HSV-2-induced tumorigenicity in HPV16-immortalized human genital keratinocytes.

A subgenomic region of HSV-2, BglII N, is capable of converting immortal genital epithelial cells containing integrated HPV16 sequences into tumorigenic squamous cell carcinoma cells. Moreover, tumor-derived cultured cells and immortal cells that had been transfected with HSV-2/Bg/II N and kept in continuous culture subsequently lost the HSV-2 sequences. The HSV-2/Bg/II N sequence was ineffective on normal cells. Thus, HSV-2/Bg/II N may act as a cofactor in the genesis of a carcinoma but is not required to maintain the transformed phenotype. Although papillomaviruses (HPVs) are currently receiving much attention because of their association with cervical squamous carcinomas, ample reasons exist to suggest a multifactorial etiology in which additional factors are necessary to convert dysplastic lesions to carcinomas. The hypothesis that specific HPV types may be necessary but not sufficient to cause cancer is reinforced. Thus, HSV-2-transforming sequences have a potential role in the etiology of human cervical cancer.