The group of precursors that lead to HPV-independent, p53-wild-type squamous cell carcinoma is largely unexplored. Nonetheless, a subset of lesions with verruciform acanthosis and altered squamous maturation has been characterized using diverse nomenclature such as VAAD, vLSC, DEVIL, and VAM. These lesions are associated with invasive squamous cell carcinoma and verrucous carcinoma of the vulva, and they harbor recurrent alterations in oncogenes like PIK3CA, HRAS, and NOTCH1.

Dr. Carlos Parra-Herran from the department of Pathology at Brigham and Women's Hospital discusses the importance of reproducibly in distinguishing these lesions from other squamous vulvar precursors and non-neoplastic mimickers with acanthosis or verruciform growth. In order to align with the WHO classification, his group proposes the unifying term of HPVi (p53wt) vaVIN.