Human papillomavirus (HPV)

ALSO KNOWN AS: Papovaviruses

ANATOMY OR SYSTEM AFFECTED: Anus, genitals, reproductive system, skin

DEFINITION: A group of viruses, some of which are sexually transmitted and associated with genital warts and several kinds of cancer

CAUSES: Viral infection spread through skin (usually sexual) contact

SYMPTOMS: Warts in genital and anal areas

DURATION: Acute in initial infection, then chronic and often recurrent

TREATMENTS:For warts: topical ointments, creams, resins, or gels and electrocautery, cryosurgery, or laser surgery; for cancer: chemotherapy, radiation, surgery; prevention possible with vaccine

Causes and Symptoms

Papillomaviruses are deoxyribonucleic acid (DNA) viruses than infect the skin and mucous membranes. Human papillomaviruses (HPV) belong to a group of papillomaviruses that consists of nearly 120 strains. Most strains are virtually harmless, causing nothing more than benign skin warts (papillomas), while others cause genital warts (condyloma acuminate) and can cause cancers of the cervix, vulva, vagina, penis, anus, and oropharynx.

Sexual contact is the primary mechanism by which the virus is acquired. About thirty HPV strains are sexually transmitted and can infect the external genitalia, urethra, anus, rectum, and sometimes the mouth and throat. Some low-risk strains cause genital warts, while the ten more virulent, high-risk strains cause abnormal Papanicolaou (Pap) tests and can in some instances cause cancer of the cervix, vagina, vulva, penis, scrotum, anus, and/or the mouth and pharynx. Almost all cases of cervical cancer are the result of persistent HPV infection.

HPV is one of the most common sexually transmitted diseases. It has been estimated that more than 50 percent of sexually active people and up to 75 percent of sexually active women will develop an HPV infection during their lifetimes. Although the active viral infection is usually cleared by the immune system within a few months, it often remains dormant and can later cause a reinfection. Babies of infected women may contract potentially life-threatening HPV infections during delivery.

Women are more susceptible to developing genital warts. Many infected people, however, do not have genital warts. Infected women who are asymptomatic are often diagnosed by an abnormal Pap testing. In 2003, the Food and Drug Administration (FDA) approved the use of testing for high-risk HPV DNA as a routine screening procedure. DNA testing is also used as a confirmatory test for HPV after an abnormal Pap test.

Frequent Pap tests are the best way to diagnose HPV infections in asymptomatic women. About 10 percent of HPV-infected women will develop precancerous changes in their cervix, and about 8 percent of these women will develop the early stages of cervical cancer. Since persistent HPV infection is a hallmark of developing cervical cancer and since the cancer usually develops slowly over five to ten years, early diagnosis and treatment can be effective in preventing cervical cancer.

Genital warts are highly contagious and are transmitted through skin-to-skin contact from sexual activity. Risk reduction for HPV infection can be achieved by reducing the frequency of sexual contact. Condom use may partially reduce the risk of HPV infection in women. Since condoms do not cover all infected areas, however, their use does not eliminate the risk of infection. Research has suggested that microbicides may prevent infection if they are applied before sexual activity.

Treatment and Therapy

Since there is no cure for an HPV infection, the primary treatments are for warts. Some treatments involve the use of topical ointments, creams, resins, and gels such as imiquimod (Aldara), podophyllin and podofilox (Condylox), and 5-fluorouracil, as well as trichloroacetic acid. Alternatively, warts may be removed by electrocautery, cryosurgery, laser, or conventional surgery.

In 2006, the FDA approved Gardasil, developed by Merck, and in 2009 approved Cervarix, developed by GlaxoSmithKline, for use as preventive vaccines for the most prevalent HPV strains that cause cervical cancer and genital warts. Gardasil is active against two HPV strains (16 and 18) that are the leading cause of genital warts and, as is Cervarix, active against two high-risk strains that cause up to 70 percent of cervical cancers in the United States. In 2010, the FDA approved the use of Gardasil for the treatment of precancerous lesions in an effort to prevent anal cancer. In 2014, the FDA approved Gardasil 9, which protects against seven HPV strains (16, 18, 31, 33, 45, 52, and 58) that cause anal, cervical, vulvar, and vaginal cancer and two strains (6 and 11) that cause genital warts. The US Centers for Disease Control and Prevention (CDC) recommends that all eleven- and twelve-year-olds receive the HPV vaccine to prevent the spread of HPV. HPV vaccines are given in three shots over six months. According to a 2022 study in the journal Pediatrics, the percentage of girls between the ages of thirteen and seventeen who received at least one HPV vaccine rose from 56 percent to 75 percent from 2015 to 2020. Routine Pap testing is still recommended for all women between the ages of twenty-one and sixty-five, because the vaccines do not protect against all strains of HPV.

Perspective and Prospects

HPV was first described as a cause of skin warts in 1907. The relationship between sexual activity and cervical cancer was noted when it was discovered that women who have or who have had multiple sexual partners have a greater risk of developing cervical cancer than do women who have had few or no sexual partners. It was not until the 1980s that HPV was linked to cervical cancer.

The mechanism by which HPV causes cancer has recently been determined. Two proteins encoded by HPV DNA attach to and inactivate cellular proteins that control cell division. With these cellular proteins inactivated, the cell multiplies uncontrollably. Current research is directed toward the development of a vaccine that would inactivate the viral proteins that bind to and inhibit the proteins controlling cell division. Since sisters of women with cervical cancer have a higher risk of developing cervical cancer, it is thought that genetics may also be involved in the progression of the disease.

The HPV vaccine has had a significant impact on HPV infection rates. Since the vaccine was introduced in 2006, vaccine-type HPV prevalence dropped by 56 percent among girls aged fourteen to nineteen in the United States. According to CDC, about 19,000 cancers caused by HPV occur in American women each year, and cervical cancer is the most common. About 8,000 cancers caused by HPV occur each year in men in the United States, and oropharyngeal (throat) cancers are the most common. However, improving vaccination rates will likely cause a significant decline in HPV-related cancers. In 2024, Merck announced plans to develop a new HPV vaccine that provided broader protection against multiple types of HPV. The vaccine is designed to treat women ages nine through forty-five to prevent many types of cancer caused by HPV types including cervical and vaginal.

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