cervical cancer

HPV vaccines: Research on safety, racial disparities in vaccination rates and male participation

Source: journalistsresource.us1.list-manage.com
Author: staff

Since it became available in the United States in 2006, the Human Papillomavirus (HPV) vaccine has been a source of debate, with proponents lauding it as a substantial gain in the fight against cancer, and opponents concerned with its implications for sexual activity among youth. With the U.S. Food and Drug Administration’s recent approval of Gardasil-9 — a vaccine that protects against nine of the most common strains of HPV that account for approximately 90 percent of cervical, vulvar, vaginal and anal cancers — there is both a renewed interest and concern that calls for a nuanced and comprehensive review of the science.

HPV is the most common sexually transmitted infection in the United States, with nearly all sexually active men and women believed to contract at least one form of it during their lifetime. According to the U.S. Centers for Disease Control and Prevention (CDC), an estimated 79 million Americans have HPV, and about 14 million become newly infected annually. While most infections clear the body within two years, some can persist and result in genital warts, cervical cancer or other types of cancers in men and women. Of the many HPV strains that exist, HPV types 16 and 18 have been identified as high risk, accounting for about 70 percent of all cervical cancer, as well as a large proportion of other HPV-related cancers.

While cervical cancer was previously a leading cause of death among women in the U.S., death rates declined substantially after the introduction of the Pap test in the 1950s. Nevertheless, according to the CDC, more than 12,000 women in the U.S. are diagnosed with cervical cancer each year, and more than 4,000 die from it. Public discourse around HPV tends to focus on the health of women because they disproportionately bear the burden of its health consequences. However, men also face substantial risk, particularly as it relates to oral and anal cancers.

Although screening procedures are in place for early detection of cervical cancer, there are no comparable strategies to identify HPV-related cancer in its early stages for men. Consequently, the administration of a vaccine to prevent infection and transmission presents an important line of protection. Currently, the HPV vaccine is administered over a course of three injections, which must be completed within six months to confer full protection. A 2012 review of clinical trials of HPV vaccines shows that vaccines designed to protect against two or four of the most common strains have very high efficacy rates, ranging between 90 percent and 100 percent. For that reason, large public health efforts have focused on improving vaccination rates before boys and girls become sexually active.

Today, both the CDC and American Academy of Pediatrics recommend routine vaccination against HPV for all 11-year-olds and 12-year-olds in the U.S. Although the early age of vaccination has been a source of public debate, medical recommendations are based partly on evidence that shows that antibody responses are highest during this age period. Also, it is a good idea to vaccinate adolescents before they come into contact with the virus as the vaccine is not effective against HPV types that already have been acquired. Despite such recommendations from medical professionals, vaccination completion rates remain low — 40 percent for girls and 20 percent for boys in 2014. That is substantially lower than the vaccination rate for tetanus, diphtheria, and pertussis and the vaccination rate for meningitis among members of the same age group.

Below are a series of studies that will help journalists understand and explain this important health topic from a variety of angles, including vaccine safety and racial and gender disparities in vaccination rates. Beat reporters can find related reports and statistics from organizations such as the CDC, National Cancer Institute and World Health Organization.

__________________________

Barriers to vaccination

“Reasons for Not Vaccinating Adolescents: National Immunization Survey of Teens, 2008-2010”
Darden, P.M.; et al. Pediatrics, April 2013, Vol. 131. doi: 10.1542/peds.2012-2384.

Summary: Using data from the National Immunization Survey of Teens, researchers found that parental intentions to not vaccinate for HPV increased from 39.8 percent in 2008 to 43.9 percent in 2010. The most commonly cited reasons for not vaccinating were “not recommended/needed,” “not sexually active,” and “safety concerns/side effects.” Vaccine safety concerns increased from 4.5 percent in 2008 to 16.4 percent in 2010.

“Barriers to Human Papillomavirus Vaccination Among US Adolescents: A Systematic Review of the Literature”
Holman, D.M.; et al. JAMA Pediatrics, January 2014, Vol. 168. doi: 10.1001/jamapediatrics.2013.2752.

Summary: “Health care professionals cited financial concerns and parental attitudes and concerns as barriers to providing the HPV vaccine to patients. Parents often reported needing more information before vaccinating their children. Concerns about the vaccine’s effect on sexual behavior, low perceived risk of HPV infection, social influences, irregular preventive care, and vaccine cost were also identified as potential barriers among parents.”

Vaccine safety

“Adverse Events Following Immunization in Ontario’s Female School-Based HPV Program”
Harris, T.; Williams, D.M.; Feiurek, J.; Scott, T.; Deeks, S.L. Vaccine, January 2014, Vol. 32. doi: 10.1016/j.vaccine.2014.01.004.

