Human Papillomavirus: Natural History of a Viral Infection in the Genesis of a Cancer

Abstract

Human Papillomaviruses (HPV) are small deoxy-ribonucleic acid (DNA) tumor viruses with an icosahedral virion structure associated with a wide spectrum of epithelial lesions, ranging from benign warts to invasive carcinomas. They have been difficult to study, in part because they have not yet been propagated in tissue culture. Fortunately, advances in molecular biology have allowed characterization of HPV genomes and identification of some HPV gene functions. In addition to their clinical importance, HPV represent an important tool for exploring virus-cell interactions, gene expression, cellular differentiation, and cancer. HPV infections are not only common, but also difficult to treat and prevent. Depending on the HPV type and location, the modes of HPV transmission may involve casual physical contact, sexual contact, and perinatal vertical transmission. HPV DNA genomes replicate at a low copy number in basal cells and, as most clinicians know, are difficult to eradicate. There is often a long latent period and subclinical infections, plus HPV DNA can be found in normal tissue adjacent to lesions. HPV can cause widely disseminated lesions, especially in the immuno-compromised host and in epidermodysplasia verruciformis (EV). In malignant lesions, HPV DNA is also found as fragments incorporated into the cellular genome. Unlike retroviruses such as Human Immunodeficiency Virus (HIV) that integrate into the cellular genome as part of their life cycle, HPV integration is a terminal event for viral replication. Such integration is critical, however, for viral-induced abnormal cell growth. Perhaps the most important implication of some ano-genital cancers is that they may be preventable. The data overwhelmingly suggests that avoidance of exposure to HPV, via abstinence or monogamy in both partners markedly reduces the risk of cervical cancer. A more realistic goal, however, is prevention of HPV transmission by the use of barrier method contraceptives, which may be protective against development of cervical carcinoma as reported byCripe (Pediatr Infect Dis J 9:836–844, 1990). Infection with HPV is the most common STD, afflicting approximately 80% of the population. HPV infection is an essential factor in cervical carcinogenesis and cervical carcinoma the second most common cause of cancer among women worldwide. In addition to cervical cancer, other malignancies in both men and women such as esophageal, oropharyngeal, and anal cancer have been causally associated with this virus. Other gender-specific HPV-related cancers include penile, vulvar, and vaginal cancer. Recent evidence also points to a possible role of other HPV infections in squamous cell carcinomas (SCC) of the skin. During the past 20 years, several types of HPV have been identified that cause specific types of cancers. The etiology of cancer of the cervix has been linked to several types of HPV, with a high preponderance of HPV-16. HPV-16 is the most common HPV type associated with a malignant phenotype regardless of organ of origin. HPV-16, together with HPV-18, accounts for approximately 70% of cervical cancers. Other non-oncogenic HPV types, including HPV types 6 and 11, are associated with over 90% of benign HPV-related lesions such as genital warts and juvenile respiratory papillomatosis as reported by Monk and Tewari (Gynecol Oncol 107:S6–S13, 2007).