All About HPV
What is HPV?
Human papilloma viruses (HPV) are common viruses named for their ability to cause warts, also known as papillomas. Actually, not all types of HPV causes warts. There are more than 200 types (or strains) of HPV, of which about 40 can be transmitted sexually. Most strains of HPV do not cause problems, but several can cause genital warts and 12 types are known to cause cancer. Genital HPV infection is very common, affecting about 80 million Americans in their lifetime. Sexually active individuals have an 80-85% chance of being infected with HPV at some point in their lives.
HPV can infect the skin, genitals, and oropharynx (mouth/throat), and are spread through genital skin-to-skin contact, masturbation, and oral, vaginal, or anal sex with another person (of either sex) who has HPV. A person who has HPV will usually not have any symptoms from the virus. Because of this, people do not know that they are infected.
High-Risk Versus Low-Risk
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 easiest ways to spread the infection, 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 women 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, the base of the tongue, and tonsils). Historically, the majority of head and neck cancers were seen in older people who have a history or alcohol and/or tobacco use. In recent years there has been a dramatic shift, with a rise in HPV-associated head and neck cancers, which tend to affect younger people 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 or other behaviors 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.
Clearing the Infection
Why do some people's immune systems clear the infection, while others cannot and thus puts them at risk for cancer? 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 a woman's 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 the 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.
HPV Infection Prevention
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, as well 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, the 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, vaginal, vulvar, and anal cancer and genital warts. There are 3 HPV vaccines produced, though, in the United States, only Gardasil 9 is available.
- Ceravix protects against HPV 16 & 18.
- Gardasil protects against HPV strains 16, 18, 6 & 11.
- Gardasil 9 protects against HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58.
This vaccine does not treat cancer. Females who receive the vaccine should still undergo Pap testing as recommended by their provider because it does not protect against all types of HPV. HPV-16 and HPV-18, are responsible for most cases of cervical cancer. HPV-6 and HPV-11, cause about 90% of genital warts.
HPV vaccines are recommended for all individuals (female and male) ages 12-26. It is given in 2 or 3 doses, depending on the age you are when it is started. The US Food & Drug Administration has approved the vaccine for use in individuals up to age 45, though most insurance companies will not cover beyond age 26 and it is not recommended for routine use after age 26 by any professional organizations. The most common side effects after the injection 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 49% of vulvar cancers, 55% of vaginal cancers, and 79% of anal cancers may be prevented by vaccination against HPV-16 and 18.
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, with about 500,000 new cases per year, most in developing countries. In 2016, approximately 12,820 cases will be newly diagnosed in the US. 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.
The American Cancer Society recommends the following guidelines for cervical cancer screening:
- All women should begin cervical cancer screening at age 25.
- Women between the ages of 25 and 65 should have:
- Primary HPV testing every 5 years. This test is not yet available at many centers/practices.
- If this test is not available, you should be screened with co-testing, which is a combination of an HPV and Pap test. This should be done every 5 years.
- If HPV testing is not available, then a Pap test alone should be performed every three years.
- Women over age 65 who have had regular cervical screenings that were normal should not be screened for cervical cancer.
- Women who have been diagnosed with cervical pre-cancer should continue to be screened until they meet one of the following criteria over the previous 10 years:
- Two negative, consecutive HPV tests.
- Or 2 negative, consecutive co-tests.
- Or 3 negative, consecutive pap tests in the last 3-5 years.
- Women who have had their uterus and cervix removed in a hysterectomy and have no history of cervical cancer or pre-cancer should not be screened.
- Women who have had the HPV vaccine should still follow the screening recommendations for their age group.
- While the ACS does not recommend cervical cancer screening every year, women should still see their provider for a well-woman checkup.
Women who are at high risk for cervical cancer may need to be screened more often. Women at high risk might include those with HIV infection, organ transplant, or in-utero exposure to the drug DES. They should talk with their doctor or nurse for specific recommendations.
There is no approved screening test to find early signs of penile, vulvar, head-and-neck, or anal cancer. Routine examination of these areas and reporting of any changes to your provider is recommended. However, as previously mentioned, men who engage in receptive anal intercourse or women with cervical dysplasia or HIV 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 the 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 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. 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 decreases the occurrence of cervical and anal 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.
Resources for More Information
- CDC HPV Topic Site
- CDC Condom Effectiveness - Male Latex Condoms and Sexually Transmitted Diseases.
- McGill University HITCH Cohort Study.
- HPV.com, a website run by Merck, Inc., maker of one of the HPV vaccines.
- American Cancer Society. Cervical Cancer. 2017. Found at: https://www.cancer.org/cancer/cervical-cancer/about/key-statistics.html
- 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
- Centers for Disease Control and Prevention. HPV Information https://www.cdc.gov/hpv/index.html
- Centers for Disease Control and Prevention. How many cancers are linked with HPV each year? March, 2017. Found at: https://www.cdc.gov/cancer/hpv/statistics/cases.htm
- 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.
- FDA Access Data Cervarix. http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM186981.pdf
- FDA Access Data. Gardasil. http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM111263.pdf
- FDA Access Data. Gardasil 9. http://www.merck.com/product/usa/pi_circulars/g/gardasil_9/gardasil_9_pi.pdf
- 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.
- National Cancer Institute. HPV and Cancer. 2019. Retrieved from: https://www.cancer.gov/about-cancer/causes-prevention/risk/infectious-agents/hpv-fact-sheet
- National Cancer Institute. Human Papilomavirus Vaccines. 2018. Retrieved from: https://www.cancer.gov/about-cancer/causes-prevention/risk/infectious-agents/hpv-vaccine-fact-sheet
- 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.
- UCSF Anal Dysplasia Clinic website