Research Progress on the Correlation between Human Papilloma Virus and Vaginal Intraepithelial Neoplasia/Vaginal Cancer

doi:10.12280/gjfckx.20260156

Abstract

Abstract:

Human papilloma virus (HPV) infection is a significant causative factor for lower female genital tract lesions. Persistent infection with high-risk HPV types is closely associated with the development and progression of vaginal intraepithelial neoplasia (VaIN) and vaginal cancer, particularly vaginal squamous cell carcinoma. As VaIN lacks typical clinical symptoms and is highly occult, VaIN2/3 represents a vaginal precancerous lesion prone to missed diagnosis in clinical practice. In recent years, with the standardized application of HPV testing and colposcopy in cervical cancer screening, the detection rates of early-stage vaginal cancer and VaIN have also significantly increased. This review systematically outlines recent clinical research progress on the correlation between HPV and VaIN as well as vaginal cancer, aiming to provide a reference for formulating clinical prevention and management strategies for these lesions.

Key words: Squamous intraepithelial lesions, Vaginal neoplasms, Papillomavirus vaccines, Human papilloma virus, Vaginal intraepithelial neoplasia

GUO Chen-yao, WANG Zhi-lian. Research Progress on the Correlation between Human Papilloma Virus and Vaginal Intraepithelial Neoplasia/Vaginal Cancer[J]. Journal of International Obstetrics and Gynecology, 2026, 53(4): 385-389.

