HPV, Human Papillomavirus

What is the human papillomavirus?

HPV is a group of more than 200 related viruses, some of which are spread through vaginal, anal, or oral sex.

Sexually transmitted HPV types fall into two groups, low risk and high risk.

• Low-risk HPVs mostly cause no disease. However, a few low-risk HPV types can cause warts on or around the genitals, anus, mouth, or throat.
• High-risk HPVs can cause several types of cancer. There are about 14 high-risk HPV types. Two of these, HPV16 and HPV18, are responsible for most HPV-related cancers.

HPV infection is common: Nearly all sexually active people are infected with HPV almost immediately once they become sexually active. Around half of these infections are with a high-risk HPV type.

Most HPV infections don’t cause cancer: Your immune system usually controls HPV infections so they don’t cause cancer.

High-risk HPV infections that persist can cause cancer: Sometimes HPV infections are not successfully controlled by your immune system. When a high-risk HPV infection persists for many years, it can lead to cell changes that, if untreated, may get worse over time and become cancer.

HPV vaccination can prevent cancer: HPV vaccines can prevent infection with disease-causing HPV types, preventing many HPV-related cancers and cases of genital warts.

Cancers Caused by HPV Infection

Long-lasting infections with high-risk HPVs can cause cancer in parts of the body where HPV infects cells, such as in the cervix, oropharynx (the part of the throat at the back of the mouth, including the soft palate, the base of the tongue, and the tonsils), anus, rectum, penis, vagina, and vulva. 

HPV infects the squamous cells that line the inner surfaces of these organs. For this reason, most HPV-related cancers are a type of cancer called squamous cell carcinoma. Some cervical cancers come from HPV infection of gland cells in the cervix and are called adenocarcinomas.

HPV-related cancers include:

• Cervical cancer: Virtually all cervical cancers are caused by HPV. Routine screening can prevent most cervical cancers by allowing health care providers to find and remove precancerous cells before they develop into cancer. As a result, cervical cancer incidence rates in the United States are decreasing.
• Oropharyngeal cancers: Most oropharyngeal cancers (70%) in the United States are caused by HPV. The number of new cases is increasing each year, and oropharyngeal cancers are now the most common HPV-related cancer in the United States.
• Anal cancer: Over 90% of anal cancers are caused by HPV. The number of new cases and deaths from anal cancer are increasing each year.
• Penile cancer: Most penile cancers (over 60%) are caused by HPV.
• Vaginal cancer: Most vaginal cancers (75%) are caused by HPV.
• Vulvar cancer: Most vulvar cancers (70%) are caused by HPV.

In the United States, high-risk HPVs cause 3% of all cancers in women and 2% of all cancers in men. There are about 44,000 new cases of cancer in parts of the body where HPV is often found, and HPV is estimated to cause about 34,000 cancers each year, according to the latest statistics from the Centers for Disease Control.

Worldwide, the burden of HPV-related cancers is much greater. High-risk HPVs cause about 5% of all cancers worldwide, with an estimated 570,000 women and an estimated 60,000 men getting an HPV-related cancer each year. Cervical cancer is among the most common cancers and a leading cause of cancer-related deaths in low- and middle-income countries, where screening tests and treatment of early cervical cell changes are not readily available.

How is HPV Transmitted?

HPV is transmitted through vaginal intercourse, anal and oral sex, and other intimate, skin-to-skin contact. The infection passes easily between sexual partners. Condoms and dental dams can reduce the likelihood of HPV transmission but do not completely prevent it.

Does HPV Infection Cause Symptoms?

No, infection with high-risk HPV does not cause symptoms. The precancerous cell changes caused by a persistent HPV infection at the cervix also do not cause symptoms. However, precancerous lesions at other sites in the body may cause symptoms. And if an HPV infection develops into cancer, the cancer may cause symptoms.

HPV Vaccination: Preventing HPV Infection

The HPV vaccine Gardasil 9® protects against infection with nine HPV types: the two low-risk HPV types that cause most genital warts, plus the seven high-risk HPV types that cause most HPV-related cancers.

HPV vaccination is recommended by the Centers for Disease Control and Prevention (CDC)’s Advisory Committee on Immunizations Practices (ACIP) to prevent new HPV infections and HPV-associated diseases, including some cancers.

HPV vaccination provides strong protection against new HPV infections, but the vaccine does not cure, and is not used to treat, HPV infections or diseases caused by HPV. HPV vaccination offers the most protection when given before someone is exposed to the virus. 

Who should get the HPV vaccine?

