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8/1/2018

Vaginal Squamous Intraepithelial Lesions

Vaginal intraepithelial neoplasia (VaIN) affects 0.2 per 100,000 women in the United States.  VaIN, like cervical intraepithelial neoplasia (CIN), is caused by human papillomavirus (HPV).  High-risk HPV (hrHPV) positivity has been reported in 99% of VaIN 1 and 90-96% of VaIN 2/3 lesions.  As in other HPV-mediated lower genital tract neoplasias, VaIN 1 represents a transient, productive viral infection.  By comparison, VaIN 2/3 lesions are truly precancerous.  These high-grade neoplasias represent lesions where HPV has disrupted the cell cycle causing proliferation of undifferentiated cells that if persistent carry a significant risk of malignant transformation. 

Transient viral lesions (VaIN 1) are termed vaginal low grade squamous intraepithelial lesions (LSIL) and precancerous lesions (VaIN 2/3) are termed vaginal high grade squamous intraepithelial lesions (HSIL).

There are no recommendations to screen low risk individuals for VaIN. Individuals who have had a hysterectomy for benign conditions with no prior history of HSIL do not require further screening. Individuals with a history of cervical pre cancer (CIN 2 and/or CIN 3) or cervical cancer who are post hysterectomy should be screened be screened with vaginal cytology for at least 20 years after treatment.

Current management recommendations rely on expert opinion and retrospective studies. Those with HSIL, atypical squamous cells, cannot rule out high grade (ASC-H), or atypical glandular cells on vaginal cytology should undergo vaginal colposcopy. Individuals with vaginal atypical cells of underdetermined significance (ASCUS) or LSIL should not undergo immediate treatment and should be managed expectantly.  After a single ASCUS/LSIL cytologic result or cytology negative/HPV positive cotest, individuals should be rescreened in 1 year with either cytology alone or co-testing. If HPV genotyping is performed, however, and HPV 16/18 is positive, immediate colposcopy is recommended. If cytology is persistently abnormal for two years, or co-testing abnormal one year later, vaginal colposcopy is recommended.  At subsequent follow-up exams if an individual  has one negative co-test or two negative cytology, routine surveillance is recommended.   Individuals with persistent and stable LSIL beyond 2 years can have their follow-up interval extended to every 2-3 years.   Women with persistent LSIL beyond 2 years may also undergo treatment as an acceptable alternative.     

Any woman with VAIN 2/3 should be treated given its malignant potential.  Treatment can include excision, ablation, medical or brachytherapy. Treatment decisions should be individualized based on a woman’s prior treatment, the presence of multifocal disease, other medical co-morbidities, and desire to preserve sexual function. Invasive disease must be excluded prior to medical, ablative or brachytherapies. Ablative therapies include CO2 laser  vaporization, photodynamic therapy and plasma energy ablation.  Disadvantages of ablative therapies include the risk of missing an invasive cancer. These therapies are well tolerated with low incidences of postoperative pain or scarring.  The most common topical therapies include 5% imiquimod, 5-fluorouracil or trichloroacetic acid.  Side effects of topical therapies include local burning and soreness that does not result in treatment disruption or interfere with usual activities. A disadvantage of topical vaginal creams is they cannot reach buried epithelium in the vaginal cuff scar. Excisional treatments must preceded by pre-operative colposcopic assessment of the vagina to ensure adequate excision. They are associated with higher risks of sexual dysfunction, persistent pain, and scarring that can be attributed to the shortening or stenosis of vagina. Brachytherapy is not usually proposed as a first-line therapy because of  the risks of radiation. Following treatment, women require long term follow-up with annual cytologic screening or every 2-3 years co-testing, once initial follow-up is negative. Referral to a gynecologic oncologist is recommended for large or complex lesions.

Further reading:

Khan MJ, Massad LS, Kinney W, et al.  A common clinical dilemma: Management of abnormal vaginal cytology and human papillomavirus test results.  Gynecol Oncol. 2016 May;141(2):364-370. doi: 10.1016/j.ygyno.2015.11.023. Epub 2016 Feb 22.

Kesic V, Carcopino X, Preti M, Vieira-Baptista P, 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 Apr 3;33(4):446-461. doi: 10.1136/ijgc-2022-004213. PMID: 36958755; PMCID: PMC10086489.

Initial approval March 2018. Revised November 2019. Minor revision July 2021; Revised May 2023. Revised March 2025.

 

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