Lenora R Garrett, Nuria Perez-Reyes, Patricia P. Smith, James K. McDougall; Interaction of HPV-18 and nitrosomethylurea in the induction of squamous cell carcinoma. Carcinogenesis 1993; 14 (2): 329-333. doi: 10.1093/carcin/14.2.329
A strong correlation exists between the presence of specific types of human papillomavirus (HPV) and the development of anogenital cancer, as well as significant epidemiologic evidence suggesting smokers are at increased risk of developing cervical, vulvar and/or anal carcinomas. Primary and human papillomavirus type 18 (HPV-8)-immortalized human keratinocytes were used to address the co-carcinogenic potential of HPV and nitrosomethylurea (NMU) in tumorigenesis. Only cells containing HPV-18 and treated with NMU and the tumor-promoting phorbol ester, TPA, were transformed to a malignant phenotype. An in vitro system is described which initiates studies involving the mechanisms of HPV and chemical carcinogen co-operation in the etiology of squamous cell carcinomas.