Background and precancerous diseases of the vulva and vagina: modern concepts, diagnostics, treatment and rehabilitation

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Abstract

The article is devoted to modern aspects of classification, epidemiology, pathogenesis, diagnostics, treatment and rehabilitation of background and precancerous diseases of the vulva and vagina. Particular attention is paid to stratification of intraepithelial neoplasia by HPV status, the role of immunohistochemical markers (p16, p53) and molecular genetic characteristics in prognostic assessment. Current data on clinical manifestations and diagnostic approaches, including non-invasive methods, reflective confocal microscopy are presented. Modern therapeutic strategies are summarized with an analysis of the effectiveness of imiquimod, photodynamic therapy, CO2 laser and surgical interventions. Approaches to multidisciplinary rehabilitation are described, including the use of vaginal dilators, pelvic floor physiotherapy, psychosexual support and telemedicine technologies. The emphasis is on the need for an interdisciplinary and personalized approach to the management of this category of patients in order to improve the quality of life and prevent malignancy.

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About the authors

A. G. Solopova

I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)

Author for correspondence.
Email: antoninasolopova@yandex.ru
ORCID iD: 0000-0002-7456-2386
SPIN-code: 5278-0465

Professor, MD

Russian Federation, Moscow

A. V. Vorobеv

I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)

Email: antoninasolopova@yandex.ru
ORCID iD: 0000-0002-4509-9281
SPIN-code: 5806-7062

Associate Professor, Candidate of Medical Science

 

Russian Federation, Moscow

J. Kh. Khizroeva

I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)

Email: antoninasolopova@yandex.ru
ORCID iD: 0000-0002-0725-9686
SPIN-code: 8225-4976

Professor, MD

Russian Federation, Moscow

A. E Ivanov

S.S. Yudin City Clinical Hospital, Moscow Healthcare Department

Email: antoninasolopova@yandex.ru
ORCID iD: 0000-0003-1115-3144

Candidate of Medical Science

Russian Federation, Moscow

D. O. Utkin

S.S. Yudin City Clinical Hospital, Moscow Healthcare Department

Email: antoninasolopova@yandex.ru
ORCID iD: 0000-0002-6620-2073
SPIN-code: 2368-7127

Candidate of Medical Science

Russian Federation, Moscow

O. S. Gridasova

R.T.H. Clinic

Email: antoninasolopova@yandex.ru
ORCID iD: 0009-0005-1775-9923
Russian Federation, Moscow

D. S. Tsarelunga

I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)

Email: antoninasolopova@yandex.ru
ORCID iD: 0009-0001-9930-4746
Russian Federation, Moscow

K. N. Grigoreva

I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)

Email: antoninasolopova@yandex.ru
ORCID iD: 0000-0002-7756-8935
SPIN-code: 6031-2462

