As noted in Chapter 4, papillomaviruses infect a variety of vertebrate species including the hu- man. More than 70 different strains of papillomavirus have been isolated from the human (IARC, 1995). Most of these viruses are associated with a number of human conditions, both benign and malignant. Table 12.8 lists some of the more common strains and their association with specific human diseases. As noted in the table, the most common strains causally associ- ated with human cancer are types 16, 18, 31, and 45, while a number of other strains are asso- ciated with the development of benign lesions. The worldwide burden of human papillomavirus (HPV) infections is not known, but zur Hausen (1996) has pointed out that cervical cancer repre- sents the second most frequent malignant neoplasm in women worldwide, corresponding to ap- proximately 450,000 new cases per year or 5.8% of the global cancer incidence. If one accepts that more than 50% of anogenital cancers and 20% of oral, laryngeal, and nasal cancers contain
Key: LSIL, low grade squamous intraepithelial lesions; HSIL, high grade squamous intraepithelial le- sions.
Boldface numbers indicate those types most commonly associated with the lesion. Adapted from Stoler, 1996.
the high-risk HPV types, papillomavirus infections may be the cause of almost 10% of the worldwide cancer burden. The IARC (1995) has argued that more than 90% of all cervical can- cers are caused by infection with various types of HPV. HPV infection is also quite common in immunocompromised patients such as those with AIDS or transplants. A high rate of association with HPV infections in the skin is seen in the rare, inherited disease known as epidermodyspla- sia verruciformis. Affected individuals are extremely sensitive to widespread HPV infection in the skin, leading initially to various types of skin warts and to the development of multiple cuta- neous malignancies in about half of these infected patients (cf. Majewski and Jablonska, 1992). The genetic defects in the disease may involve two different genes, one of which is X-linked. The development of skin lesions also depends on cocarcinogenic effects of ultraviolet radiation and presumably some defect in the major histocompatibility complex and tumor necrosis factor locus and antigen presentation (Chapter 18). In homosexual men with AIDS, the relative risk of developing anorectal cancer associated with HPV may range up to 80% (IARC, 1995). Simi- larly, more than half in a series of renal transplant patients exhibiting nonmelanoma carcinomas of the skin had evidence of HPV infection in the neoplasms (Shamanin et al., 1996). As might be expected, human papillomaviruses are commonly found in normal skin of immunocompetent hosts (Astori et al., 1998).
By far the most common human neoplasm associated with HPV infection is carcinoma of the uterine cervix. The presence of HPV has been noted both in cervical dysplasia as well as in cervical intraepithelial neoplasia (CIN). Although HPV-associated cervical dysplasia and low- grade CIN may spontaneously regress (Kataja et al., 1989), persistent HPV infection is associ- ated with persistent cervical dysplasia (Ho et al., 1995); in higher grades of CIN, the incidence of HPV infection increases (Bergeron et al., 1992). Other risk factors associated with cervical HPV infections include current smoking, warts in sexual partners, and increasing frequency of sexual intercourse per week, especially with different partners (Kataja et al., 1993; Tortolero- Luna, 1999).