Human papillomavirus and nonhuman papillomavirus pathways to vulvar squamous cell carcinoma: A review

Vulvar squamous cell carcinoma (VSCC) is a rare tumor of the female genital tract. While previously considered a disease of older women, the epidemiologic landscape is changing with more young women diagnosed with VSCC and its precursor lesions. This may be secondary to the global increase in human papillomavirus (HPV) infection of the lower genital tract. While VSCC precursor lesions have been described for many years, the terminology, and thus the understanding and reproducibility of these lesions have been debated. In the most recent publication from the International Society of the Study of Vulvovaginal Disease (ISSVD), there is a distinction between high-risk vulvar lesions associated with HPV infection (vulvar HSIL) and high-risk vulvar lesions that are not thought to be associated with HPV infection (differentiated VIN or dVIN). These precursors have different risk factors and thus affect different populations, leading to two separate pathways for developing VSCC. The HPV-related VSCC is likely to have a better prognosis than the non-HPV-related VSCC, as seen in other disease sites. Early-stage VSCC may be surgically treated with margin and node status affecting whether adjuvant radiation is recommended. Advanced stage VSCC may be unresectable, requiring neoadjuvant chemoradiation. Although VSCC is a rare disease, ongoing studies investigating the different pathways leading to carcinogenesis may increase the understanding of VSCC and improve therapeutic options for patients.