Candidate of Medical Science

Russian Federation, Moscow

References

  1. Höhn A.K., Brambs C.E., Hiller G.G.R. et al. 2020 WHO Classification of Female Genital Tumors. Geburtshilfe Frauenheilkd. 2021; 81 (10): 1145–53. doi: 10.1055/a-1545-4279
  2. Parkash V., Aisagbonhi O., Riddle N. et al. Recent Advances in the Classification of Gynecological Tract Tumors: Updates From the 5th Edition of the World Health Organization "Blue Book". Arch Pathol Lab Med. 2023; 147 (10): 1204–16. doi: 10.5858/arpa.2022-0166-RA
  3. Watkins J., Fadare O. Precancerous Lesions of HPV-independent Vulvar Squamous Cell Carcinoma: Clinicopathologic Consideration of an Evolving Spectrum. Adv Anat Pathol. 2025; 32 (1): 4–19. doi: 10.1097/PAP.0000000000000472
  4. Agarossi A., Savasi V., Frangipane C. et al. High Risk of HPV-Related Preneoplastic and Neoplastic Vulvar Lesions in Women Living With HIV. J Low Genit Tract Dis. 2025; 29 (2): 118–22. doi: 10.1097/LGT.0000000000000864
  5. Cody P., Tobe K., Abe M. et al. Public health impact and cost effectiveness of routine and catch-up vaccination of girls and women with a nine-valent HPV vaccine in Japan: a model-based study. BMC Infect Dis. 2021; 21 (1): 11. doi: 10.1186/s12879-020-05632-0
  6. A D., Li J., Zhang D. et al. Status of common sexually transmitted infection in population referred for colposcopy and correlation with human papillomavirus infection. BMC Womens Health. 2023; 23 (1): 579. doi: 10.1186/s12905-023-02693-6
  7. Huang J., Yin C., Wang J. Relationship between vaginal microecological changes and oncogene E6/E7 and high-risk human papillomavirus infection. J Obstet Gynaecol. 2023; 43 (1): 2161349. doi: 10.1080/01443615.2022.2161349
  8. Zhao Y., Zhao L., Wang Z. et al. Clinical Performance of a Dedicated Urine-Based Assay for the Detection of Human Papillomavirus and Cervical Intraepithelial Neoplasia. Int J Womens Health. 2023; 15: 1909–16. doi: 10.2147/IJWH.S424621
  9. Мгерян А.Н., Назарова Н.М., Прилепская В.Н. Вульварная интраэпителиальная неоплазия, ассоциированная с ВПЧ-инфекцией: клинико-диагностические и лечебно-профилактические аспекты. Гинекология. 2023; 25 (3): 276–81 [Mgeryan A.N., Nazarova N.M., Prilepskaya V.N. Vulvar intraepithelial neoplasia associated with HPV infection: clinical, diagnostic, therapeutic and prophylactic aspects: A review. Gynecology. 2023; 25 (3): 276–81 (in Russ.)]. doi: 10.26442/20795696.2023.3.202296
  10. Thuijs N.B., van Beurden M., Bruggink A.H. et al. Vulvar intraepithelial neoplasia: Incidence and long-term risk of vulvar squamous cell carcinoma. Int J Cancer. 2021; 148 (1): 90–8. doi: 10.1002/ijc.33198
  11. Voss F.O., van Beurden M., Veelders K.J. et al. Incidence and Risk Factors for Recurrence and Progression of HPV-Independent Vulvar Intraepithelial Neoplasia. J Low Genit Tract Dis. 2024; 28 (2): 153–9. doi: 10.1097/LGT.0000000000000794
  12. Griesinger L.M., Walline H., Wang G.Y. et al. Expanding the Morphologic, Immunohistochemical, and HPV Genotypic Features of High-grade Squamous Intraepithelial Lesions of the Vulva With Morphology Mimicking Differentiated Vulvar Intraepithelial Neoplasia and/or Lichen Sclerosus. Int J Gynecol Pathol. 2021; 40 (3): 205–13. doi: 10.1097/PGP.0000000000000708
  13. Zhang J., Zhang Y., Zhang Z. Prevalence of human papillomavirus and its prognostic value in vulvar cancer: A systematic review and meta-analysis. PLoS One. 2018; 13 (9): e0204162. doi: 10.1371/journal.pone.0204162
  14. Lu M., Hong X., Liu T. et al. Clinical characteristics and risk factors to high-grade vaginal intraepithelial neoplasia: a single-institution study. BMC Womens Health. 2025; 25 (1): 44. doi: 10.1186/s12905-025-03585-7