References 37

[1]	中华预防医学会肿瘤预防与控制专业委员会, 中华预防医学会疫苗与免疫分会. 人乳头瘤病毒相关的非宫颈疾病早期预防专家共识(2025版)[J]. 中华医学杂志, 2025, 105(30):2536-2550. doi: 10.3760/cma.j.cn112137-20250519-01212.
[2]	Adams TS, Maluleke JC, Cuello MA. Cancer of the vagina: 2025 update[J]. Int J Gynaecol Obstet, 2025, 171(Suppl 1):48-59. doi: 10.1002/ijgo.70325.
[3]	Kesic V, Carcopino X, Preti M, et al. The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) consensus statement on the management of vaginal intraepithelial neoplasia[J]. Int J Gynecol Cancer, 2023, 33(4):446-461. doi: 10.1136/ijgc-2022-004213. pmid: 36958755
[4]	Cree IA, White VA, Indave BI, et al. Revising the WHO classification: female genital tract tumours[J]. Histopathology, 2020, 76(1):151-156. doi: 10.1111/his.13977. pmid: 31846528
[5]	Indraccolo U, Borghi C, Gentili MM, et al. Natural History of Primary Vaginal Intraepithelial Neoplasia With and Without Treatment: A Systematic Review and Meta-Analysis[J]. Clin Exp Obstet Gynecol, 2025, 52(8):1. doi: 10.31083/ceog36377.
[6]	Wei J, Wu Y. Comprehensive evaluation of vaginal intraepithelial neoplasia development after hysterectomy: insights into diagnosis and treatment strategies[J]. Arch Gynecol Obstet, 2024, 310(1):1-10. doi: 10.1007/s00404-024-07530-1. pmid: 38743076
[7]	张丽丽, 唐雪丽, 耿莉, 等. 子宫切除术后患者阴道残端人乳头瘤病毒基因型分析及其对阴道残端上皮细胞的影响[J]. 中国实用妇科与产科杂志, 2025, 41(10):1027-1030. doi: 10.19538/j.fk2025100114.
[8]	中国优生科学协会女性生殖道疾病分会, 中国优生科学协会肿瘤生殖学分会, 中国医院协会妇产医院分会妇科肿瘤专业学组, 等. 阴道上皮内瘤变诊治中国专家共识(2024年版)[J]. 中国实用妇科与产科杂志, 2024, 40(12):1226-1234. doi: 10.19538/j.fk2024120115.
[9]	Stuebs FA, Dietl AK, Koch MC, et al. Cytology and HPV Co-Testing for Detection of Vaginal Intraepithelial Neoplasia: A Retrospective Study[J]. Cancers(Basel), 2023, 15(18):4633. doi: 10.3390/cancers15184633.
[10]	Suchońska B, Ługowski F, Papież M, et al. Vaginal Intraepithelial Neoplasia (VaIN)-A Retrospective Cohort Analysis of Epidemiology, Risk Factors, and Management in an Academic Clinical Center[J]. J Clin Med, 2025, 14(15):5386. doi: 10.3390/jcm14155386.
[11]	Preti M, Boldorini R, Gallio N, et al. Human papillomavirus genotyping in high-grade vaginal intraepithelial neoplasia: A multicentric Italian study[J]. J Med Virol, 2024, 96(2):e29474. doi: 10.1002/jmv.29474.
[12]	Lu M, Hong X, Liu T, et al. Clinical characteristics and risk factors to high-grade vaginal intraepithelial neoplasia: a single-institution study[J]. BMC Womens Health, 2025, 25(1):44. doi: 10.1186/s12905-025-03585-7. pmid: 39893434
[13]	Ao M, Zheng D, Wang J, et al. A retrospective study of cytology and HPV genotypes results of 3229 vaginal intraepithelial neoplasia patients[J]. J Med Virol, 2022, 94(2):737-744. doi: 10.1002/jmv.27311.
[14]	Ye Y, Li M, Yang W, et al. Characteristics of high-risk HPV infection in women with vaginal intraepithelial neoplasia in Beijing, China[J]. J Med Virol, 2023, 95(12):e29267. doi: 10.1002/jmv.29267.
[15]	Bertoli HK, Rasmussen CL, Sand FL, et al. Human papillomavirus and p16 in squamous cell carcinoma and intraepithelial neoplasia of the vagina[J]. Int J Cancer, 2019, 145(1):78-86. doi: 10.1002/ijc.32078. pmid: 30561092
[16]	Sinno AK, Saraiya M, Thompson TD, et al. Human papillomavirus genotype prevalence in invasive vaginal cancer from a registry-based population[J]. Obstet Gynecol, 2014, 123(4):817-821. doi: 10.1097/AOG.0000000000000171. pmid: 24785610
[17]	Zhao X, Wang H, Hong Y, et al. Clinical characteristics, treatment patterns, and prognosis in vulvar cancer and vaginal cancer: a national multicenter retrospective study in China[J]. BMC Public Health, 2026, 26(1):1831. doi: 10.1186/s12889-026-27384-3.
[18]	Bruno MT, Panella MM, Valenti G, et al. Vaginal Intraepithelial Neoplasia (VaIN) after Hysterectomy Is Strongly Associated with Persistent HR-HPV Infection[J]. Cancers(Basel), 2024, 16(14):2524. doi: 10.3390/cancers16142524.
[19]	de Groen PC. The strength of organ, tissue, and body field effects determines the frequency of all neoplasia[J]. Ann N Y Acad Sci, 2025, 1546(1):11-22. doi: 10.1111/nyas.15306.
