Vanquishing HPV Related Cancers

What you need to know about Human Papiolloma Virus and the vaccines designed to prevent infection.

Vanquishing HPV Related Cancers

by C.H. Weaver M.D. 7/11/2016

Human papillomaviruses have a wide range of health effects, but vaccines continue to offer hope for prevention.

In 2008 Harald zur Hausen, DSc, MD, of Germany was awarded half the Nobel Prize in Physiology or Medicine for his pioneering work in the discovery of human papillomaviruses (HPV) as the primary cause of cervical cancer. Although a link with HPV seemed far-fetched when he began his research in the 1970s, work conducted by Dr. zur Hausen and others firmly established the relationship between HPV and cervical cancer and ultimately led to the development of HPV vaccines. Currently available vaccines have the potential to prevent an estimated 70 percent of all cervical cancers.

The story of HPV does not end there, however. Work continues on understanding the full range of HPV’s effects; in addition to contributing to cervical cancer, high-risk types of HPV have been linked with cancers of the vulva, vagina, penis, anus, and some cancers of the head and neck. Researchers also continue to monitor HPV vaccine safety and to explore whether use of the vaccine should be extended to additional segments of the population, such as boys. The ultimate goal: prevention of cancers that claim more than 300,000 lives worldwide each year.

An Overview of HPV

Human papillomaviruses consist of more than 100 different types. Some types of HPV cause warts on the hands or feet; others cause genital warts; and some have been linked with cancer, most notably cervical cancer.

The types of HPV that are linked with cervical cancer and genital warts are transmitted sexually. Genital HPV infection is extremely common and generally occurs soon after an individual becomes sexually active. The likelihood that an HPV infection will develop into cancer depends in part on the HPV type and the persistence of the infection. Certain types of HPV have been more strongly linked with cancer than others and are referred to as “high-risk.” HPV types 16 and 18, for example, are high-risk types that are thought to account for roughly 70 percent of all cases of cervical cancer. Among women infected with a high-risk type of HPV, persistent infection is the major risk factor for cervical cancer.

Infection with a high-risk type of HPV does not necessarily lead to cancer. Many infections disappear on their own,[1] and others may persist without causing cancer. Infection with a high-risk type of HPV does, however, increase the risk of cancer, and virtually all cases of cervical cancer can be linked to infection with a high-risk type of HPV. Among women infected with HPV, smoking appears to significantly increase the risk of cervical abnormalities,[2] providing yet another reason for women to avoid tobacco.

HPV Vaccines

Gardasil® (Quadrivalent Human Papillomavirus [types 6, 11, 16, 18] Recombinant Vaccine), and Cervarix,® are commercially available HPV vaccines intended to prevent infection with certain types of HPV; these vaccines do not treat existing HPV infections or cervical abnormalities. It’s also important to keep in mind that these vaccines do not protect against all types of HPV; women who are vaccinated should continue to be screened for cervical cancer.

Gardasil protects against HPV types 6 and 11 (which are linked to genital warts) as well as the cancer-associated types 16 and 18. The vaccine was approved in 2006 for use in girls and women between the ages of 9 and 26 years. Because the vaccine is not effective against existing infections, it is likely to have the greatest effect when given before a girl becomes sexually active. The Advisory Committee on Immunization Practices at the U.S. Centers for Disease Control and Prevention (CDC) recommends routine vaccination of girls 11 to 12 years of age.[3]

Since its licensure Gardasil has been featured prominently in the media, as scientists, healthcare providers, policy makers, and parents have discussed issues of the effectiveness, safety, and scope of vaccine recommendations. According to John Iskander, MD, MPH, associate director for science in the Immunization Safety Office of the CDC, such attention was not unexpected: “This vaccine was not only new but novel. It was targeting a sexually transmitted disease; it was targeting adolescents, who are not traditionally a major target for vaccines; and it was targeting cancer prevention. When you look at all of those factors together, it’s not surprising that it’s drawn this degree of interest.”

An issue of great importance to parents and girls is vaccine safety. The most common adverse events identified in prelicensure studies of Gardasil were pain at the injection site, swelling, redness, and fever.[4]The safety of Gardasil has also been closely monitored post-licensure using two primary sources: the Vaccine Adverse Event Reporting System (VAERS) and the Vaccine Safety Datalink (VSD). VAERS is managed jointly by the CDC and the FDA and collects reports about adverse events following vaccination. These reports come from many sources, including healthcare providers, patients, and parents. VAERS reports can neither prove nor disprove that vaccination caused a particular adverse event (some events follow vaccination but are not caused by vaccination), but the information reported to VAERS allows researchers to identify potential areas of concern that warrant additional investigation. The VSD links medical record information from several large managed-care organizations and allows researchers to conduct more in-depth analyses of potential safety concerns. “The overall findings so far from both systems, which we summarized for a major CDC advisory committee about four months ago, is that there have been no new serious, unexpected adverse events or safety concerns detected,” says Dr. Iskander.

