Human papilloma virus (HPV) is spread via sexual activity. Nearly 40 million people in the United States are infected with HPV.
HPV can cause three different types of diseases, mostly in or around the genital area:
Warts: HPV can cause warts—small, raised, hard lumps that grow in clumps—to form in or around the vagina, anus, or the tip of the penis. Genital warts are sometimes called condylomata acuminata, or condylomas. Warts do not usually progress to cancer, but they can mean that pre-cancerous dysplasia is also present and should be looked for.
Dysplasia: Abnormal patches of cells found inside the anus or within the cervix (located at the lower end of the uterus, or womb), vagina and vulva (the labia and outer portion of the vagina). Unlike warts, dysplasia can't be felt or easily seen. Dysplasia is often referred to as a "pre-cancer" form of disease. Not all men or women with dysplasia go on to develop cancer.
Cancer (carcinoma): Dysplasia can develop into cancer. The four most common types of cancer caused by HPV are cervical cancer, anal cancer, rectal cancer, and penile cancer. HPV can also cause head and neck cancers, such as those involving the mouth or throat. If not diagnosed and treated early, these forms of cancer can be life-threatening.
HIV-positive people are more likely to be infected with HPV than HIV-negative people. HIV+ people are also more likely to develop genital warts, as well as cervical or anal cancer, and head and neck cancer, as a result of HPV. Unlike some types of cancers, whose rates have gone down since the introduction of potent combination antiretroviral therapy, anal and head/neck cancer rates have gone up and cervical cancer rates have stayed essentially unchanged. Researchers have stated that this is due, in part, to the fact that people are living much longer, but with imperfectly preserved or restored immune systems. Research is underway, however, to better quantify a person's risk for developing HPV-related cancers.
What are the symptoms and how is it diagnosed?
While a blood test can check for HPV infection, a positive result doesn't really say much. Being infected with HPV does not mean that genital warts will develop, nor does it mean that dysplasia or cancer will occur. Also, the blood test may falsely diagnose a person as not being infected with HPV when they actually have it.
Genital warts should be reported to a health-care provider. The warts should be biopsied—a sample collected in a minor surgical procedure—to determine if they might go on to cause cancer.
Cervical Dysplasia and Cancer
To check for cervical dysplasia or cancer, a health-care provider can perform a Pap smear, in which cells are scraped from the cervix and examined under a microscope.
Women should have their first cervical Pap smear by age 18 or when they become sexually active, whichever comes first. It is recommended that HIV-positive women have a cervical Pap smear every six months. Men and women who practice anal sex should also have regular anal Pap smears.
An abnormal Pap-smear result calls for closer examination. At this point, colposcopy—a procedure that uses a microscope to visualize the vagina and cervix during a pelvic exam—is used to look for cancerous or pre-cancerous patches, or lesions, on or around the cervix. These lesions are often referred to as cervical intraepithelial neoplasia (CIN). If lesions are found, a biopsy can be performed to learn more about the abnormal cells.
Depending on the results of the biopsy, CIN is given a stage number, either I, II, or III. The stage of dysplasia depends on the thickness of abnormal cells within the cervical wall. CIN I is considered to be a mild or "low-grade" form of dysplasia and generally does not require therapy (but must be monitored closely), whereas CIN II or III are considered to be more advanced or "high grade" forms of dysplasia and are more likely to develop into cancer. Advanced forms of CIN often require therapy to prevent them from developing into cancer.
Anal Dysplasia and Cancer
The best method of detecting anal dysplasia or cancer has not been determined. Some health care providers recommend routine anal Pap smears—the collection of cells lining the anal wall for analysis by a laboratory—followed by direct visualization, or anoscopy, if the results are abnormal. Other health care providers have doubts about the effectiveness of anal Pap smears and prefer to refer patients for much more sensitive direct visualization testing performed by a specialist. Either way, HPV experts recommend routine anal dysplasia testing for all HIV-positive men who have sex with men and women with a history of cervical dysplasia. Studies are also underway or planned to clarify which methods are best for monitoring anal dysplasia and to confirm that treating it may reduce the risk of developing anal cancer.
The University of California in San Francisco maintains a list of providers trained to conduct anoscopy and can be found here.
The staging system for AIN is similar to the one used for CIN, discussed above.
How is HPV treated?
The only treatments available are those to remove or destroy irregular cells, such as those that make up genital warts or cervical/anal dysplasia or cancer. Treatments aimed at the underlying cause of these problems—HPV—are still being studied.
As discussed above, therapy for genital warts and low-grade dysplasia are not required, but are often recommended to prevent them from advancing. Intermediate and high-grade dysplasia, as well as cervical or anal cancer, almost always require therapy to prevent them from becoming life-threatening problems.
Treating warts, dysplasia, and cancers depends on the location and severity of disease. Here's an overview of the currently available treatments and when they're usually used:
Topical medications: Topical gels and creams—such as podofilox, podophyllum, trichloroacetic acid, and imiquimod—are used only for the treatment of genital warts. In general, they have shown to be 30% to 80% effective in reducing wart size, sometimes dramatically. All topical treatments, with the exception of imiquimod, can be used to treat warts inside the anus or vagina. They are not effective for the treatment of anal or cervical dysplasia or cancer.
