seung-Sook Lee, Yoon-Jung Hwang, Hyun-Jung Kim
Institutions: Keimyung University, National Cancer Center, Seoul National University, Seoul National University Hospital, Soonchunhyang University, Soonchunhyang University Hospital Seoul, Chungbuk National University, Chungbuk National University Hospital, Ajou University, Catholic University of Korea, University of Ulsan, Inje University Haeundae Paik Hospital, Inje University Busan Paik Hospital, Kangbuk Samsung Hospital, Sungkyunkwan University, Seoul Metropolitan Government, CHA University Bundang Medical Center, CHA University, Dankook University Hospital, Ewha Womans University, Ewha Womans University Medical Center, Chosun University Hospital, Yonsei University, Hallym University Dongtan Sacred Heart Hospital, Yongin Severance Hospital, CHA University Gangnam Medical Center, Gachon University Gil Medical Center, National Forensic Institute, Seoul National University Bundang Hospital, Inje University Sanggye Paik Hospital
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $175
Funders: Seoul National University Bundang Hospital, Chosun University, Dankook University, Seoul National University, Yonsei University, Ewha Womans University, Gachon University, Hallym University, Inje University, Sungkyunkwan University, CHA University, Samsung, Yonsei University College of Medicine, College of Medicine, Catholic University of Korea
OpenAlex ID: W4416137290