It the last two posts we reviewed a discussion I had with a young woman who had misconceptions about the significance of an “abnormal Pap test” result early in her pregnancy. The point that was emphasized to her was the she did have genital warts and she did not have cancer. When she left, I think she had a better understanding of her condition, although I am also not sure she was completely convinced by my reassurances. Both anogenital warts and the most common forms of cervical cancer are clearly associated with human papillomavirus (HPV) infections, but the viruses that generally cause warts and the viruses that may lead to cancer are fundamentally (and biologically) very different beasts. Today, let’s digress with a brief overview of the HPV epidemic and mention the basic differences between HPV types.
To describe infection with HPV as widespread is a gross understatement – a better term would be ubiquitous. HPV is readily spread by intimate contact and most efficiently by sexual intercourse, although nonsexual routes of transmission (e.g., between mothers and newborns) and, rarely, fomite transmission (e.g., shared underwear) have also been documented. Condom use may reduce the risk but it is clearly not reliably protective. Among sexually active men and women, more than 50% will acquire an infection with one or more HPV types during their lifetimes. Risk for acquisition is directly related to lifetime number of sexual partners and early age of first intercourse. The CDC (Centers for Disease Control and Prevention) estimates that 80% of sexually active women will have evidence of a genital HPV infection by the time they are 50 years old.
Annually, in the U.S., 6-7 million individuals will acquire a genital HPV infection and more than 20 million will be dealing with active infections or complications related to the viruses. Three-quarters of all new HPV infections occur in sexually active individuals between 15-24 years of age among which there are more than 9 million currently infected. At any one time, about 1% of the sexually active adult population will have genital warts. In various studies, prevalence rates in women less than 25 years of age range from 28-46%. Fortunately, HPV infection in this group of women tends to be transient and is correlated with the development of a specific cell-mediated immune response to the virus (Schiffman, et al., J Natl Cancer Inst Monogr 2003;31:14-19). In one study of newly acquired HPV infections in college women, 70% of new HPV infections cleared within a year and 91% within 2 years with a median duration of infection of 8 months (Ho, et al. NEJM 1998;338:423-28). Persistent HPV infections are more likely to occur with oncogenic HPV types (see below), smokers, and in individuals who are immunosuppressed, such as those with diabetes, autoimmune disorders, organ transplants, and HIV infections.
Of the more than 120 different types of HPV, 25-30% are implicated in anogenital infections. Individuals may be infected with more than one HPV type and, indeed, there seems to be very little ‘cross-reactive’ immunity between different types. These viruses are divided by their innate biological properties into nononcogenic (noncancer-causing) types, such as HPV 6 and 11, the types which commonly cause more than 90% of anogenital warts, and the oncogenic types, such as HPV 16, 18, 31, 33, 45, the types associated with cervical intraepithelial neoplasia (or dysplasia) and cancer. HPV DNA can be found in 99.7% of invasive cervical cancer and the five oncogenic types listed here are associated with 63-97% of these malignancies worldwide. Unlike the nononcogenic types, the oncogenic HPV types are more likely to establish persistent infections and have the ability to integrate their DNA into the host genome. The production of two (at least) oncogenic proteins (E6 and E7) by these HPV types results in the inactivation of host cell factors (p53 and pRb) that usually limit cell proliferation. Although the pathway to cancer involves multiple steps, it is thought that the uncontrolled cell proliferation increases the risk of accumulating DNA damage that eventually leads to cancer.
With this information as an introduction, we will in our next post continue our discussion of cervical dysplasia and cancer in pregnancy and some of the special considerations to care that arise under these circumstances