  15. Зароченцева Н.В., Краснопольский В.И., Джиджихия Л.К. и др. Влагалищные интраэпителиальные неоплазии: диагностика, лечение, профилактика. Доктор.Ру. 2020; 19 (1): 44–50 [Zarochentseva N.V., Krasnopolsky V.I., Dzhidzhikhia L.K. et al. Vaginal Intraepithelial Neoplasia: Diagnostics, Treatment, and Prevention. Doctor.Ru. 2020; 19 (1): 44–50 (in Russ.)]. doi: 10.31550/1727-2378-2020-19-1-44-50
  16. Kim J.H., Kim J., Kim K. et al. Risk Factor and Treatment of Vaginal Intraepithelial Neoplasia After Hysterectomy for Cervical Intraepithelial Neoplasia. J Low Genit Tract Dis. 2022; 26 (2): 147–51. doi: 10.1097/LGT.0000000000000664
  17. Ампилогова Д.М., Солопова А.Г., Блинов Д.В. и др. Вульвовагинальная атрофия: проблемы лечения и реабилитации. Гинекология. 2022; 24 (4): 240–5 [Ampilogova D.M., Solopova A.G., Blinov D.V. et al. Vulvovaginal atrophy: issues of treatment and rehabilitation: A review. Gynecology. 2022; 24 (4): 240–5 (in Russ.)]. doi: 10.26442/20795696.2022.4.201792
  18. De Giorgi V., Magnaterra E., Zuccaro B. et al. Assessment of Vulvar Intraepithelial Neoplasia (VIN) Grades Based on Dermoscopic Features: A Diagnostic Study. Dermatol Pract Concept. 2023; 13 (4): e2023269. doi: 10.5826/dpc.1304a269
  19. Campaner A.B., Fernandes G.L. Discussion on cervical cytology in postmenopausal women. Minerva Obstet Gynecol. 2024; 76 (6): 532–9. doi: 10.23736/S2724-606X.23.05365-4
  20. Di Fiore R., Suleiman S., Drago-Ferrante R. et al. The Role of FBXW7 in Gynecologic Malignancies. Cells. 2023; 12 (10): 1415. doi: 10.3390/cells12101415
  21. Huisman B.W., Pagan L., Ulrich M. et al. Reflectance confocal microscopy as a non-invasive imaging tool in vulvar high-grade squamous intraepithelial lesions and lichen sclerosus: A descriptive morphological study in patients and healthy volunteers. Exp Dermatol. 2023; 32 (10): 1734–43. doi: 10.1111/exd.14888
  22. Cadman L., Reuter C., Jitlal M. et al. A Randomized Comparison of Different Vaginal Self-sampling Devices and Urine for Human Papillomavirus Testing-Predictors 5.1. Cancer Epidemiol Biomarkers Prev. 2021; 30 (4): 661–8. doi: 10.1158/1055-9965.EPI-20-1226
  23. Milanova V., Lazarova I., Mihaylova K. et al. Efficacy and acceptability of a self-collected medical grade tampon as a novel vaginal sample collection tool for the detection of HPV and STIs. BMC Womens Health. 2025; 25 (1): 141. doi: 10.1186/s12905-025-03652-z
  24. Nappi R.E., Martini E., Cucinella L. et al. Addressing Vulvovaginal Atrophy (VVA)/Genitourinary Syndrome of Menopause (GSM) for Healthy Aging in Women. Front Endocrinol (Lausanne). 2019; 10: 561. doi: 10.3389/fendo.2019.00561
  25. Lebreton M., Carton I., Brousse S. et al. Vulvar intraepithelial neoplasia: Classification, epidemiology, diagnosis, and management. J Gynecol Obstet Hum Reprod. 2020; 49 (9): 101801. doi: 10.1016/j.jogoh.2020.101801
  26. Vieira-Baptista P., Pérez-López F.R., López-Baena M.T. et al. Risk of Development of Vulvar Cancer in Women With Lichen Sclerosus or Lichen Planus: A Systematic Review. J Low Genit Tract Dis. 2022; 26 (3): 250–7. doi: 10.1097/LGT.0000000000000673
  27. Halonen P., Jakobsson M., Heikinheimo O. et al. Lichen sclerosus and risk of cancer. Int J Cancer. 2017; 140 (9): 1998–2002. doi: 10.1002/ijc.30621
  28. Singh N., Ghatage P. Etiology, Clinical Features, and Diagnosis of Vulvar Lichen Sclerosus: A Scoping Review. Obstet Gynecol Int. 2020; 2020: 7480754. doi: 10.1155/2020/7480754
  29. Grosu-Bularda A., Hariga C.S., Dumitru C.S. et al. Clinicopathological Findings and Comprehensive Review of Buschke-Lowenstein Tumors Based on a Case Study. J Pers Med. 2024; 14 (8): 887. doi: 10.3390/jpm14080887
  30. Sato H., Murakami K., Otani T. et al. Tubulovillous adenoma with high-grade dysplasia of the vulva harboring high tumor mutational burden and cancer-associated mutations: a case report. Diagn Pathol. 2022; 17 (1): 85. doi: 10.1186/s13000-022-01268-7