Summary: After a school-based HPV vaccination program was implemented among eighth grade girls in Ontario, Canada, researchers analyzed reports of adverse events following immunization over the following four years. From 2007 to 2011, nearly 700,000 HPV vaccine doses were administered and 133 confirmed cases of adverse events were reported. The most commonly reported side effects included allergic reactions (25 percent), rashes (22 percent), reactions at the injection site (20 percent), and non-specific “other events” (26 percent). Ten serious cases were identified, which included two cases of anaphylaxis, two seizures, one thrombocytopenia, and one death, which was concluded by the coroner to be due to a previously undiagnosed cardiac condition. Ultimately, the researchers conclude that the findings are in line with existing evidence on the safety profile of the HPV vaccine, and no new safety concerns were identified.

“Safety of Human Papillomavirus Vaccines: A Review”
Macartney, K.K.; Chiu, C.; Georgousakis, M.; Brotherton, J.M.L. Drug Safety, June 2013, Vol. 36. doi: 10.1007/s40264-013-0039-5.

Abstract: “Both vaccines are associated with relatively high rates of injection site reactions, particularly pain, but this is usually of short duration and resolves spontaneously. Systemic reactions have generally been mild and self-limited. Post vaccination syncope has occurred, but can be avoided with appropriate care. Serious vaccine-attributable adverse events, such as anaphylaxis, are rare, and although not recommended for use in pregnancy, abnormal pregnancy outcomes following inadvertent administration do not appear to be associated with vaccination. HPV vaccines are used in a three-dose schedule predominantly in adolescent females: as such, case reports linking vaccination with a range of new onset chronic conditions, including autoimmune diseases, have been made. However, well-conducted population-based studies show no association between HPV vaccine and a range of such conditions.”

Disparities in vaccination rates

“Racial/Ethnic and Poverty Disparities in Human Papillomavirus Vaccination Completion”
Niccolai, L.M.; Mehta, N.R.; Hadler, J.L. American Journal of Preventive Medicine, October 2011, Vol. 41. doi: 10.1016/j.amepre.2011.06.032.

Abstract: “Data from the 2008-2009 National Immunization Survey-Teen for girls aged 13-17 years who received at least one dose of HPV vaccine (n=7606) were analyzed in 2010-2011. During this 2-year period, 55 percent of adolescent girls who initiated vaccination completed the three-dose series. Completion was significantly higher in 2009 (60 percent) compared to 2008 (48 percent; p<0.001). After controlling for covariates, adolescents who were black or Hispanic were significantly less likely to complete vaccination than whites. Adolescents living below the federal poverty level were significantly less likely to complete vaccination than adolescents with household incomes >$75,000.”

“Social Inequalities in Adolescent Human Papillomavirus (HPV) Vaccination: A Test of Fundamental Cause Theory”
Polonijo, A.N.; Carpiano, R.M. Social Science & Medicine, April 2013, Vol. 82. doi: 10.1016/j.socscimed.2012.12.020.

Abstract: “Analyses of 2008, 2009, and 2010 United States National Immunization Survey-Teen data (n = 41,358) reveal disparities particularly for vaccine knowledge and receipt of a health professional recommendation. While parental knowledge is a prerequisite to adolescent vaccine uptake, low socioeconomic status (SES) and racial/ethnic minority parents have significantly lower odds of knowing about the vaccine. Receipt of a health professional’s recommendation to vaccinate is strongly associated with vaccine uptake, however the odds of receiving a recommendation are negatively associated with low SES and black racial/ethnic status.”

“Sociodemographic Differences in Human Papillomavirus Vaccine Initiation by Adolescent Males”
Agawu, A.; et al. Journal of Adolescent Health, November 2015, Vol. 57. doi: 10.1016/j.jadohealth.2015.07.002.

Summary: Researchers studied patterns of HPV vaccination among a sample of 58,757 adolescent males between the ages of 11 and 18 in a large primary care network. Results showed that African American males with private health insurance were twice as likely to initiate vaccination than White males with private insurance, while African American males on Medicaid were nearly three times more likely. Similar trends were observed among Hispanic males. The authors conclude that, “although the true mechanism underlying these differences remains unknown, potential candidates include provider recommendation patterns and differential vaccine acceptance within these groups.”

HPV vaccine and young males

“HPV Vaccination Coverage of Male Adolescents in the United States”
Lu, P.J.; et al. Pediatrics, October 2015, Vol. 136. doi: 10.1542/peds.2015-1631.

Summary: Researchers used data from the 2013 National Immunization Survey-Teen to investigate trends in HPV vaccination of adolescent boys. Findings revealed low rates of both vaccine uptake (34.6 percent) and completion (13.9 percent), however African American and Hispanic males were more likely to receive the vaccine than their White peers. In order to improve vaccination coverage, the authors conclude that a comprehensive approach is needed which includes physicians regularly assessing their patient’s vaccination status, educating doctors about current HPV vaccine recommendations as well as information on vaccine efficacy and safety, reducing costs, and improving health communication strategies to dispel misinformation about the vaccine.

