Lara Bonner Millar, MD & Carolyn Vachani, RN, MSN, AOCN
The Abramson Cancer Center of the University of Pennsylvania
Human papilloma viruses (HPV) are common viruses named for their ability to cause warts, also known as papillomas. This is a little misleading, however, as not all types of HPV cause warts. There are more than 150 types of HPV, of which about 40 can be transmitted sexually. Genital HPV infection is very common. Sexually active individuals have an 80-85% chance of being infected with HPV at some time in their lives. At any given time, as many as 20 million people in the US are thought to have an active HPV infection. Most strains of HPV do not cause problems, but about 30 strains can lead to cancer. HPV infections affect the skin, genitals, and oropharynx (mouth / throat), and are spread through genital skin-to-skin contact, masturbation, oral, vaginal or anal sex with another person (of either sex) who has HPV. A person who has HPV very likely will not show any signs of the virus. Because of this, people are unaware that they are infected.
The different strains of HPV are classified as either low-risk or high-risk. Low-risk HPV (i.e. HPV-6 and HPV-11) can cause genital warts—or no symptoms at all. HPV types 16 and 18 are examples of high-risk strains and are the cause of about 70 percent of cervical cancers. However, most women with HPV do not develop cervical cancer. It is important to know that the great majority of infections with high-risk HPV go away on their own (they are cleared by the immune system, usually within 2 years), and therefore do not lead to cancer.
Infection with high-risk HPV may or may not cause symptoms. However, if the infection persists for years, it can lead to cervical dysplasia, cancers of the cervix, and rarer forms of cancer, including vulvar, vaginal, and anal cancer in women. In men, it can lead to cancers of the anus and penis. Vaginal intercourse and anal penetration appear to be the most efficient modes of transmission, but they are not necessary to transmit the virus. Genital skin-to-skin contact and oral sex can spread the virus as well. Masturbation with a partner may even be sufficient to transmit the virus as HPV can be detected on the fingertips of woman and men who have genital warts!
In both genders, HPV has been associated with squamous cell carcinoma of the head and neck, particularly within the oropharynx (areas in the back of the mouth, base of the tongue and tonsils). While the majority (75%) of head and neck cancers are HPV-negative and are seen in older people who have a history or alcohol and/or tobacco use, HPV-associated head and neck cancers tend to affect younger individuals who do not have a strong smoking or alcohol history. In fact, HPV associated head and neck cancers are on the rise, while rates of head and neck cancers related to smoking and alcohol are decreasing. HPV can be transmitted to the head and neck area during oral sex. Experts do not know all of the ways that HPV can be transmitted, and studies are investigating whether deep kissing can transmit the virus to the oropharynx.
Anal HPV infection is common among men who engage in receptive anal intercourse with other men (though the risk applies to anyone engaging in receptive anal intercourse). Because of this increased risk, some clinics perform anal Pap smear testing on high-risk individuals to assess for pre-cancerous changes.
Why do some people's immune systems clear the infection, while others cannot and thus put them at risk for cancer? The reality is we don't know for sure, but we do know that smoking is one variable that increases the chance that the immune system will not clear the virus. Smoke is actually excreted through the tissue of the cervix! Other factors in women (as this is the population in whom most of the research has been done) include multiple childbirths, long-term oral contraceptive use and possibly chronic inflammation, though we don't know exactly why these factors increase risk.
It appears that the immune system can clear the active infection, but that the virus goes dormant and can be reactivated in times of lowered immunity. The large majority (more than 90%) of infections will clear on their own, but people with active infections that persist after 2 years are at highest risk of progression to cancer. The key is that these women (as we do not currently test for HPV in men) need to be vigilant with follow up and annual Pap testing to enable any pre-cancerous changes to be detected early, when they are easiest to treat.
Risk factors for HPV infection include being sexually active, although this is not limited to intercourse. Persons at higher risk for HPV infection include those with a history of many sexual partners (or partners with many partners), early age of first intercourse, and a history of other sexually transmitted infections. HPV infection can occur in both male and female genital areas that are covered by a latex condom, as well as in areas that are not covered, such as the scrotum and vulva. The degree of protection provided by condoms in preventing HPV infection is unknown, but condom use and dental dam use (during oral sex) can lower the rate of HPV transmission. Interestingly, males who are circumcised have a lower rate of HPV infection (and lower rates of certain other sexually transmitted diseases), although circumcision is not specifically recommended for HPV prevention. HPV vaccination, however, is recommended as prevention (see below).
Because most people's immune systems are able to clear the virus, risk of transmission may be lower for couples who wait longer to have sexual relations or have longer periods of abstinence between relationships, thus giving their bodies time to clear any infection before entering a new sexual relationship. Risk is lower for long-term, monogamous couples as well. In general, HPV infection lasts about 1 year in women and may be as short as 6 months in men, but this may vary depending on the strain. Shorter gaps between relationships may allow the infection to hop between partnerships, whereas longer periods of abstinence allow the infection to clear between sexual encounters.
The HPV vaccine protects against infection by certain strains of HPV that can cause cervical cancer and genital warts.
Two vaccines, Gardasil and Cervarix, are currently available to prevent cervical cancer in girls and young women. These vaccines do not treat cervical cancer, and females who receive the vaccine should still undergo routine Pap tests. Both of the vaccines protect against HPV-16 and HPV-18, the two types of HPV that are responsible for most cases of cervical cancer. Besides HPV-16 and 18, Gardasil also protects against HPV-6 and HPV-11, which cause about 90% of genital warts. Neither vaccine protects against all types of HPV, which is why Pap testing is still necessary. Gardasil is approved for females ages 9-26 years to protect against cervical cancer and genital warts and males ages 9 -26 to prevent genital warts. Cervarix is approved for females ages 10 – 26 to help protect against cervical cancer, but because it does not protect against the strains which cause warts, it is not approved for use in males.