  31. Оразов М.Р., Силантьева Е.С., Радзинский В.Е. и др. Вульвовагинальная атрофия в пери- и постменопаузе: актуальность проблемы и влияние на качество жизни. Гинекология. 2022; 24 (5): 408–12 [Orazov M.R., Silantyeva E.S., Radzinsky V.E. et al. Vulvovaginal atrophy in the peri- and post-menopause: relevance and impact on quality of life. Gynecology. 2022; 24 (5): 408–12 (in Russ.)]. doi: 10.26442/20795696.2022.5.201854
  32. Guillon S., Cavadias I., Brun P. et al. Lésions vulvaires précancéreuses: mise au point [Update on precursors of vulvar carcinoma]. Gynecol Obstet Fertil Senol. 2021; 49 (6): 538–46 (in French). doi: 10.1016/j.gofs.2020.11.002. Epub 2020 Nov 6. Erratum in: Gynecol Obstet Fertil Senol. 2021; 49 (6): 567. doi: 10.1016/j.gofs.2021.03.022
  33. Simon J.A., Ferenczy A., Black D. et al. Efficacy, tolerability, and endometrial safety of ospemifene compared with current therapies for the treatment of vulvovaginal atrophy: a systematic literature review and network meta-analysis. Menopause. 2023; 30 (8): 855–66. doi: 10.1097/GME.0000000000002211
  34. Inayama Y., Yamanishi Y., Nakatani E. et al. Imiquimod for vaginal intraepithelial neoplasia 2-3: A systematic review and meta-analysis. Gynecol Oncol. 2021; 160 (1): 140–7. doi: 10.1016/j.ygyno.2020.09.031
  35. Han Q., Wu Z., Guo H. et al. Efficacy and safety of photodynamic therapy mediatied by 5-aminolevulinic acid for the treatment of vaginal high-grade intraepithelial lesions. Photodiagnosis Photodyn Ther. 2022; 39: 102899. doi: 10.1016/j.pdpdt.2022.102899
  36. Freitas G., Costa A. Non-Excisional therapeutic modalities in vaginal intraepithelial neoplasia. Eur J Obstet Gynecol Reprod Biol. 2023; 284: 175–9. doi: 10.1016/j.ejogrb.2023.03.014
  37. Bizoń M., Maślińska D., Sawicki W. Influence of Photodynamic Therapy on Lichen Sclerosus with Neoplastic Background. J Clin Med. 2022; 11 (4): 1100. doi: 10.3390/jcm11041100
  38. D'Oria O., Giannini A., Buzzaccarini G. et al. Fractional Co2 laser for vulvo-vaginal atrophy in gynecologic cancer patients: A valid therapeutic choice? A systematic review. Eur J Obstet Gynecol Reprod Biol. 2022; 277: 84–9. doi: 10.1016/j.ejogrb.2022.08.012
  39. Lami A., Alvisi S., Baldassarre M. et al. Safety and efficacy of non-ablative CO2 laser treatment of vulvo-vaginal atrophy in women with history of breast cancer. Arch Gynecol Obstet. 2024; 309 (4): 1575–83. doi: 10.1007/s00404-023-07323-y
  40. 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. Int J Gynecol Cancer. 2023; 33 (4): 446–61. doi: 10.1136/ijgc-2022-004213
  41. Singh N., Mishra N., Ghatage P. Treatment Options in Vulvar Lichen Sclerosus: A Scoping Review. Cureus. 2021; 13 (2): e13527. doi: 10.7759/cureus.13527
  42. Medeiros A.G., Cintra M.M.M., Dos Reis M.A. et al. The effects of various therapies on vulvovaginal atrophy and quality of life in gynecological cancer patients: a systematic review. Arch Gynecol Obstet. 2024; 310 (2): 631–41. doi: 10.1007/s00404-024-07552-9
  43. Di Donato V., Caruso G., Bogani G. et al. HPV Vaccination after Primary Treatment of HPV-Related Disease across Different Organ Sites: A Multidisciplinary Comprehensive Review and Meta-Analysis. Vaccines (Basel). 2022; 10 (2): 239. doi: 10.3390/vaccines10020239
  44. Pérez-López F.R., Phillips N., Vieira-Baptista P. et al. Management of postmenopausal vulvovaginal atrophy: recommendations of the International Society for the Study of Vulvovaginal Disease. Gynecol Endocrinol. 2021; 37 (8): 746–52. doi: 10.1080/09513590.2021.1943346
  45. Kagan R., Kellogg-Spadt S., Parish S.J. Practical Treatment Considerations in the Management of Genitourinary Syndrome of Menopause. Drugs Aging. 2019; 36 (10): 897–908. doi: 10.1007/s40266-019-00700-w
