HPV-Associated Cancers

Cancer is a disease in which cells in the body grow out of control. Cancer is always named for the part of the body where it starts, even if it spreads to other body parts later.

Genital human papillomavirus (HPV) is the most common sexually transmitted infection in the United States. More than 40 HPV types can infect the genital areas of men and women, including the skin of the penis, vulva (area outside the vagina), and anus, and the linings of the vagina, cervix, and rectum. These types can also infect the lining of the mouth and throat.

HPV types are often referred to as “low-risk” (wart-causing) or “high-risk” (cancer-causing), based on whether they put a person at risk for cancer. The International Agency for Research on Cancer* found that 13 HPV types can cause cancer of the cervix; one of these types can cause cancers of the vulva, vagina, penis, anus, and certain head and neck cancers. The types of HPV that can cause Genital Warts are not the same as the types that can cause cancer.

Most people who become infected with HPV do not know they have it. Usually, the body’s immune system gets rid of the HPV infection naturally within two years. This is true of both high-risk and low-risk types. By age 50, at least 4 out of every 5 women will have been infected with HPV at one point in their lives. HPV is also very common in men, and often has no symptoms.

When the body’s immune system can’t get rid of a high-risk HPV infection, it can linger over time and turn normal cells into abnormal cells and then cancer. About 10% of women with high-risk HPV on their cervix will develop long-lasting HPV infections that put them at risk for cervical cancer. Similarly, when high-risk HPV lingers and infects the cells of the vulva, vagina, penis, anus, or certain areas in the mouth and throat, it can cause cell changes called precancers. These may eventually develop into cancer if they’re not found and removed in time. These cancers are much less common than cervical cancer. Much less is known about how many people with HPV will develop cancer in these areas.

Cancers Associated with HPV

Cervical cancer is the most common HPV-associated cancer. Almost all cervical cancer is caused by HPV. Some cancers of the vulva, vagina, penis, anus, and some cancers in areas of the head and neck (oral cavity and oropharynx) are also HPV-associated. Research is still being done to understand how and to what extent HPV causes these cancers.

According to a comprehensive study—

• About 90% of anal cancers are caused by HPV.
• About 40% of vulvar, vaginal, and penile cancers are linked to HPV.

Cancers of the head and neck are mostly caused by tobacco and alcohol, but recent studies* show that about 25% of mouth and 35% of throat cancers may be linked to HPV.

Most of the time, HPV goes away by itself within two years and does not cause health problems. It is thought that the immune system fights off HPV naturally. It is only when HPV stays in the body for many years that it can cause these cancers. It is not known why HPV goes away in most, but not all cases

Lowering Your Risk for HPV-Associated Disease

A vaccine is now available that protects against the types of HPV that most often cause cervical, vaginal, and vulvar precancers and cancers, as well as the types of HPV that cause most Genital Warts. At this time, the HPV vaccine has not been shown to prevent precancers or cancers in other areas of the body such as the anus, penis, or head and neck. The vaccine is given in a series of three shots and is recommended routinely for 11- and 12-year-old girls. The vaccine can also be given to girls and women aged 13 through 26 years who did not get any or all of the shots yet. The vaccine can be given beginning at age 9. Read CDC’s recommendations on the use of the HPV vaccine among United States females aged 9 through 26 years old. More information about CDC’s recommendations on the use of the vaccine can be found in CDC’s Morbidity and Mortality Weekly Report.

Cervical cancer can also be prevented or found early through regular screening (with the Pap test) and follow-up treatment. The Pap test (or Pap smear) looks for precancers (cell changes on the cervix that might become cervical cancer if they are not treated appropriately). The HPV DNA test may also be used with the Pap test for women aged 30 years and older. It looks for the virus that can cause these cell changes.

Currently, screening tests for other types of HPV-associated cancers are not widely recommended.

*Links to non-Federal organizations found at this site are provided solely as a service to our users. These links do not constitute an endorsement of these organizations or their programs by CDC or the Federal Government, and none should be inferred. CDC is not responsible for the content of the individual organization Web pages found at these links.

HPV and Cancer

Human Papillomaviruses and Cancer: Questions and Answers

What are human papillomaviruses, and how are they transmitted?
Human papillomaviruses (HPVs) are a group of more than 100 related viruses. They are called papillomaviruses because certain types may cause warts, or papillomas, which are benign (noncancerous) tumors. The HPVs that cause the common warts which grow on hands and feet are different from those that cause growths in the throat or genital area. Some types of HPV are associated with certain types of cancer (1). These are called high-risk, oncogenic, or carcinogenic HPVs.

Genital HPV infections are very common and are sexually transmitted. Of the more than 100 types of HPV, more than 30 types can be passed from one person to another through sexual contact. Although HPVs are usually transmitted sexually, doctors cannot say for certain when infection occurred. Most HPV infections occur without any symptoms and go away without any treatment over the course of a few years. However, HPV infection sometimes persists for many years, with or without causing cell abnormalities. This can increase a woman’s risk of developing cervical cancer.

