Understanding The Cause of Cervical Cancer
What Is Cervical Cancer?
The cervix forms the opening to the uterus from the vagina. It is covered with two main types of cells: squamous cells, which cover the part of the cervix that extends into the vagina, and columnar cells, which line the cervical opening. Most cervical cancers develop close to where these two cell types come together, in an area called the transformation zone. Once cervical cancer develops, it can spread throughout the cervix to neighboring organs or to distant sites in the body.
Cancerous and precancerous changes in cervical cells are often first detected by a Pap test, wherein a sample of cells is removed from the cervix using a small wooden or plastic spatula and a brush. The cells are then examined under a microscope in a laboratory. If Pap test results are abnormal, a physician may perform a colposcopy, using a microscope called a colposcope to better see the cervix. The physician applies a mild vinegar solution to the cervix, which makes abnormal cells appear more white than pink. If abnormal areas are identified, the physician may remove samples of tissue so that the cells can be further evaluated—a procedure called a biopsy.
The results of the biopsy allow the physician to diagnose cancer or precancerous conditions. Precancerous changes to the cervix are called cervical intraepithelial neoplasia (CIN). The severity of CIN is graded on a scale of 1 to 3, with 3 being the most severe. CIN2 and CIN3 are considered “high-grade” CIN and may progress to cancer if not treated.
What Is HPV?
There are more than 100 different types of human papillomavirus (HPV), and different types of HPV cause different conditions. Some types of HPV are linked with common skin warts, others cause genital warts, and still others are linked with cancers of the cervix, vulva, vagina, penis, and anus as well as some cases of head and neck cancer. HPV types 6 and 11 account for a majority of cases of genital warts, and HPV types 16 and 18 cause roughly 70 percent of all cases of cervical cancer. The remaining cases of cervical cancer are linked with other high-risk types of HPV.
The types of HPV that cause genital warts or cervical cancer are transmitted sexually. Sexual transmission of HPV is extremely common and generally occurs soon after an individual becomes sexually active. Most infections resolve on their own, but others persist. Persistent infection with a high-risk type of HPV can lead to precancerous changes to the cervix and, if these changes are not treated, to cervical cancer.
How is HPV linked to Cervical Cancer?
The sexually transmitted types of HPV most commonly linked with cervical cancer are HPV 16 and HPV 18 (transmitted sexually), but several other high-risk types contribute to cancer as well.
Though a link between cervical cancer and a sexually transmitted infection was long suspected, studying HPV was historically a challenge because it could not be grown in cell or tissue cultures like some other organisms. It would take the molecular techniques that were introduced in the 1970s to adequately study and understand the virus. Once these techniques were applied, it became apparent that most cervical cancers contained evidence of HPV.
Infection with a high-risk type of HPV does not necessarily lead to cancer. Many infections disappear on their own, and others may persist without causing cancer. Infection does, however, increase the risk of cancer, and virtually all cases of cervical cancer can be linked to infection with a high-risk type of HPV.
Is There a Test for HPV?
The recognition that specific types of HPV are the cause of cervical cancer led to the development of tests to identify women infected with high-risk types of HPV. Information about HPV status may guide decisions about follow-up care.
HPV testing may also have a role in initial cervical cancer screening, but conclusive evidence about this is still lacking. In the meantime some organizations have supported the combination of HPV testing and Pap testing for screening women over the age of 30. Women who test negative for both tests may need not be rescreened for up to three years. The combination of HPV testing and Pap testing is not recommended for screening younger women because most will have HPV infections that will clear without causing precancerous cervical lesions.
What are HPV Vaccines and How Might They Prevent Cervical Cancer?
HPV vaccines fall into two broad categories: preventive and therapeutic. Preventive vaccines are designed to prevent infection with the virus, whereas therapeutic vaccines would treat the infection, precancerous lesion, or cancer in individuals who are already infected. Although prevention of infection is the ultimate goal, treatment of existing infections and cervical changes would benefit the many women who are currently infected.
The two vaccines that are farthest along in development are preventive vaccines. Gardasil™, developed by Merck, targets HPV types 6 and 11 (which are linked with genital warts) as well as the cancer-associated types 16 and 18. Cervarix™, developed by GlaxoSmithKline, targets HPV types 16 and 18 only. Clinical trials of these vaccines suggest that they are likely safe and highly effective. The duration of effectiveness is still uncertain, but it appears to be at least four to five years. Because HPV types 16 and 18 are thought to account for roughly 70 percent of all cases of cervical cancer, widespread use of these vaccines would have the potential to eliminate most (but not all) cases of cervical cancer and precancerous changes to the cervix.
Because infection with HPV is extremely common and generally occurs soon after an individual becomes sexually active, the vaccines are likely to have the greatest effect when administered before the teen years. In addition to being less likely than older children to be sexually active, younger children versus older adolescent and young adult women appear to develop a stronger immune response after HPV vaccination. This may increase vaccine effectiveness.
It is thought that for these vaccines to have the greatest impact it will ultimately be important to vaccinate both girls and boys. Vaccinating a larger number of individuals will reduce transmission of these viruses in the community and will make it less likely that an unvaccinated individual will become infected. Furthermore, in addition to reducing the risk of cervical cancer, the vaccines are likely to reduce the risk of other HPV-related cancers, such as cancer of the penis, anus, and oropharynx (part of the throat). Protection against genital warts would also benefit both boys and girls.
Gardasil and Ceravix are both approved by the U.S. Food and Drug Administration (FDA) for use in girls and women between the ages of nine and 26 years.
- Jastreboff AM, Cymet T. Role of the human papilloma virus in the development of cervical intraepithelial neoplasia and malignancy. Postgraduate Medical Journal. 2002;78:225-228.