A Systematic Review of Risk Factors for Development, Recurrence, and Progression of Vulvar Intraepithelial Neoplasia

Abstract

Objective: Vulvar intraepithelial neoplasia (VIN) is a premalignant condition with high recurrence rates despite treatment. Vulvar intraepithelial neoplasia develops through separate etiologic pathways relative to the presence or absence of human papillomavirus (HPV) and TP53 mutations. This systematic review was conducted (1) to identify historical risk factors for the development, recurrence, and progression of VIN and (2) to critique these risk factors in the context of advances made in the stratification of VIN based on HPV or TP53 status. Materials and Methods:A systematic search was performed on MEDLINE, Embase, Cochrane Database, PsychInfo, and CINAHL from inception to July 5, 2021. Three gynecologic oncologists independently evaluated the eligibility of studies based on predetermined inclusion and exclusion criteria, abstracted data, and then analyzed the relevant data.Results: A total of 1,969 studies (involving 6,983 patients) were identified.Twenty-nine studies met inclusion criteria. The quality of evidence was low; primarily level 2b (Oxford Centre for Evidence-Based Medicine). Risk factors associated with the development of VIN include: smoking and coexisting vulvar dermatoses. Risk factors associated with recurrence include: smoking, multifocal disease, and positive surgical margins. Recent studies identified the presence of differentiated VIN/TP53 mutation as the most significant risk factor for both VIN recurrence and malignant progression. Conclusions:The current body of evidence consists primarily of small retrospective observational studies. Well-designed retrospective case-control series and/or prospective observational studies are urgently needed. Ideally, future studies will collect standardized data regarding associated risk factors and stratify women with VIN based on HPV and TP53 status.

Exploring the potential prompting role of cervical human papilloma virus detection in vulvar lesions: a cross-sectional study in China

“…The average age of our patients with VIN2/3 was 51.5 years and 59.9 for those with VSCC. This is consistent with previous research showing that the risk for VIN2/3 and VSCC increases with age (>50 years) ( 16 ). Among our patients with NNEDV, 25.6% were older than 65 years.…”

“…HPV detection and genotyping were tested using HybriMax HPV Geno-Array kit (Hybribio Biotechnology Limited Corp., Chaozhou, China) with flow-through hybridization and gene-chip methods, according to the manufacturer's instructions. The HPV Geno-Array can determine 21 HPV types, including 15 high-risk HPV (hrHPV) types (16,18,31,33,35,39,45,51,52,53,56,58,59, 66, and 68) and 6 low-risk HPV types (6,11,41,42,44, and CP8304) (8, 9).…”

A Scoping Review of Treatment Outcome Measures for Vulvar Intraepithelial Neoplasia

“…Considering the natural history of VIN, and the differing clinical trajectories between HSIL and differentiated VIN, it may be helpful to develop standards regarding when posttreatment vulvar biopsies and/or HPV tests are done in research studies. Our recently published systematic review of risk factors for the development, recurrence, and progression of VIN reported that the mode of treatment did not seem to influence risk of progression to cancer 41 . Rather, the absence of HPV and presence of TP53 mutations were major risk factors for VIN recurrence and malignant progression.…”

“…Our recently published systematic review of risk factors for the development, recurrence, and progression of VIN reported that the mode of treatment did not seem to influence risk of progression to cancer. 41 Rather, the absence of HPV and presence of TP53 mutations were major risk factors for VIN recurrence and malignant progression. In this review, only 5 of 29 studies stratified treatment outcomes based on HPV or TP53 status.…”

Multicentricity and the Risk of Recurrence/Persistence After Laser Vaporization for High-Grade Vulvar and Vaginal Intraepithelial Neoplasia

“…Several prognostic factors have been shown to affect recurrence after treatment of VIN/VAIN, such as age, immunosuppression, human papillomavirus (HPV) persistence, smoking, method of treatment, large lesion size, multifocal lesions, and multicentric lesions [3,4,[6][7][8][10][11][12][13][14][15]. The concept of multicentric lower genital tract disease, defined as intraepithelial lesions or cancer at two or three sites (cervix, vagina, and vulva), is well recognized [1,7,13,[16][17][18].…”