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A Primer on HPV

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Reported by Nicole Gottlieb
April 24, 2002

Human papillomavirus (HPV) is now recognized as the major cause of cervical cancer, a disease that kills more than 200,000 women around the world each year. HPV is very common, however, and of the more than 100 types of HPV, fewer than 20 are considered "high-risk" for the development of cancer. The following is a brief guide to HPV, including transmission, incidence, treatment, and its connection to genital warts and cancer.

The Signs of HPV

Certain types of HPV may cause warts, or papillomas, which are benign (noncancerous) tumors. All warts are caused by papillomaviruses, but each type of HPV grows only on specific areas of the body. The HPV types that cause the common warts that grow on hands and feet are not transmitted sexually and differ from those that cause growths in the mouth and genital area.

About 40 types of HPV can be sexually transmitted and infect the genital area, including the cervix, vagina, vulva, anus and penis. HPV is, in fact, one of the most common sexually transmitted diseases, with many millions of new genital HPV infections occurring each year in the United States. As HPV rarely causes symptoms and therefore the majority of infections are unnoticed, genital HPV infections are likely to be even more common than we think.

Most genital warts are caused by HPV types 6 and 11. Warts may appear within several weeks or months after sexual contact with a person who has HPV, or they may never appear. HPVs may also cause flat, abnormal growths in the genital area and on the cervix. Again, HPV infections often do not cause any symptoms.

HPV Types and Their Association with Cancer

Research has clearly shown that HPVs are the major cause of cervical cancer. Studies also suggest that HPVs may cause a fraction of the cancers of the anus, vulva, vagina, and penis, and some cancers of the oropharynx (the middle part of the throat that includes the soft palate, the base of the tongue, and the tonsils).

Some types of HPVs are referred to as "low-risk" viruses because they rarely develop into cancer; these include HPV-6 and HPV-11, although the most common low-risk types cause neither warts nor cancer. HPVs that can lead to the development of cancer are referred to as "high-risk." Both high-risk and low-risk types of HPVs can cause the growth of abnormal cells, but usually only the high-risk types may lead to cancer. Sexually transmitted, high-risk HPVs have been linked with anogenital cancer in both men and women, and include HPV types 16, 18, 31, 33, 39, 45, 51, 52, 56, 58, 59, 68 and 69. These high-risk types of HPVs cause growths that are usually flat, as compared with the warts caused by HPV-6 and HPV-11.

Risk Factors for HPV and Cervical Cancer

Women who have many sexual partners have a higher chance of developing an HPV infection in the cervix. Infection with high-risk HPV types, specifically, increases the odds that a woman will develop cervical cancer. However, while HPV infections are very common, cervical cancer is not. The vast majority of HPV infections go away without treatment and do not cause cervical cancer. Studies suggest that development of cervical cancer depends on a variety of factors acting on women with high-risk HPVs. These cofactors include: smoking, having many children, long-term oral contraceptive use, and HIV infection. Effective screening and treatment of precancerous cervical conditions is highly effective in the prevention of cervical cancer in HPV-infected women.

Precancerous Cervical Conditions

Abnormal cervical cells can be detected when a Pap test is done during a gynecologic exam. Various terms have been used to describe the abnormal cells that may be seen in Pap tests. The Bethesda System (the major system used to report the results of Pap tests) divides the most common clearly abnormal Pap test results into low-grade squamous intraepithelial lesions (LSILs), high-grade squamous intraepithelial lesions (HSILs), and cancer. Squamous cells are thin, flat cells that cover internal (e.g. cervix) and external (e.g. skin) surfaces of the body. LSILs are mild cell changes due to HPV infections, which are common, especially in young women. The majority of LSILs return to normal over months to a few years but, if HPV persists, HSIL can develop. HSILs are not cancer, but they may eventually lead to cancer and should be treated by a doctor.

Screening and Follow-up for Cervical Conditions

Screening for cervical cancer consists of regular Pap tests for women who have been sexually active for approximately three years or who have reached 21 years of age. Women 65 to 70 years of age who have had at least three normal Pap tests and no abnormal Pap tests in the last 10 years may decide, upon consultation with their healthcare provider, to stop cervical cancer screening. Women who have had a total hysterectomy (removal of the uterus and cervix) do not need to undergo cervical cancer screening, unless the surgery was done as a treatment for cervical precancer or cancer.

According to the new 2001 Consensus Guidelines for Managing Women with Cytological Abnormalities, if either HSIL or LSIL is found on a Pap test, colposcopy and biopsy of any abnormal areas are recommended. Colposcopy is a procedure in which a lighted magnifying instrument called a colposcope is used to examine the vagina and cervix. Biopsy is the removal of a small piece of tissue for diagnosis.

Testing for HPV

There currently is only one FDA-approved, commercially available test for HPV, the Hybrid Capture, produced by Digene Corporation. Like the Pap test, the HPV test examines cells taken from the cervix (or anus). There is now an increasing number of laboratories around the country to which doctors can send specimens for HPV analysis. The HPV test checks directly for genetic material (DNA) of HPV, and may be used to determine which women with an ambiguous Pap test result known as ASC-US (atypical squamous cells of undetermined significance) are most likely to have underlying precancerous or cancerous changes on their cervix. For women diagnosed with LSIL or HSIL, the test will almost always be positive, so HPV testing does not generally provide additional helpful information for women with those results.

The HPV test looks specifically for certain high-risk HPV types that are known to be associated with cervical cancer. A positive test means that one of the types of HPV being tested is present, and the amount is enough to cause an infection.

It is not known how often women should get an HPV DNA test. Use of HPV DNA testing to extend Pap test screening intervals is under active consideration.

Transmission of HPV

It is very easy to spread the virus to a sexual partner. Although using a condom is a good idea to prevent transmission of other infections or diseases, condoms may not protect sexual partners from genital HPV infections. HPV infections usually are not limited to the penis or the vagina. The infection can occur on the skin in the genital area, such as the scrotum, vulva, anus, or the skin between the anus and the genitalia - areas that are not protected with normal condom use. It is not known if transmission can occur when the virus levels are very low or undetectable.

Treatment of HPV Infection

Although there is currently no medical cure to eliminate HPV, the high-grade cell changes (HSILs) and warts caused by HPV can be treated. Methods used to treat HSILs include cryosurgery (freezing that destroys tissue), LEEP (loop electrosurgical excision procedure, the removal of tissue using a hot wire loop), as well as conventional surgery. Similar treatments may be used for external genital warts. In addition, topical treatments such as Podofilox and Imiquimod may be applied to destroy genital warts. LSILs often are not treated, as most of these cell changes will go away on their own.

Current Research on HPV and Cervical Cancer

The ASCUS/LSIL Triage Study (ALTS), a major study organized and funded by the National Cancer Institute (NCI), has evaluated different management approaches for women with mildly abnormal Pap test results. Findings from ALTS demonstrate that testing cervical samples for HPV is an excellent option to help direct follow-up for women with an ASC-US Pap test result.

Researchers at NCI and other sites are studying how HPVs cause precancerous changes in normal cells and how these changes can be prevented. They are using non-infectious HPV-like particles created in the laboratory as preventive vaccines against the viruses. Investigators are conducting clinical trials to test vaccines for certain papillomaviruses, such as HPV-16 and HPV-18, which are known to be particularly high-risk for the development of cervical cancer. It is hoped that a vaccine will be available within 10 years to prevent the most common HPV infections.


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