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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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AbstractAbstract 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.
Human Papillomavirus Prevalence in Gangwon Province Using Reverse Blot Hybridization Assay.
Dongsup Lee, Sunghyun Kim, Sangjung Park, Hyunwoo Jin, Tae Ue Kim, Kwang Hwa Park, Hyeyoung Lee
Korean J Pathol. 2011;45(4):348-353.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.4.348
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  • 6 Crossref
AbstractAbstract PDF
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.

Citations

Citations to this article as recorded by  
  • Human Papillomavirus (HPV69/HPV73) Coinfection associated with Simultaneous Squamous Cell Carcinoma of the Anus and Presumed Lung Metastasis
    Stephanie Shea, Marina Muñoz, Stephen C. Ward, Mary B. Beasley, Melissa R Gitman, Michael D Nowak, Jane Houldsworth, Emilia Mia Sordillo, Juan David Ramirez, Alberto E. Paniz Mondolfi
    Viruses.2020; 12(3): 349.     CrossRef
  • Distribution of Oncogenic Human Papillomavirus Genotypes at High Grade Cervical Lesions above CIN 2 Grade with Histological Diagnosis
    Geehyuk Kim, Sungyoung Park, Hye-young Wang, Sunghyun Kim, Sangjung Park, Kwangmin Yu, Boohyung Lee, Seung-Ju Ahn, Eun-Joong Kim, Dongsup Lee
    Biomedical Science Letters.2016; 22(2): 37.     CrossRef
  • Human Papillomavirus Prevalence and Distribution according to Age among Korean and Chinese Women
    Geehyuk Kim, Sunghyun Kim, Sunyoung Park, Sangjung Park, Han Lin, Yubo Ren, Li Yingxue, In Soo Lee, Jae Dal Lee, Dongsup Lee
    Korean Journal of Clinical Laboratory Science.2015; 47(4): 259.     CrossRef
  • Comparison of Methods for Measuring Histamine by ELISA and HPLC-MS Assay In Vitro
    In Hee Lee, Yoo Hyun Kim
    Korean Journal of Clinical Laboratory Science.2015; 47(4): 306.     CrossRef
  • Diagnostic Performance of HPV E6/E7 mRNA and HPV DNA Assays for the Detection and Screening of Oncogenic Human Papillomavirus Infection among Woman with Cervical Lesions in China
    Hye-young Wang, Dongsup Lee, Sunyoung Park, Geehyuk Kim, Sunghyun Kim, Lin Han, Ren Yubo, Yingxue Li, Kwang Hwa Park, Hyeyoung Lee
    Asian Pacific Journal of Cancer Prevention.2015; 16(17): 7633.     CrossRef
  • Uncommon and Rare Human Papillomavirus Genotypes Relating to Cervical Carcinomas
    Na Rae Kim, Myunghee Kang, Soon Pyo Lee, Hyunchul Kim, Jungsuk An, Dong Hae Chung, Seung Yeon Ha, Hyun Yee Cho
    Korean Journal of Pathology.2014; 48(1): 43.     CrossRef

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