[20]	Zhang S, Saito M, Yamada S, et al. The prevalence of VAIN, CIN, and related HPV genotypes in Japanese women with abnormal cytology[J]. J Med Virol, 2020, 92(3):364-371. doi: 10.1002/jmv.25611. pmid: 31642536
[21]	Wang M, Liang H, Yan Y, et al. Distribution of HPV types among women with HPV-related diseases and exploration of lineages and variants of HPV 52 and 58 among HPV-infected patients in China: A systematic literature review[J]. Hum Vaccin Immunother, 2024, 20(1):2343192. doi: 10.1080/21645515.2024.2343192.
[22]	Shen Y, Tang S, Zhou Y, et al. Human Papillomavirus Genotype Attribution and Integration in High-Grade Vaginal Intraepithelial Neoplasia[J]. J Low Genit Tract Dis, 2025, 29(1):60-67. doi: 10.1097/LGT.0000000000000850. pmid: 39620892
[23]	Williams GA, Wu AA, Eugene HC, et al. Clinicopathologic Features and Viral Status of Low-risk HPV6 and HPV11-Associated Squamous Cell Carcinoma of the Uterine Cervix and Vulva[J]. Am J Surg Pathol, 2025, 49(5):458-470. doi: 10.1097/PAS.0000000000002367.
[24]	Zhou D, Xue J, Sun Y, et al. Patterns of single and multiple HPV infections in female: A systematic review and meta-analysis[J]. Heliyon, 2024, 10(17):e35736. doi: 10.1016/j.heliyon.2024.e35736.
[25]	Chen Y, Chen Q, Xue H, et al. Clinical Characteristics and Detection Sensitivity of Cervical Cancer Screening in Vaginal Intraepithelial Neoplasia[J]. J Low Genit Tract Dis, 2024, 28(2):137-142. doi: 10.1097/LGT.0000000000000793. pmid: 38109483
[26]	Shi X, Lian J, Yang Y, et al. Human Papillomavirus-Associated Risk Factors and Clinical Characteristics of Vaginal Intraepithelial Neoplasia: A Retrospective Study[J]. J Med Virol, 2026, 98(1):e70766. doi: 10.1002/jmv.70766.
[27]	Calvin Devadasan JD, Nithyanandhan K, Fletcher GJ, et al. HPV vaccines-A game changer for preventing HPV-related cancers[J]. Indian J Med Microbiol, 2025, 55:100847. doi: 10.1016/j.ijmmb.2025.100847.
[28]	Kiamba EW, Goodier MR, Clarke E. Immune responses to human papillomavirus infection and vaccination[J]. Front Immunol, 2025, 16:1591297. doi: 10.3389/fimmu.2025.1591297.
[29]	中华医学会妇科肿瘤学分会, 中国优生科学协会阴道镜和宫颈病理学分会, 中华预防医学会肿瘤预防与控制专委会, 等. 预防性人乳头瘤病毒疫苗中国临床应用指南(2025版)[J]. 现代妇产科进展, 2025, 34(3):166-177. doi: 10.13283/j.cnki.xdfckjz.2025.03.002.
[30]	Falkenthal T, Nygård S, Nygård M. Beyond Women's Health: Long-Term Human Papillomavirus-Related Cancer Trends in Norway[J]. J Infect Dis, 2025, 232(6):e897-e905. doi: 10.1093/infdis/jiaf351.
[31]	Montero-Macías R, Adam M, Rouzier R, et al. HPV vaccination efficacy in primary and tertiary prevention of vulvar and vaginal HPV-related high grade dysplasia and cancers: A systematic review[J]. Hum Vaccin Immunother, 2025, 21(1):2567704. doi: 10.1080/21645515.2025.2567704.
[32]	Bertoli HK, Baandrup L, Aalborg GL, et al. Time trends in the incidence and survival of vaginal squamous cell carcinoma and high-grade vaginal intraepithelial neoplasia in Denmark-A nationwide population-based study[J]. Gynecol Oncol, 2020, 158(3):734-739. doi: 10.1016/j.ygyno.2020.05.683.
[33]	Deng Y, Wu S, Ask LS, et al. Quadrivalent Human Papillomavirus Vaccine and High-Grade Vulvovaginal Lesions[J]. JAMA Oncol, 2026, 12(2):177-184. doi: 10.1001/jamaoncol.2025.5511.
[34]	潘程浩, 由婷婷, 谢佳鑫, 等. 预防性人乳头瘤病毒疫苗的应用及卫生经济学评价研究进展[J]. 中国病毒病杂志, 2025, 15(2):199-204. doi: 10.16505/j.2095-0136.2025.0011.
[35]	Islam MR, Rauf A, Aktar MN, et al. Recent advances in human papillomavirus vaccines and therapeutic strategies: Combating cervical and non-cervical cancers[J]. Genes Dis, 2026, 13(3):101880. doi: 10.1016/j.gendis.2025.101880.
[36]	Martín E, Reina G, Carlos S. Advances in Therapeutic Vaccines Against HPV: A Review of Human Clinical Trials[J]. Curr Oncol, 2025, 32(11):600. doi: 10.3390/curroncol32110600.
[37]	Eerkens AL, Esajas MD, Brummel K, et al. Vvax001, a Therapeutic Vaccine, for Patients with HPV16-Positive High-grade Cervical Intraepithelial Neoplasia: A Phase II Trial[J]. Clin Cancer Res, 2025, 31(6):1016-1026. doi: 10.1158/1078-0432.CCR-24-1662.