Cryotherapy uses liquid nitrogen to freeze warts or other abnormal cell patches (lesions; dysplasia) inside or near the genitals. This is one of the easiest treatments and can often be performed in a doctor's office. It is commonly used to treat genital warts and low-grade dysplasia It is not usually recommended for patients with intermediate or high-grade dysplasia
Laser treatment is more aggressive than cryotherapy and uses a high-powered light beam to burn and remove abnormal anal or cervical tissue. This is usually done in a hospital. Laser treatment is effective for intermediate and high-grades of dysplasia, provided that the entire lesion can be seen using either a colposcope or anoscope.
LEEP (loop electrical excision procedure) is a type of surgery and is almost always performed in a hospital. Like laser treatment, LEEP should not be used lesions that are too deep to see with either a colposcope or anoscope.
Surgery/cold-knife cone biopsy are still widely used. Cutting away the abnormal cervical or anal tissue allows for both an accurate diagnosis and effective treatment of dysplasia.
Radical surgery/radiation/chemotherapy: Cervical and anal cancer (carcinoma) are treated like other forms of cancer. Radiation and/or surgery are often necessary to either destroy or remove the cancer and the surrounding tissue. If the cancer spreads, chemotherapy is often used to kill cancer cells in other parts of the body.
An immune-based therapy called HspE7 is being developed as a way to prevent anal dysplasia from recurring in HIV-positive people. See the next section of this lesson regarding vaccines active against HPV.
Because the aim of treating dysplasia is to guard against the development of cancer, people who have had been diagnosed with CIN or AIN stage II or III should continue to be monitored closely even after successful treatment of lesions. Monitoring should include colposcopy or anoscopy.
Can it be prevented?
In May 2006, an advisory committee to the U.S. Food and Drug Administration (FDA) voted unanimously to recommend approval of Gardasil, a preventive vaccine developed by Merck & Co. Clinical trials have demonstrated that Gardasil is safe and effective for the prevention of cervical cancer and dysplasia of the cervix, vulva, and vagina. A similar vaccine, Cervarix, by GlaxoSmithKline, has also been approved by the FDA for young women and girls.
Gardasil and Cervarix protect against four types of HPV: types 6, 11, 16 and 18. HPV types 16 and 18 account for an estimated 70% of cervical cancer cases and can lead to vulvar and vaginal cancers. These HPV types are also believed to be the most common causes of anal cancer. HPV types 6 and 11 account for most genital wart cases and low-grade cervical and anal abnormalities. The Food and Drug Administration approved Gardasil to prevent genital warts in boys and men in October 2009 and expanded the approval for the vaccine to prevent the development of precancerous anal lesions in both men and women in December 2010.
The safety and effectiveness of Gardasil in HIV-positive people have not been determined.
Gardasil and Cervarix are most likely to be effective in people who have not yet been exposed to HPV. Because HPV is so easily and frequently transmitted via sexual activity, this means that the vaccines will likely need to be given to people before they become sexually active (for example, school-aged children). In other words, it is not clear if these vaccines will be useful to sexually active adults, including those infected with HIV. Studies in older HIV-negative women with a history of sexual activity, but no history of HPV infection, are underway.
For people who have anal (and possibly cervical) dysplasia caused by HPV, therapeutic vaccines are being studied. These vaccines are being developed to boost the immune response to the virus. This may help reduce the need for invasive treatments (such as those reviewed in the last section of this lesson) and/or reduce the risk of dysplasia recurring after successful treatment. One recent study involving Nventa Biopharmaceuticals' therapeutic vaccine HspE7 concluded that it is safe and potentially effective in HIV-positive men and women with anal dysplasia.
As for preventing the sexual transmission of HPV, a study published in June 2006 in the New England Journal of Medicine concluded that condoms can help reduce the risk of HPV transmission. The study, conducted by researchers at the University of Washington in Seattle, refutes the results of earlier analyses concluding that condom use does not reduce the risk of HPV infection.
According to the study results, women whose partners used condoms for all instances of vaginal intercourse were 70% less likely to acquire HPV than were women whose partners used condoms less than 5% of the time. Even women whose partners used condoms more than half the time had a 50% risk reduction, as compared with those whose partners used condoms less than 5% of the time. What's more, none of the women who reported consistent condom use had evidence of precancerous or cancerous cervical lesions, compared to some reports of precancerous lesions found in women who never or inconsistently used condoms for vaginal intercourse.
While this study did not look at the effectiveness of condoms for the prevention of anal HPV infection, the reduced risk of HPV infection via vaginal intercourse when condoms are used correctly and consistently suggests a similar benefit for men and women who engage in anal intercourse.
Regular anal/vaginal exams and Pap smears are crucial. While they can't prevent warts or dysplasia from occurring, they can help catch them before they progress and cause greater problems.
Are there any experimental treatments?
Yes. If you would like to find out if you are eligible for any clinical trials that include new therapies for the treatment or prevention of these HPV-related problems, visit ClinicalTrials.gov, a site run by the U.S. National Institutes of Health. The site has information about all HIV-related clinical studies in the United States. For more info, you can call their toll-free number at 1-800-HIV-0440 (1-800-448-0440) or email firstname.lastname@example.org.
Last Revised: February 10, 2016