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Original Article
- Diagnostic value of cytology in detecting human papillomavirus–independent cervical malignancies: a nation-wide study in Korea
- 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
- J Pathol Transl Med. 2025;59(6):444-452. Published online November 11, 2025
- DOI: https://doi.org/10.4132/jptm.2025.10.21
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Abstract
PDF - 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.
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