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
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.
BACKGROUND Human papillomavirus (HPV) plays an important role in the development of cervical carcinoma. Although there is a general agreement that high levels of HPV are related to cervical cancer, the prevalence and distribution of HPV genotypes seems to vary by geographical region. This study was designed to investigate the prevalence of HPV genotypes in Gangwon Province, Korea. METHODS In total, 342 samples were examined by Pap smear and HPV-ID(R) reverse blot hybridization assay (REBA) (M&D, Wonju, Korea). RESULTS Overall HPV positivity was 80.9% and 64.4% in women with abnormal and normal cytology by REBA, respectively. The five most common HPV types were: HPV 16, 53, 58, 56, and 33 in samples with abnormal cytology, and HPV 16, 53, 58, 70, and 18 in samples with normal cytology. CONCLUSIONS The REBA can provide useful data regarding prevalence of HPV genotypes. Gangwon Province showed high prevalence of HPV infection in women. The most common HPV type in Gangwon Province was HPV16, and HPV 53, 58, 56, 70 were frequently present.
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