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Human Papilloma Virus (HPV) Infection and Non-Cervical Oncogenic Disease States

Cristina Merkhofer and Joel Maslow

Human papillomavirus (HPV) infection is causative for cervical cancer and has been implicated in cancers at other sites. We review the English language literature in regard to the epidemiology of HPV infection as a risk for non-cervical cancer with a focus on the molecular evidence to support HPV having an etiologic role at each anatomic site. HPV DNA is detected in and/or serology provides evidence that HPV is associated with 35-50% of penile cancers, 80-95% of anal cancers, and ~35% of oropharyngeal cancers. HPV has also been implicated for cancer of the larynx, esophagus, lung, and urinary bladder with varying levels of linkage. Molecular studies at the respective anatomic sites provide evidence of HPV integration, E6 and E7 oncogene expression coupled with tumor suppressor down-regulation consistent with a role in the pathogenesis of tumor formation. HPV-associated cancer may represent a distinct disease entity relative to non HPV-associated cancers based upon natural history and outcome studies. Thus, the disease burden of HPV associated non-cervical cancers may be significant and justifies a comprehensive investigation of the utility of global prophylactic vaccination strategies.