  46. Sayer-Jones K., Sherman K.A. Body image concerns in individuals diagnosed with benign gynaecological conditions: scoping review and meta-synthesis. Health Psychol Behav Med. 2021; 9 (1): 456–79. doi: 10.1080/21642850.2021.1920949
  47. Nappi R.E., Guida M., Marchesoni D. et al. Investigators of the EVES Study. Vulvovaginal atrophy of menopause and its impact on sexual function in an Italian clinical cohort of post-menopausal women. J Obstet Gynaecol. 2021; 41 (2): 290–7. doi: 10.1080/01443615.2020.1832973
  48. Liu M., Juravic M., Mazza G. et al. Vaginal Dilators: Issues and Answers. Sex Med Rev. 2021; 9 (2): 212–20. doi: 10.1016/j.sxmr.2019.11.005
  49. arter J., Goldfarb S., Baser R.E. et al. A single-arm clinical trial investigating the effectiveness of a non-hormonal, hyaluronic acid-based vaginal moisturizer in endometrial cancer survivors. Gynecol Oncol. 2020; 158 (2): 366–74. doi: 10.1016/j.ygyno.2020.05.025
  50. Hill D.A., Taylor C.A. Dyspareunia in Women. Am Fam Physician. 2021; 103 (10): 597–604.
  51. Yang D., Li J., Yang Y. et al. Application of Perioperative Pain Management in the Perioperative Nursing of Labia Minora Plasty and its Effect on the Rehabilitation of Patients. Altern Ther Health Med. 2024; 30 (4): 118–23.
  52. Charatsi D., Vanakara P., Evaggelopoulou E. et al. Vaginal dilator use to promote sexual wellbeing after radiotherapy in gynecological cancer survivors. Medicine (Baltimore). 2022; 101 (4): e28705. doi: 10.1097/MD.0000000000028705
  53. Cyr M.P., Dostie R., Camden C. et al. Improvements following multimodal pelvic floor physical therapy in gynecological cancer survivors suffering from pain during sexual intercourse: Results from a one-year follow-up mixed-method study. PLoS One. 2022; 17 (1): e0262844. doi: 10.1371/journal.pone.0262844
  54. Suvaal I., Kirchheiner K., Nout R.A. et al. Vaginal changes, sexual functioning and distress of women with locally advanced cervical cancer treated in the EMBRACE vaginal morbidity substudy. Gynecol Oncol. 2023; 170: 123–32. doi: 10.1016/j.ygyno.2023.01.005
  55. Jamieson A., Tse S.S., Proctor L. et al. A Scoping Review of Treatment Outcome Measures for Vulvar Intraepithelial Neoplasia. J Low Genit Tract Dis. 2022; 26 (4): 328–38. doi: 10.1097/LGT.0000000000000698
  56. Sirotkina M.A., Potapov A.L., Loginova M.M. et al. Evaluation of Skin Recovery after Fractional CO2 Laser Treatment Lichen Sclerosus Using Multimodal Optical Coherence Tomography. Sovrem Tekhnologii Med. 2024; 16 (4): 15–26. doi: 10.17691/stm2024.16.4.02
  57. Millman R., Jacox N., Sears C. et al. Patient interest in the Lowdown on Down There: attendance at a vulvovaginal and sexual health workshop post-cancer treatment. Support Care Cancer. 2020; 28 (8): 3889–96. doi: 10.1007/s00520-019-05162-9
  58. Nascimento F.C., Sampaio I.M., Nunes G.S. et al. A physical therapy program to treat late-effect vaginal stenosis in gynecological cancer survivors: An interventional study. Support Care Cancer. 2024; 32 (12): 839. doi: 10.1007/s00520-024-09053-6
  59. Coad B., Ramani S., Michel L. et al. Effectiveness of telehealth physical therapy for patients with pelvic floor disorders in a community hospital setting. Arch Gynecol Obstet. 2023; 308 (2): 661–5. doi: 10.1007/s00404-023-07078-6
  60. Cyr M.P., Jones T., Brennen R. et al. Effectiveness of Pelvic Floor Muscle and Education-Based Therapies on Bladder, Bowel, Vaginal, Sexual, Psychological Function, Quality of Life, and Pelvic Floor Muscle Function in Females Treated for Gynecological Cancer: A Systematic Review. Curr Oncol Rep. 2024; 26 (11): 1293–320. doi: 10.1007/s11912-024-01586-7

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