“Longitudinal Predictors of Human Papillomavirus Vaccination Among a National Sample of Adolescent Males”
Reiter, P.L.; et al. American Journal of Public Health, August 2013, Vol. 103. doi: 10.2105/AJPH.2012.301189.

Abstract: “In fall 2010 and 2011, a national sample of parents with sons aged 11 to 17 years (n = 327) and their sons (n = 228) completed online surveys to identify predictors of HPV vaccination. Only 2 percent of sons had received any doses of HPV vaccine at baseline, with an increase to 8 percent by follow-up. About 55 percent of parents who had ever received a doctor’s recommendation to get their sons HPV vaccine did vaccinate between baseline and follow-up, compared with only 1 percent of parents without a recommendation. Willingness to get sons the HPV vaccine decreased from baseline to follow-up among both parents and sons.”

“Acceptability of Human Papillomavirus Vaccine for Males: A Review of the Literature”
Liddon, N.; Hood, J.; Wynn, B.A.; Markowitz, L.E. Journal of Adolescent Health, February 2010, Vol. 46. doi:10.1016/j.jadohealth.2009.11.199.

Abstract: “Among mothers of sons, support of HPV vaccination varied widely from 12 percent to 100 percent, depending on the mother’s ethnicity and type of vaccine, but was generally high for a vaccine that would protect against both genital warts and cervical cancer. Health providers’ intention to recommend HPV vaccine to male patients varied by patient age but was high (82 percent-92 percent) for older adolescent patients. A preference to vaccinate females over males was reported in a majority of studies among parents and health care providers. Messages about cervical cancer prevention for female partners did not resonate among adult males or parents. Future acceptability studies might incorporate more recent data on HPV-related disease, HPV vaccines, and cost-effectiveness data to provide more current information on vaccine acceptability.”

“Parents’ Decisions About HPV Vaccine for Sons: The Importance of Protecting Sons’ Future Female Partners”
Schuler, C.L.; DeSousa, N.S.; Coyne-Beasley, T. Journal of Community Health, October 2014, Vol. 39. doi: 10.1007/s10900-014-9859-1.

Abstract: “76 percent of parents reported vaccine decisions for sons were likely to be influenced by preventing HPV transmission from sons to their female partners. Parents likely to be influenced by female partner protection in vaccine decisions had greater intention to vaccinate sons than their counterparts (adjusted odds ratio 2.54). Because parents likely to consider female partners had increased intention to vaccinate sons, future efforts to improve vaccine uptake in boys should explore the benefits of highlighting potential female partner protection, as this concept may resonate with many parents.”

January, 2016|Oral Cancer News|

Expanded age indication cleared for Gardasil 9 in males

Source: www.FormularyJournal.ModernMedicine.com
Author: Erin Bastick
 

FDA approved an expanded age indication for Human Papillomavirus 9-valent Vaccine, Recombinant (Gardasil 9, Merck) in males.

Seven HPV types in Gardasil 9 (HPV 16, 18, 31, 33, 45, 52, and 58) cause approximately 90% to 95% of HPV-related anal cancers, 90% of cervical cancers, and 80% of high-grade cervical lesions worldwide.These 7 types also cause the majority of HPV-related vulvar and vaginal cancers. Gardasil 9 includes the greatest number of HPV (Human Papillomavirus) types of any available HPV vaccine.

Gardasil 9 was previously approved for use in girls and young women aged 9 to 26 years for the prevention of cervical, vulvar, vaginal, and anal cancers caused by HPV 16, 18, 31, 33, 45, 52, and 58, precancerous or dysplastic lesions caused by HPV 6, 11, 16, 18, 31, 22, 45, 52, and 58, and genital warts caused by HPV types 6 and 11. As for use in male patients, the vaccine was previously approved for use in boys aged 9 to 15 years for the prevention of anal cancer caused by HPV types 16, 18, 31, 33, 45, 52, and 58, precancerous or dysplastic lesions caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58.

With the newest approval, Gardasil 9 is now also indicated for use in males aged 16 to 26 years for the prevention of these diseases. According to the CDC, HPV vaccination rates are unacceptably low compared to rates for other adolescent vaccines, and vaccination coverage in males is especially low in males. The approval of the expanded age indication in male patients was based on results from a clinical trial program for Gardasil 9 that was designed to build upon the safety and efficacy established in clinical trials with Gardasil [Human Papillomavirus Quadrivalent (types 6, 11, 16, and 18) Vaccine, Recombinant].

“Any health plans that have not yet made a decision regarding coverage for Gardasil 9 for males 16-26 can do so now that that the vaccine is indicated in this population,” according to a company statement from Merck. “Most managed care plans have already made decisions to cover the cost of Gardasil 9, including for males 16 through 26 years of age, making the number of plans covering Gardasil 9 similar to the number covering the cost of Gardasil. The approval of Gardasil 9 for males 16 through 26 years of age is a milestone in the planned transition from Gardasil to Gardasil 9, as both products are now approved for the same populations.”