In spite of these reassuring findings, a survey of healthcare providers found that some parents are still concerned that Gardasil is “too new.”[5] Asked to respond to this concern, Dr. Iskander explains, “Historically, most major safety concerns after vaccines are licensed show up within about the first 3 million doses or so. For example, with the first rotavirus vaccine and bowel obstruction, that showed up after about a million doses had been distributed. With Gardasil, I don’t have the exact numbers, but we’re past the 23-million-doses-distributed mark. At some point the argument of ‘it’s too new’ needs to be looked at a little more critically. In my almost 10 years working in vaccine safety, this is a very heavily studied vaccine.”

Something that parents may want to be aware of is the risk of fainting post-vaccination. Information from both VAERS and VSD suggests that fainting after vaccination is on the rise, particularly among adolescents. The main concern about fainting is that it could lead to injury as a result of falling. To address this concern, it is recommended that people of all ages be observed for 15 minutes after vaccination.[6]

The Burden of HPV-related Cancers

As HPV research has progressed, it’s become apparent that cervical cancer is just one piece of the puzzle. HPV has also been linked to other anogenital cancers (cancers of the vulva, vagina, penis, and anus) and with certain types of head and neck cancer. This suggests that the benefits of HPV vaccination could extend well beyond cervical cancer.

Cervical cancer is the most common HPV-related cancer. Worldwide there are an estimated 555,000 new diagnoses of cervical cancer each year and more than 300,000 deaths. More than 80 percent of these deaths occur in developing countries.[7] Cervical cancer is less common in the United States, where effective screening programs have led to the detection and the treatment of precancerous changes to the cervix, but there are still roughly 11,000 new diagnoses of cervical cancer in the United States each year.[8]

Noncervical cancers that have been linked with HPV include other anogenital cancers as well as oropharyngeal cancers. The oropharynx is the part of the throat that includes the soft palate, the base of the tongue, and the tonsils. Although many cases of oropharyngeal cancer can be attributed to smoking and alcohol use, it’s now apparent that some cases are caused by infection with high-risk types of HPV, particularly HPV 16.[9] The potential importance of HPV as a cause of oropharyngeal cancer is reflected in patterns of this cancer over time: although overall rates of head and neck cancer have declined as smoking rates have declined, rates of oropharyngeal cancer have not declined and appear to be increasing in young adults.[10] The way in which the oropharynx becomes infected with HPV remains uncertain, but sexual transmission appears likely.

In the United States, the total number of noncervical cancers caused by HPV is approximately the same as the total number of cervical cancers.[11] Furthermore, these noncervical HPV-related cancers are evenly divided between men and women, suggesting that approximately 25 percent of all HPV-related cancers in the United States occur in men. Because many of these cancers are thought to be caused by HPV types 16 and 18 (the HPV types included in current vaccines), vaccination may provide important benefits to both men and women. It must be remembered, however, that HPV vaccines have not yet been shown to be effective against oropharyngeal cancer, anal cancer, and penile cancer; a benefit of vaccination against these cancers is plausible but unconfirmed.

Other Conditions Caused by HPV

In addition to targeting HPV types 16 and 18, Gardasil prevents infection with HPV types 6 and 11, which account for most cases of genital warts. Although not life-threatening, genital warts can have profound psychological consequences and can be difficult and expensive to treat.[12]

HPV types 6 and 11 are also responsible for a less common but potentially serious condition known as recurrent respiratory papillomatosis (RRP).[13] RRP refers to benign (non-cancerous) growths in the upper airway that can interfere with breathing and speech. These growths can be surgically removed but often recur following treatment; as a result, patients with RRP often require multiple surgeries over the course of a lifetime to control the condition. RRP may develop in childhood (juvenile-onset RRP) or adulthood (adult-onset RRP). Children with RRP were most likely exposed to HPV types 6 or 11 in their mother’s genital tract during childbirth.

The Next Chapter

The work begun by Dr. zur Hausen in the 1970s continues today, as researchers expand our understanding of human papillomaviruses and their role in cancer and other diseases. This work may eventually broaden the use of currently available vaccines and could also lead to newer types of vaccines that protect against a wider range of HPV types. The result? Fewer cases of cervical cancer, certainly; but the impact of this research may extend well beyond that, ultimately improving the health of both women and men.