The HPV vaccine series is recommended for girls and boys at the age of 11 or 12; the series can be started at age 9. Children who start the series before age 15 need two doses to be protected. For young people who didn’t get vaccinated on time, HPV vaccination is recommended up to age 45; those who receive their first dose at age 15 or older need three doses to be protected. A fair warning, many insurance companies only cover it up to age 26 reflecting the older guidelines.

Can the HPV vaccine be given at older ages?

Yes, the vaccine can be given to adults between the ages of 27 and 45 who didn’t receive all vaccine doses earlier. In fact, it is now recommended. Adults in this age group benefit less from the vaccine because they are more likely to have been exposed to HPV already. But if you are concerned that you are at risk for new HPV infections, you should talk with your health care provider about whether the vaccine may be right for you. 

Screening for HPV and Cell Changes Caused by HPV

Screening tests are tests used to check for disease when there are no symptoms. The goal of screening for cervical cancer is to find precancerous cell changes at an early stage, even before they become cancer and when treatment can work to prevent cancer from ever happening. Currently, cervical cancer is the only HPV-caused cancer for which FDA-approved screening tests are available.

Screening for Cervical Cancer

Cervical cancer screening tests:

• the HPV test checks cervical cells for high-risk HPV
• the Pap test checks for cervical cell changes that can be caused by high-risk HPV
• the HPV/Pap cotest checks for both high-risk HPV and cervical cell changes

These screening ages and intervals apply to most women:

• Age 21-29 years: Pap testing every 3 years.
• Age 30-65 years: Screening using one of these tests:
  • HPV testing every 5 years
  • HPV/Pap cotesting every 5 years
  • Pap testing every 3 years 
• Older than 65 years: If you have been screened at regular intervals and your test results for the last decade have been normal, you may be advised that you no longer need to be screened for cervical cancer. Screening should continue past age 65 for women with recent abnormal Pap or HPV tests.

Depending on the test results and her age, a woman may have another test after 12 months, or she may have an exam called a colposcopy to allow her provider to examine the cervix and, if needed, remove a sample of tissue for analysis (a procedure called a biopsy).

What Does It Mean If a Woman Has a Positive HPV Test after Many Years of Negative Tests?

Sometimes, after a several negative HPV tests, a woman may have a positive HPV test result. This is not necessarily a sign of a new HPV infection, and it doesn’t mean that she or her partner has a new sexual partner. Sometimes an HPV infection can become active again after many years. Other viruses behave this way as well, for example the chickenpox virus can reactivate later in life to cause shingles.

There is no way to tell whether a newly positive HPV test result is a sign of a new infection or a reactivation of an old infection. Researchers don’t know whether a reactivated HPV infection has the same risk of causing precancer or cancer as a new HPV infection.

Screening for Other HPV-Related Cancers

There are no FDA-approved tests to detect HPV infections or HPV-caused cell changes in anal, rectal, vulvar, vaginal, penile, or oropharyngeal tissues. However, there is some evidence that, among populations that are at higher risk for HPV infection, such as men who have sex with men or men who are HIV-positive, anal Pap tests may help to detect early cell changes or precancerous cells. In anal Pap tests, a sample of anal cells is checked for abnormal cells.

Treatment for Cell Changes Caused by HPV Infection

Although HPV infection itself cannot be treated, there are treatments for the precancerous cell changes caused by infection with high-risk HPV.

• Precancerous cervical cell changes: Most women who have precancerous cervical cell changes are treated with the loop electrosurgical excision procedure (LEEP), which is a method to remove the abnormal tissue.
• Precancerous vaginal, vulvar, penile, and anal lesions; genital warts; and benign respiratory tract tumors: Treatment methods include topical medicines, surgical excision, cryosurgery, and LEEP.
• HPV-related cancers: Individuals who develop an HPV-related cancer generally receive the same treatment as patients with tumors at the same site that are not related to HPV infection. However, patients with HPV-positive oropharyngeal cancer may receive different treatments than patients whose oropharyngeal cancers are not caused by HPV. 

How Does HPV Cause Cancer?

Once high-risk HPV infects cells, it interferes with the ways in which these cells communicate with one another, causing infected cells to multiply in an uncontrolled manner. These infected cells are usually recognized and controlled by the immune system. However, sometimes the infected cells remain and continue to grow, eventually forming an area of precancerous cells that, if not treated, can become cancer. Research has found that it can take 10 to 20 years, or even longer, for HPV-infected cervical cells to develop into a cancerous tumor.

Among women whose cervical cells are infected with high-risk HPV, several factors increase the chance that the infection will be long lasting and lead to precancerous cervical cells:

• giving birth to many children
• using oral contraceptives for a long time
• smoking cigarettes