The most common adverse reactions associated with the use of Gardasil 9 in males aged 16 to 26 years included injection-site pain, swelling, and erythema. Not all vulvar, vaginal and anal cancers are caused by HPV; Gardasil 9 only protects against those cancers caused by HPV 16, 18, 31, 33, 45, 52, and 58. Gardasil 9 is contraindicated in individuals with hypersensitivity, including severe allergic reactions to yeast, or after a previous dose of Gardasil 9 or Gardasil.

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

December, 2015|Oral Cancer News|

A cancer on the rise, and the vaccine too late for Gen X

Source: www.cnn.com
Author: Martha Shade
 
151014135224-generation-x-hpv-graphic-exlarge-169

(CNN)The vaccine given to prevent cervical cancer in women could end up saving men’s lives, too.

Evidence is mounting that the HPV vaccine is also effective in preventing other HPV-related cancers, including those of the head and neck. Although most people who get HPV do not develop cancer, rates of HPV-related head and neck cancers are dramatically rising for men aged 40 to 50, according to Dr. Maura L. Gillison, the Jeg Coughlin Chair of Cancer Research at the Ohio State University Comprehensive Cancer Center.

When Gillison recently gave a presentation showing the increasing rate of HPV-related head and neck cancer among men, her audience was shocked. “I’ve never shown a slide where the audience gasps,” she said.

Related: Yes, oral sex can lead to cancer

“The risk of getting this cancer is strongly related to when you were born. If you are currently a 40- to 45-year-old man, your risk of getting this cancer is dramatically higher than a 40- to 45-year-old man three or four decades ago,” Gillison said.

Today’s 40- to 50-year-old men have had more sexual partners and have engaged in more oral sex than previous generations, according to experts, significantly raising their risk of an HPV-related head and neck cancer.

Actor Michael Douglas made headlines in 2013 when he announced he was battling an HPV-related cancer and that he got it from performing oral sex. Douglas was 68 when he was diagnosed, but many of the men being diagnosed with these HPV-related cancers are much younger.

What’s a Gen X’er to do?

HPV is usually acquired when young. It can lay dormant, and most oropharyngeal cancer (a type of head and neck cancer) is diagnosed decades later, beginning around age 40 to 50. And the more partners you have, the greater your risk.

HPV vaccines weren’t recommended and approved in the United States until 2006. And the vaccine was not even recommended for boys until 2011.

So what’s an aging Gen X’er to do?

“You’re starting to get colonoscopies; you’re starting to get checked for prostate cancer. This is one more thing to add to that list that you really have to watch for,” said Brian Hill, founder of the Oral Cancer Foundation.

Warning signs of HPV-related head and neck cancer

• Persistent lump on neck

• Persistent earache on one side

• Swelling or lump in the mouth

• Chronic sore throat

• Difficult or painful swallowing

• Change in voice

Source: Oral Cancer Foundation, Dr. Carole Fakhry

Symptoms of HPV-related head and neck cancer include a change in voice, a sore throat that doesn’t go away, an earache on one side and difficult or painful swallowing.

Hill’s story is typical: His doctors initially assumed he had an enlarged lymph node due to an infection. Two doctors gave him antibiotics before he was diagnosed with late-stage oropharyngeal cancer. His experience led him to form the Oral Cancer Foundation.

Finding the disease at an early stage is lifesaving. When it’s diagnosed early, these HPV-related cancers are survivable, according to Dr. Carole Fakhry of the Johns Hopkins Head & Neck Cancer Center. “If you have a lump in your neck, make sure to get checked.

“A very common story is: ‘I was shaving and I noticed this lump in my neck,” she said. “And he goes through two or three rounds of antibiotics and then someone finally thinks about cancer.”

‘Dental hygienists are becoming the best screeners’

Traditionally, cancers of the head and neck were often linked to alcohol or smoking, and these non-HPV cancers tend to be located at the front of the mouth and the voice box. Incidence of these cancers are dropping.

“The truth of the matter is that smoking-related cancers are declining,” Fakhry said. “On the other hand, cancers related to HPV are increasing.”

HPV-related cancers usually originate in the back of the mouth. “Most of these cancers are tonsils and back-of-tongue cancers,” she said. “Tonsils are basically these crypts, and tumors grow deep within these crypts, so these tumors can be hard to find.”

Since tumors are often hidden, dentists and dental hygienists are becoming the first line of attack. Men may also be more likely to visit a dentist regularly than a doctor, according to Hill.

“Dental hygienists are becoming the best screeners for this. They’re becoming the point at the end of the spear when it comes to screening and finding abnormalities,” he said.

Dentists and hygienists are encouraged to look for telltale signs of HPV-related cancer: asymmetrical or swollen tonsils, or a lesion in the back of the throat. But these cancers are notoriously tough to spot and tend to be diagnosed after patients develop a lump in the neck.

So what can you do?

“Make sure you get your kids vaccinated (for HPV),” Fakhry said.