What are Genital Warts?
Some types of HPV may cause warts to appear on or around the genitals or anus. Genital Warts (technically known as condylomata acuminata) are most commonly associated with two HPV types, HPV–6 and HPV–11. Warts may appear within several weeks after sexual contact with a person who is infected with HPV, or they may take months or years to appear, or they may never appear. HPVs may also cause flat, abnormal growths in the genital area and on the cervix (the lower part of the uterus that extends into the vagina). However, HPV infections of the cervix usually do not cause any symptoms.

What is the association between HPV infection and cancer?
Persistent HPV infections are now recognized as the major cause of cervical cancer. In 2007, it was estimated that 11,000 women in the United States would be diagnosed with this type of cancer and nearly 4,000 would die from it. Cervical cancer strikes nearly half a million women each year worldwide, claiming a quarter of a million lives. Studies also suggest that HPVs may play a role in some cancers of the anus, vulva, vagina, and penile cancer (cancer of the penis) (2).

Studies have also found that oral HPV infection is a strong risk factor for oropharyngeal cancer (cancer that forms in tissues of the oropharynx, which is the middle part of the throat and includes the soft palate, the base of the tongue, and the tonsils) (2, 3). Researchers found that an oral HPV infection and past HPV exposure increase the risk of oropharyngeal squamous cell cancer, regardless of tobacco and alcohol use, two other important risk factors for this disease. However, combining HPV exposure and heavy tobacco and alcohol use did not have an additive effect (3).

Are there specific types of HPV that are associated with cancer?
Some types of HPV are referred to as “low-risk” viruses because they rarely cause lesions that develop into cancer. HPV types that are more likely to lead to the development of cancer are referred to as “high-risk.” Both high-risk and low-risk types of HPV can cause the growth of abnormal cells, but only the high-risk types of HPV lead to cancer. Sexually transmitted, high-risk HPVs include types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, and 73 (4). These high-risk types of HPV cause growths on the cervix that are usually flat and nearly invisible, as compared with the external warts caused by low-risk types HPV–6 and HPV–11. HPV types 16 and 18 together cause about 70 percent of cervical cancers (4, 5). It is important to note, however, that the great majority of high-risk HPV infections go away on their own and do not cause cancer (5).

What are the risk factors for HPV infection and cervical cancer?
Having many sexual partners is a risk factor for HPV infection. Although most HPV infections go away on their own without causing any type of abnormality, infection with high-risk HPV types increases the chance that mild abnormalities will develop and progress to more severe abnormalities or cervical cancer. However, even among the women who do develop abnormal cell changes with high-risk types of HPV, only a small percentage would develop cervical cancer if the abnormal cells were not removed. As a general rule, the more severe the abnormal cell change, the greater the risk of cancer. Studies suggest that whether a woman develops cervical cancer depends on a variety of factors acting together with high-risk HPVs. The factors that may increase the risk of cervical cancer in women with HPV infection include smoking and having many children (5).

Can HPV infection be prevented?
The surest way to eliminate risk for genital HPV infection is to refrain from any genital contact with another individual.

For those who choose to be sexually active, a long-term, mutually monogamous relationship with an uninfected partner is the strategy most likely to prevent genital HPV infection. However, it is difficult to determine whether a partner who has been sexually active in the past is currently infected.

HPV infection can occur in both male and female genital areas that are covered or protected by a latex condom, as well as in areas that are not covered. Although the degree of protection provided by condoms in preventing HPV infection is unknown, condom use has been associated with a lower rate of cervical cancer.

In 2006, the U.S. Food and Drug Administration (FDA) approved Gardasil®, a vaccine that is highly effective in preventing infection with types 16 and 18, two “high-risk” HPVs that cause most (70 percent) cervical cancers (4), and types 6 and 11, which cause most (90 percent) Genital Warts (5).

How are HPV infections detected?
Testing samples of cervical cells is an effective way to identify high-risk types of HPV that may be present. The FDA has approved an HPV test as a follow-up for women who have an ambiguous Pap test (a screening test to detect cervical cell changes) and, for women over the age of 30, for general cervical cancer screening. This HPV test can identify at least 13 of the high-risk types of HPV associated with the development of cervical cancer. This test, which looks for viral DNA, is performed by collecting cells from the cervix and then sending them to a laboratory for analysis. The test can detect high-risk types of HPV even before there are any conclusive visible changes to the cervical cells. There are currently no approved tests to detect HPV infection in men.

How are cervical cell abnormalities classified?
A Pap test is used to detect abnormal cells in the cervix. It involves the collection of cells from the cervix for examination under the microscope. Various terms have been used to describe the abnormal cells that may be seen in Pap tests.