Finding Reliable Information About Vaccine Safety

This Web site from the U.S. Centers for Disease Control and Prevention provides regularly updated safety information for many vaccines, including HPV vaccines.

The Web site of the National Network for Immunization Information (NNii) provides information about a range of immunization topics, including how to find accurate vaccine information on the Internet. Parents may also be interested in the NNii booklet titled Do Vaccines Cause That?! A Guide for Evaluating Vaccine Safety Concerns.

Frequently Asked Questions

If I’m vaccinated, will I still need to be screened for cervical cancer?

Yes. The vaccine does not protect against all high-risk types of HPV. Average-risk women are advised to begin cervical cancer screening within three years of becoming sexually active and no later than the age of 21.[14] Screening generally includes a Pap test and may also include an HPV test.

Will Gardasil treat existing HPV infections?

No. The vaccine is intended to prevent infection with specific types of HPV. It will not treat existing infections or cervical abnormalities.

Can I become infected with HPV by being vaccinated?

No. The vaccine does not contain live virus and cannot cause infection.

What are the target age groups for vaccination?

The Advisory Committee on Immunization Practices recommends routine vaccination of girls ages 11 to 12 years. The vaccine can also be offered to girls as young as nine as well as girls and women between the ages of 13 and 26.

Is there any reason to vaccinate boys?

Although the vaccine is not yet licensed for use in boys, vaccinating boys may provide important benefits. Vaccinating boys would reduce transmission of the virus in the population and may also protect boys against HPV-related conditions such as genital warts and cancers of the penis, anus, and oropharynx. The vaccine may be licensed for use in boys after more data become available.

How many doses of the vaccine are required?

The vaccine is given in three doses over a six-month period.

References

[1] Ho GY, Bierman R, Beardsley L, Chang CJ, Burk RD. Natural history of cervicovaginal papillomavirus infection in young women. New EnglandJournal of Medicine. 1998;338(7):423-28.

[2] Wang SS, Zuna RE, Wentzensen N, et al. Human papillomavirus cofactors by disease progression and human papillomavirus types in the Study to Understand Cervical Cancer Early Endpoints and Determinants. Cancer Epidemiology, Biomarkers, and Prevention. 2009;18(1):113-20.

[3] Markowitz LE, Dunne EF, Saraiya M, et al. Quadrivalent human papillomavirus vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. 2007;56(RR-2):1-24.

[4] Gardasil® Prescribing Information. Merck Web site. Available at: . Accessed April 8, 2009.

[5] Advisory Committee on Immunization Practices. Minutes of the October 2008 meeting. Centers for Disease Control and Prevention Web site. Available at: . Accessed April 8, 2009.

[6] Kroger AT, Atkinson WL, Marcuse EK, et al. General recommendations on immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. 2006;55(RR-15):1-48.

[7] Global Cancer Facts & Figures 2007. American Cancer Society Web site. Available at: . Accessed April 8, 2009.

[8] Cancer Facts & Figures 2008. American Cancer Society Web site. Available at: . Accessed April 8, 2009.

[9] Ryerson AB, Peters ES, Coughlin SS, et al. Burden of potentially human papillomavirus-associated cancers of the oropharynx and oral cavity in the US, 1998-2003. Cancer. 113(10 Suppl):2901-9.

[10] Sturgis EM, Cinciripini PM. Trends in head and neck cancer incidence in relation to smoking prevalence: An emerging epidemic of human papillomavirus-associated cancers? Cancer. 2007;110(7):1429-35.

[11] Gillison ML, Chaturvedi AK, Lowy DR. HPV prophylactic vaccines and the potential prevention of noncervical cancers in both men and women. Cancer. 2008;113(10 Suppl):3036-46.

[12] Lacey CJ, Lowndes CM, Shah KV. Chapter 4: Burden and management of non-cancerous HPV-related conditions: HPV-6/11 disease. Vaccine. 2006;24(3 Suppl:S3/35-S3/41.

[13] Lacey CJN, Lowndes CM, Shah KV. Chapter 4: Burden and management of non-cancerous HPV-related conditions: HPV-6/11 disease. Vaccine. 2006;24(3 Suppl):S35-S41.

[14] Smith RA, Cokkinides V, Brawley OW. Cancer screening in the United States, 2008: A review of current American Cancer Society guidelines and cancer screening issues. CA: A Cancer Journal for Clinicians. 2008;58(3);161-79.

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