Dr. Dan Beachler, lead author of a new study that found further evidence the HPV vaccine protects against multiple types of HPV-related cancers, agrees: “We still don’t know that much about oral HPV. Primary prevention through vaccination might have the most potential.”

Besides the cervix and the head and neck, some strains of HPV can also lead to cancer of the anus, penis and vulva.

A preventive HPV vaccine is most effective when given to children before they become exposed to HPV. The three dose series is recommended at age 11 or 12.

Initially recommended just for girls, the Centers for Disease Control and Prevention now recommends that boys be vaccinated, too. In addition, vaccination is recommended through the age of 26 in women and through age 21 in men who were not vaccinated previously.

“Young people do not avoid oral sex. That being a given, the best thing we can do is increase the vaccination rate. The second thing we can do is be highly aware of signs and symptoms,” Hill said.

And don’t panic. Although HPV-related cancers are on the rise, they’re still uncommon.

“Even though the rates are dramatically increasing, it’s still a relatively rare cancer. We don’t want to create a panic. We just want to raise awareness,” Gillison said.

Manitoba expands HPV vaccination program to include boys

Source: www.rapidnewsnetwork.com
Author: Cody Griffin
 
Human-papillomavirus-HPV-va

While most HPV infections go away over time with no treatment, a few can go on to cause cancer.

Health Minister Sharon Blady said the province’s vaccine program will be expanded next year to include Grade 6 and Grade 9 boys as part of Manitoba’s cancer strategy.

The province will also be doing a catch-up period in grade 9. About 59 percent of the physicians recommended HPV vaccination more often for adolescents who they perceived to be at higher risk for getting an HPV infection, as opposed to recommending it routinely for all adolescents.

“Human papillomavirus can cause abnormal cell changes that can lead to cervical cancer, as well as cancer of the vagina, vulva, penis, anus, mouth and throat”, said Dr. Sri Navaratnam, president and CEO, CancerCare Manitoba.

A study in Texas found that a more rigorous, information driven outreach program increased the number of children receiving the vaccine, and other recent studies have reinforced the efficacy of the vaccine to prevent cancer and not promote promiscuity among teenagers.

Any girl or boy who misses the vaccine in Grade 6 will be eligible to get it in later years free of charge under the province’s “once eligible, always eligible”, program. But now we know it causes cancer in men as well.

Gilkey and colleagues found that 27 percent of physicians across the country reported that they do not strongly endorse HPV vaccination, and 26 percent and 39 percent reported that they do not provide timely recommendations for vaccinating girls and boys, respectively.

“The vaccine’s definitely most effective when you’re younger because you have A better immune response to vaccines and when you haven’t been exposed to the virus yet”, he said.

Routledge also said parents will need to give consent for their kids to receive the shot.

Saskatchewan Health Minister Dustin Duncan says offering the HPV vaccine for free to boys is something the province is looking at. “Vaccinating boys with the HPV vaccine will help prevent transmission of the virus and help reduce the incidence and mortality of all HPV-related cancers”. Nova Scotia has announced it plans to do the same.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

October, 2015|Oral Cancer News|

Multisite HPV16/18 Vaccine Efficacy Against Cervical, Anal, and Oral HPV Infection

Source: www.oxfordjournal.com
Authors: Daniel Bleacher, Aimee Kreimer, Mark Schiffman, Rolando Herrero, Ana Cecilia Rodriguez, Douglas Lowy, Carolina Porras, John Schiller, Wim Quint, Silvia Jiminez, Mahboobeh Safaeian, Linda Struijk, John Scchussler, Allan Hildesheim, Paula Gonzalez

 

Background: Previous Costa Rica Vaccine Trial (CVT) reports separately demonstrated vaccine efficacy against HPV16 and HPV18 (HPV16/18) infections at the cervical, anal, and oral regions; however, the combined overall multisite efficacy (protection at all three sites) and vaccine efficacy among women infected with HPV16 or HPV18 prior to vaccination are less known.

Methods: Women age 18 to 25 years from the CVT were randomly assigned to the HPV16/18 vaccine (Cervarix) or a hepatitis A vaccine. Cervical, oral, and anal specimens were collected at the four-year follow-up visit from 4186 women. Multisite and single-site vaccine efficacies (VEs) and 95% confidence intervals (CIs) were computed for one-time detection of point prevalent HPV16/18 in the cervical, anal, and oral regions four years after vaccination. All statistical tests were two-sided.

Results: The multisite woman-level vaccine efficacy was highest among “naïve” women (HPV16/18 seronegative and cervical HPV high-risk DNA negative at vaccination) (vaccine efficacy = 83.5%, 95% CI = 72.1% to 90.8%). Multisite woman-level vaccine efficacy was also demonstrated among women with evidence of a pre-enrollment HPV16 or HPV18 infection (seropositive for HPV16 and/or HPV18 but cervical HPV16/18 DNA negative at vaccination) (vaccine efficacy = 57.8%, 95% CI = 34.4% to 73.4%), but not in those with cervical HPV16 and/or HPV18 DNA at vaccination (anal/oral HPV16/18 VE = 25.3%, 95% CI = -40.4% to 61.1%). Concordant HPV16/18 infections at two or three sites were also less common in HPV16/18-infected women in the HPV vaccine vs control arm (7.4% vs 30.4%, P < .001).