Routine HPV immunization is recommended for 11- and 12-year-old girls. The vaccine is given in 3 shots over a 6-month period. The most common side effects are fainting, dizziness, nausea, headache, and skin reactions at the site where the shot was given.
While the HPV vaccine is believed to prevent cervical cancer, because the strains that cause cervical cancer also cause other forms of cancer, it is estimated that 40% of vulvar cancer, 60% of vaginal cancer, and 80% of anal cancer may be prevented by vaccination against HPV-16 and 18. Results from studies of vaccination to prevent non-cervical HPV infection are not yet available.
It is important to remember that the HPV vaccine does not protect against all types of HPV or other sexually transmitted infections such as HIV.
Cervical cancer is the second most common cancer in women worldwide. Approximately 500,000 new cases are diagnosed annually worldwide, mostly in developing countries. In the USA, it is estimated that there are about 12,000 cases of cervical cancer diagnosed yearly. Screening with Pap testing has resulted in dramatically lower rates of cervical cancer in many developed nations, but countries with fewer resources lag far behind in lowering the incidence of this disease.
The HPV vaccine does not protect against all types of HPV that lead to cervical cancer, therefore women should still receive regular screening, even after receiving the vaccine. Screening should include regular Pap smears to look for abnormalities, which can include pre-cancerous and cancerous lesions, as well as a manual pelvic exam to examine the entire genital area.
In addition to Pap testing, HPV testing can be done on cervical cells to identify high-risk types of HPV that may be present. HPV DNA testing is approved for follow-up testing of women with uncertain Pap results and for general cervical cancer screening of women over the age of 30 when done together with a Pap test. There is no approved screening test to find early signs of penile, vulvar, head-and-neck, or anal cancer. However, as previously mentioned, men who engage in receptive anal intercourse may benefit from anal pap screening. Learn more about this screening on the UCSF anal neoplasia research & treatment group website.
There is no medical treatment for HPV infections, but the cervical lesions and warts that can result from HPV infections are treatable. Options for treating pre-cancerous cervical lesions include cryosurgery (freezing), loop electrosurgical excision procedure (LEEP), which involves using a special wire loop to remove the abnormal cells, and conization, the surgical removal of a cone shaped piece of cervix. Skin warts can be treated with prescription creams or freezing.
Treatment of cancers related to HPV depends on the body site affected and the stage at diagnosis. Generally speaking, very early lesions can be managed by surgery alone (or in some cases, radiation alone). More advanced cases may require multimodality treatment, meaning some combination of surgery, radiation, and/or chemotherapy. Interestingly, HPV-positive oropharyngeal cancers are believed to be biologically different from head and neck cancers that do not contain HPV. Several studies have found that people with HPV-positive tumors of the head and neck have significantly improved survival after undergoing treatment. However, it is not clear if this means these types of tumors should be treated any differently from HPV-negative tumors. This is a question of interest to many researchers.
HPV viruses are extremely common in the general population and can be spread by skin-to-skin contact, including all forms of sexual contact. Most HPV infections are readily cleared by the body's immune system, but some may persist, and it is these that can lead to cancer. We still do not fully understand why some people are not able to clear the virus or all of the ways the virus can be spread. When "high-risk" HPV infections persist, they have the potential to cause cancer of anal and genital region, as well as the head and neck. The goal of HPV vaccination is to prevent infection with the virus, which should, in turn, decrease the occurrence of cervical cancer, but vaccination is not a "cure all" as vaccines do not cover all strains of the virus. It also remains to be seen if HPV vaccination can prevent other forms of cancer as well.
CDC HPV Topic Site
McGill University HITCH Cohort Study.
HPV.com, a website run by Merck, Inc., maker of one of the HPV vaccines.
Burchell AN, Tellier PP, Hanley J, Coutlée F, Franco EL. Influence of partner's infection status on prevalent human papillomavirus among persons with a new sex partner. Sexually Transmitted Diseases 37: 34-40, 2010.
Burchell, AN. Transmission of HPV: A brief timeline. Cervical Cancer Prevention. Cervical Cancer Prevention: In Press
De Vuyst H, Clifford G, Nascimento MC, et al. Prevalence and type distribution of human papilomavirus in carcinoma and intraepithelial neoplasia of the vulva, vagina, and anus: A meta-analysis. Int J Cancer 124:1626-1636, 2009.
Ganguly, N; Parihar, SP. Human papillomavirus E6 and E7 oncoproteins as risk factors for tumorigenesis. J Biosci 34 (1): 113–23, 2009.
Gillison ML. Human papillomavirus and prognosis of oropharyngeal squamous cell carcinoma: implications for clinical research in head and neck cancers". J. Clin Oncol 24 (36): 5623–5, 2006.
Ringström E, Peters E, Hasegawa M, et al. Human papillomavirus type 16 and squamous cell carcinoma of the head and neck. Clin Cancer Res 8 (10): 3187-92, 2002.
Palefsky J and Rubin M. The Epidemiology of anal human papillomavirus and related neoplasia. Obstet Gynecol Clin N Am 36:187-200, 2009.
Plummer M, Schiffman M, Castle PE, et al. A two-year prospective study of human papillomavirus persistence among women with a cytological diagnosis of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion. JID. 2007;195:1582-1589.
Schwartz SR, Yueh B, McDougall JK, et al. Human papillomavirus infection and survival in oral squamous cell cancer: a population-based study. Otolaryngol Head Neck Surg 125 (1): 1-9, 2001.
Tobian AA, Serwadda D, Quinn TC, et al. Male circumcision for the prevention of HSV-2 and HPV infections and syphilis. N Engl J Med. 360(13):1298-309, 2009.