Cervical cancer risk factors

Overview
Cervical cancer is associated with a range of risk factors including, genetic, environmental and infection-based exposures.

Risk Factors
The American Cancer Society provides the following list of risk factors for cervical cancer:
 * human papillomavirus (HPV) infection
 * smoking
 * HIV infection
 * chlamydia infection
 * dietary factors
 * hormonal contraception
 * multiple pregnancies
 * use of the hormonal drug diethylstilbestrol (DES)
 * a family history of cervical cancer

Human papillomavirus infection
The most important risk factor in the development of cervical cancer is infection with a high-risk strain of human papillomavirus. Even though HPV is an important risk factor for cervical cancer, most women with this infection do not get cervical cancer and doctors believe other risk factors must come into play for this cancer to develop. Having unprotected sex, especially at a young age, makes HPV infection more likely. Women who have many sexual partners (or who have sex with men who have had many partners) have a greater chance of getting HPV.

More than 60 types of HPV are acknowledged to exist (some sources indicate more than 200 subtypes). Of these, 15 are classified as high-risk types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82), 3 as probable high-risk (26, 53, and 66), and 12 as low-risk (6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, and CP6108), but even those may cause cancer. Types 16 and 18 are generally acknowledged to cause about 70% of the cancer cases. Although most HPV infections clear up on their own, the infections could increase to major abnormalities or cervical cancer.

The presence of strains 16, 18 and 31 is the prime risk factor for cervical cancer, and Walboomers et al. (1999) reported that the presence of HPV is a necessary condition for the development of cervical cancer. A virus cancer link with HPV has been found to trigger alterations in the cells of the cervix, leading to the development of cervical intraepithelial neoplasia and cancer.

HPV subtypes 16 and 18 introduce the genes E6 and E7 which code for proteins that inhibit p53 and Retinoblastoma protein (Rb), which are two important tumor suppressor genes in humans. The p53 gene product is involved in regulation of apoptosis (cell suicide), and Rb is responsible for halting the cell cycle at the G1-phase. When Rb function is impaired, the cell is allowed to progress to S-phase and complete mitosis, resulting in proliferation and hence neoplastic transformation.

Genital warts are caused by different HPV types, and are not related to cervical cancer.

The medically accepted paradigm, officially endorsed by the American Cancer Society and other organizations, is that a patient must have been infected with HPV to develop cervical cancer, and is hence viewed as a sexually transmitted disease, but not all women infected with HPV develop cervical cancer (Snijders et al, 2006). Use of condoms does not always prevent transmission. Likewise, HPV can be transmitted by skin-to-skin-contact with infected areas. In males, HPV is thought to grow preferentially in the epithelium of the glans penis, and cleaning of this area may be preventative.

Despite the development of an HPV vaccine, some researchers argue that routine neonatal male circumcision is an acceptable way to lower the risk of cervical cancer in their future female sexual partners. Others maintain that the benefits do not outweigh the risks and/or consider the removal of healthy genital tissue from infants to be unethical as it cannot be reasonably assumed that a male would choose to be circumcised. There has not been any definitive evidence to support the claim that male circumcision prevents cervical cancer, although some researchers say there is compelling epidemiological evidence that men who have been circumcised are less likely to be infected with HPV. However, in men with low-risk sexual behaviour and monogamous female partners, circumcision makes no difference to the risk of cervical cancer.

In the Canadian provinces of Ontario, Prince Edward Island, Newfoundland and Nova Scotia, free vaccinations to protect women against HPV are slated to begin in September 2007 and will be offered to girls 11-14 in age. Similar vaccination programs are also being planned in British Columbia and Quebec.

Australia has decided to fund the HPV vaccine under the National Immunisation Program commencing in the 2007 school year. In the U.K. a similar free vaccination program is being considered, while in the United States, many states are preparing bills to handle issuing the HPV vaccine.