Conclusions: This study found high multisite vaccine efficacy among “naïve” women and also suggests the vaccine may provide protection against HPV16/18 infections at one or more anatomic sites among some women infected with these types prior to HPV16/18 vaccination.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

October, 2015|Oral Cancer News|

Vaccine clears some precancerous cervical lesions in clinical trial

Source: www.sciencedaily.com
Author: Mark L Bagarazzi, MD et al.
 

Scientists have used a genetically engineered vaccine to successfully eradicate high-grade precancerous cervical lesions in nearly one-half of women who received the vaccine in a clinical trial. The goal, say the scientists, was to find nonsurgical ways to treat precancerous lesions caused by HPV.

“Every standard therapeutic option for women with these lesions destroys part of the cervix, which is particularly relevant for women of childbearing age, who may then be at risk for preterm birth due to a weakened cervix,” says Cornelia Trimble, M.D., professor of gynecology and obstetrics, oncology, and pathology at the Johns Hopkins University School of Medicine, and first author of the new report, which appears online Sept. 17 in The Lancet. “A vaccine able to cure precancerous lesions could eventually be one way women can avoid surgery that is invasive and can also harm their fertility.”

High-grade cervical lesions, termed CIN2/3, occur most often in women 40 or younger, according to Trimble, a member of Johns Hopkins’ Kelly Gynecologic Oncology Service and Kimmel Cancer Center. Because the lesions can progress to cancer, they are usually removed by surgery, freezing or laser. The procedures are successful in removing the precancerous areas in approximately 80 percent of women, says Trimble. Less troublesome lesions, called low-grade dysplasia, are usually monitored by physicians rather than immediately removed because they pose less of a risk for cancer and usually regress on their own.

For the study, the scientists used a vaccine, originally developed by University of Pennsylvania scientist David Weiner, Ph.D., which is engineered to teach immune system cells to recognize precancerous and cancerous cells. Those cells are coated with proteins linked to an infection with two strains of HPV — 16 and 18 — that cause cervical cancer. The vaccine, given by injection into the arm, is made by Inovio Pharmaceuticals Inc., which funded the clinical trial, and whose employees co-authored the report with Trimble.

Between 2011 and 2013, the scientists recruited 167 women, ages 18 to 55, with newly diagnosed, high-grade precancerous cervical lesions. The women were randomly assigned to receive either three doses of the vaccine or saline injections over a 12-week period at 36 hospitals and private gynecology practices in the U.S. and six other countries.

After each of the injections, the scientists gave the women a small electric pulse at the site of the injection. Cells near the electric pulse open their pores, says Trimble, increasing the likelihood that the vaccine will be taken up by immune system cells.

Of 114 women who received at least one vaccine dose, 55 (48.2 percent) had a regression of their precancerous lesion, meaning their lesions disappeared or converted to low-grade lesions, compared with 12 of 40 (30 percent) who received saline injections. Of the 114, 107 received all three vaccine doses, and 53 of them (49.5 percent) had regression of their lesions. Of the 40 in the saline group, 36 got all three injections, and 11 of them (30.6 percent) had regression of their lesions. Thirteen women dropped out of the study after enrollment.

Two patients discontinued the study because of pain at the injection site. Skin redness was more common in the vaccine group compared with saline.

Among women who completed all three injections, scientists could find no trace of HPV in the cervixes of 56 of the 107 women who received the vaccine, compared with only nine of 35 saline recipients.

“In many of these women, the vaccine not only made their lesions disappear, but it also cleared the virus from their cervix,” says Trimble. “In most unvaccinated patients whose lesions went away, the virus was still present, and many still had low-grade lesions.”

Trimble says clearance of the virus is a “significant bonus” from receiving the vaccine because persistent HPV infection is a major risk factor for recurrence of cervical lesions.

After 12 weeks, doctors surgically removed lesions that did not regress and took biopsies of each study participant’s cervix. In the surgically removed lesions, scientists found miniscule cancers in two of the women who received the vaccine. Trimble says these microinvasive cancers are rarely diagnosed by a biopsy but are found in surgical specimens.

n the biopsy samples, the scientists found that patients whose lesions completely regressed after treatment had more immune cells, called T cells, present in the tissue. “It’s important that T cells capable of recognizing HPV stay in the cervix and fight off any recurrence of the infection,” says Trimble.

“This is a great first step,” says Trimble. “We showed that the vaccine may enable an immune response in a person whose immune system was initially not adequately engaged or was hampered in some way so as to let the lesion occur.”