The major system used to report the results of Pap tests in the United States is the Bethesda System. In this system, samples with cell abnormalities are divided into the following categories:

• ASC—Atypical Squamous Cells. Squamous cells are the thin, flat cells that form the
surface of the cervix. The Bethesda System divides this category into two groups:

1. ASC–US—Atypical Squamous Cells of Undetermined Significance. The squamous cells do not appear completely normal, but doctors are uncertain what the cell changes mean. Sometimes the changes are related to HPV infection. An HPV test may be done to clarify the findings.

2. ASC–H—Atypical Squamous Cells cannot exclude a High-grade squamous
intraepithelial abnormality. Intraepithelial refers to the layer of cells that forms the surface of the cervix. The cells do not appear normal, but doctors are uncertain what the cell changes mean. ASC–H may indicate a higher risk of being precancerous compared with ASC–US.

• AGC—Atypical Glandular Cells. Glandular cells are mucus-producing cells found in
the endocervical canal (opening in the center of the cervix) or in the lining of the uterus. The glandular cells do not appear normal, but doctors are uncertain what the cell changes mean.

• AIS—endocervical Adenocarcinoma In Situ. Precancerous cells are found in the
glandular tissue.

• LSIL—Low-grade Squamous Intraepithelial Lesion. Low-grade means there are early changes in the size and shape of the cells. The word lesion refers to an area of abnormal tissue. LSILs are considered mild abnormalities caused by HPV infection and are a common condition, especially among young women. The majority of LSILs return to normal over months to a few years.

• HSIL—High-grade Squamous Intraepithelial Lesion. High-grade means that the cells look very different in size and shape from normal cells. HSILs are more severe abnormalities and may eventually lead to cancer if left untreated.

Pap test results may also be described using an older set of categories called the “dysplasia scale.” Dysplasia is a term used to describe abnormal cells. Although dysplasia is not cancer, it may develop into very early cancer of the cervix. The cells look abnormal under the microscope, but they do not invade nearby healthy tissue.

There are four degrees of dysplasia: mild, moderate, severe, and carcinoma in situ. Carcinoma in situ is a precancerous condition that involves only the layer of cells on the surface of the cervix, and has not spread to nearby tissues. In the Bethesda System, mild dysplasia is classified as LSIL; moderate or severe dysplasia and carcinoma in situ are combined into HSIL.

Cervical intraepithelial neoplasia (CIN) is another term that is sometimes used to describe abnormal tissue findings. Neoplasia means an abnormal growth of cells. The term CIN along with a number (1, 2, or 3) describes how much of the thickness of the lining of the cervix contains abnormal cells. CIN–3 is considered to be a precancerous condition that includes carcinoma in situ.

What tests are used to screen for and diagnose precancerous cervical conditions?
A Pap test is the standard way to check for any cervical cell changes. A Pap test is usually done as part of a gynecologic exam. The U.S. Preventive Services Task Force guidelines recommend that women have a Pap test at least once every 3 years, beginning about 3 years after they begin to have sexual intercourse, but no later than age 21.

Because the HPV test can detect high-risk types of HPV in cervical cells, the FDA approved this test as a useful addition to the Pap test to help health care providers decide which women with ASC–US need further testing, such as colposcopy and biopsy of any abnormal areas. (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.) In addition, the HPV test can be a helpful addition to the Pap test for general screening of women age 30 and over.

What are the treatment options for HPV infection?
Although there is currently no medical cure for human papillomavirus infection, the lesions and warts these viruses cause can be treated. Methods commonly used to treat lesions include cryosurgery (freezing that destroys tissue), LEEP (loop electrosurgical excision procedure, the removal of tissue using a hot wire loop), and conventional surgery. Similar treatments may be used for external genital warts. In addition, some drugs may be used to treat external genital warts (6). More information about treatment for genital warts can be found on the Centers for Disease Control and Prevention’s (CDC) Sexually Transmitted Diseases Treatment Guidelines Web page at http://www.cdc.gov/STD/treatment/ on the Internet.

What research is being done on HPV-related cancers?
Researchers at the National Cancer Institute (NCI), a part of the National Institutes of Health (NIH), and elsewhere are studying how HPVs cause precancerous changes in normal cells and how these changes can be prevented (7). Scientists are also developing HPV vaccines that will be stable at room temperature and that protect against more HPV types.

The goal is to develop a vaccine that does not require refrigeration for storage and distribution, which could allow for its use in many climates and locations.

Laboratory research has indicated that HPVs produce proteins known as E5, E6, and E7. These proteins interfere with the cell functions that normally prevent excessive growth. For example, HPV E6 interferes with the human protein p53. This protein is present in all people and acts to keep tumors from growing (8). This research is being used to develop ways to interrupt the process by which HPV infection can lead to the growth of abnormal cells.

Researchers at the NCI and elsewhere are also studying what people know and understand about HPV infection and cervical cancer, the best way to communicate the latest research results to the public, and how doctors are talking with their patients about HPV infection. This research will help to ensure that the public receives accurate information about HPV that is easily understood and will facilitate access to appropriate tests for those who need them.

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