Papillomaviruses in head and neck disease: pathophysiology and possible regulation

Human papillomaviruses (HPVs) are etiologic agents of both benign and malignant epithelial tumors. More than 60 different types of viruses are known, each associated with tissue site and lesion type specificities and differing probabilities of malignant progression. HPVs type 6 and type 11 cause benign papillomas of mucosal squamous epithelium in the aerodigestive tract, with only rare conversion to malignancy. HPV 16 is the most frequently detected HPV in the genital tract, inducing flat lesions with a significant risk of malignant conversion. In the aerodigestive tract, HPV 16 is found only rarely in benign lesions but is detected in 5-20% of squamous carcinomas. In the aerodigestive tract, HPVs frequently cause latent infection, i.e., viral DNA present in tissue but no evidence of clinical or histologic disease. Approximately 10% of the general population may have latent infections. Regulation and activation of latent infections are not well understood, although it is clear that viral functions are tightly regulated by the state of differentiation of the squamous host cell. Control of viral transcription may be the key to prevention of viral activation, and thus control of disease. Among the possible agents under investigation are retinoids, growth factors, anti-sense RNA which interferes with viral expression, and estrogen metabolites. All of these agents modulate either viral expression or cell differentiation or both. It is hoped that in the near future one or more of these agents will be useful in preventing HPV-associated disease.