Trimble says that precancerous lesions are unlikely to progress to cancer during the vaccine treatment period, and monitoring of high-grade lesions is done routinely for pregnant women. “It typically takes about 10 or more years for precancerous cells to become cancer, so there is a window of opportunity to intervene with nonsurgical approaches to reverse the process of viral-associated cancers,” says Trimble.

Trimble says she and her colleagues are now working to identify biomarkers from cervical tissue that can predict which lesions are more likely to persist and eventually progress to cancer. The research team will be monitoring this initial group of study participants to see whether they have fewer recurrences than unvaccinated patients. Trimble is also studying other types of vaccines to prevent the progression of high-grade cervical lesions to cancer.

####

Trimble received an unrestricted grant from Inovio Pharmaceuticals Inc., but she has no other financial or consulting arrangements with the company.

In addition to Trimble, scientists who contributed to the research include Lance Edwards from Suffolk Obstetrics and Gynecology in Port Jefferson, New York; R. Lamar Parker from Lyndhurst Gynecologic Associates in Winston-Salem, North Carolina; Lynette Denny from the University of Cape Town’s Groote Schuur Hospital in South Africa; David B. Weiner from the University of Pennsylvania; and Matthew P. Morrow, Kimberly A. Kraynyak, Xuefei Shen, Michael Dallas, Jian Yan, Mary Giffear, Ami Shah Brown, Kathleen Marcozzi-Pierce, Divya Shah, Anna M. Slager, Albert J. Sylvester, Amir Khan, Kate E. Broderick, Robert J. Juba, Timothy A. Herring, Jean Boyer, Jessica Lee, Niranjan Y. Sardesai, David B. Weiner and Mark L Bagarazzi from Inovio Pharmaceuticals Inc.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

September, 2015|Oral Cancer News|

AstraZenica, Inovio strike deal to find HPV cancer vaccine

Source: www.philly.com
Author: David Sell
 

Local drugmakers – big and small – struck a deal to try to develop a vaccine to prevent a form of cervical, head and neck cancer.

 MedImmune, which is the biologics and research division with AstraZeneca, said Monday it will collaborate with Inovio Pharmaceuticals to develop an early stage cancer vaccine designed to treat human pappilomavirus.

 AstraZeneca will pay Inovio $27.5 million upfront. If the compound reaches development and commercial milestones, Inovio could get up to $700 million, along with “double-digit tiered royalties” on product sales. However, sales are a long way off because the compound is only in phase I and phase II of what is normally a three-phase clinical trial process.

 AstraZeneca is moving its headquarters from London to Cambridge in the United Kingdom, and has operations in Wilmington and Fort Washington. The MedImmune division is headquartered in Gaithersburg, Md.

 Inovio is based in Blue Bell and its basic scientific premise is to use DNA to develop vaccines. unlike most current vaccines.

 The companies have worked together before. The compound at the heart of the latest deal is called INO-3112. The early clinical trials are examining cervical and head and neck camcers and the compound tries to generate “killer T-cell responses that are able to destroy HPV 16- and 18- driven tumors. These HPV types are responsible for more than 70 per cent of cervical pre-cancers and cancers, ” according to the statement.

The full statement from AstraZeneca is here.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

August, 2015|Oral Cancer News|

Professor Harald zur Hausen: Nobel scientist calls for HPV vaccination for boys

Source: www.independent.co.uk
Author: Charlie Cooper & Gloria Nakajubi
 

The UK should vaccinate all boys against the cancer-causing human papilloma virus (HPV), the Nobel Prize-winning scientist who discovered the link between HPV and cancer has said.

Professor Harald zur Hausen, the German virologist whose theory that HPV could be a cause of cervical cancers led to global efforts to vaccinate girls against the virus, said that boys should also be protected.

There is now a wealth of evidence that HPV also causes cancers in men, including anal, penile and throat cancer. Professor zur Hausen added that there was now a chance to “eradicate” HPV viruses altogether if the world developed global vaccination programmes for all children.

Since 2008 the UK has offered free vaccinations against HPV to girls aged 12 to 13 – a programme that had an almost 87 per cent uptake from 2013 to 2014 and has led to falls in the number of pre-cancerous abnormalities of the cervix, according to research carried out among vaccinated girls in Scotland.

Capture

Vaccine authorities in the UK, traditionally an international leader in the field of immunisation, are yet to make a judgement on a publicly funded vaccination programme for boys, which would follow in the wake of those already in place in Australia, Austria, Israel and parts of Canada.

HPV is the name for a common group of viruses that can affect the moist membranes of the cervix, anus, mouth and throat. It is usually spread through sexual contact.

Most sexually active people will contract it in their lifetime but usually it causes no ill-effects. However, in some cases it causes changes to cells, which can become cancerous. It is the cause of almost all cases of cervical cancer, a discovery made by Professor zur Hausen in the 1970s, for which he won the Nobel Prize in physiology or medicine in 2008.

Speaking to HPV Action, in an interview to be published by the campaign group this week, Professor zur Hausen said that vaccinating boys was of “the utmost importance”, not only because boys can also contract HPV-related cancers of the throat, anus and penis, but because protecting boys is key to ending transmission of the virus altogether.

“The vaccination programme for girls [in the UK] is marvellous – it reaches a very high proportion,” he said. “In my opinion, the vaccination of boys is also of the utmost importance because virus transmission is due to male partners and men are affected by oropharyngeal [cancers of the throat], anal and penile cancers as well as genital warts.”

Last year the UK’s vaccination authority, the Joint Committee on Vaccination and Immunisation (JCVI), recommended that the UK introduce a vaccination programme for gay men, to be delivered via sexual health clinics. The rationale behind the recommendation is that heterosexual men will be protected from HPV infection because most women will have been immunised, but that men who have sex with men will miss out on “herd immunity”.

However, campaigners and some experts say this reasoning is flawed, as many gay men will have been sexually active before their first visit to a sexual health clinic, and would most likely have already contracted or transmitted the virus.

The JCVI is due to consider the cost-effectiveness of vaccination for boys but campaigners do not anticipate any decision until 2017.

However, the NHS in London is currently planning what would be the first pilot of routine HPV vaccination for boys, with a likely start date of February 2016. The “field test” will work across four sites to establish whether school-age young males would “embrace the uptake of HPV vaccination as part of a community programme”, NHS England’s London office said.

Rolling out the vaccine to boys would require a public-information campaign because it has previously been presented to parents and children as a girls-only jab to prevent cervical cancer.

Scientists say changes in sexual behaviour – with more couples having oral and anal sex – may be the cause of increased cases of anal and throat cancers in both men and women in recent decades.

Margaret Stanley, emeritus professor at the University of Cambridge and a leading expert on HPV, said that cases could continue to rise. “It’s very much under-thirties [having more anal and oral sex] so you can predict there will be a rise in both those cancers. It’s a time bomb,” she said. “Wider exposure to different sexual practices – in other words porn on the internet – is also changing sexual behaviour in teenagers.”

HPV is also the cause of genital warts, the second-most common sexually transmitted infection in the UK. There are nearly 90,000 cases annually, costing the NHS around £55m. Campaigners hope that figure will be taken into account when the JCVI weighs up the cost-effectiveness of a vaccination programme.

Despite safety concerns being raised about the vaccine’s alleged side effects in some parts of the world, including Japan, no causal links have been established between the vaccine and reported long-term health problems. It is approved by the World Health Organisation, as well as European and UK vaccine-safety authorities. Professor zur Hausen added that it was “one of the safest vaccines we have”.

8-Injection-GetRolling out the vaccine to boys would require a public-information campaign because it has previously been presented to parents and children as a girls-only jab to prevent cervical cancer (Getty)

 

A Department of Health spokesperson said: “The HPV-prevention programme is key in helping us prevent cervical cancer. We have successfully given more than a million doses in the UK since 2008.

“Our independent vaccination experts are assessing whether it should be extended to prevent cancers in adolescent boys, men who have sex with men, or both.”

Time for an update?

Parents are currently advised and asked for consent for their daughters to have the HPV vaccination through a form and information leaflet sent out via schools.

The vaccine’s preventative effects against cervical cancer and the protection it offers against genital warts are explained. The protection against other cancers is not mentioned.

Parents and children are told that the vaccine, which is now given in just two doses instead of three, protects against 70 per cent of cervical cancers and that girls will still require cervical screening tests when they are older. Newer versions of the vaccine may protect against more cases in the future.

Parents are told that the vaccine may cause “soreness, swelling and redness in the arm” that will wear off in a couple of days. The leaflet states that “more serious side effects are extremely rare” and reassures parents that it meets European and UK safety standards. However, parents have the option to deny permission for their daughters to have the jab – and are told it would be “helpful” if they gave reasons for refusal.

The leaflet is directly targeted at girls and their parents and focuses on cervical cancer. If the Government were to extend the HPV-vaccination programme to boys, they would have to reconsider how the vaccine was presented to parents and children. The current programme has had impressive uptake, possibly in part because the key reason for taking the vaccine – to prevent cervical cancer – is straightforward and well understood. It may be that in a new HPV vaccination programme, the jab could be presented more broadly as protection against “a range of cancers”.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

Single Dose of HPV-16/18 Vaccine Looks to Be Sufficient

Source: www.medscape.com
Author: Jenni Laidman
 

A single dose of a vaccine against human papillomavirus (HPV) may prevent cervical cancer as effectively as the standard three-dose regimen, researchers concluded after analyzing the combined results of two large vaccine trials. The HPV vaccine in these studies was Cervarix (GlaxoSmithKline), which is effective against HPV strains 16/18.

If randomized controlled trials ultimately support the result of this post hoc analysis, it could broaden protection against cervical cancer in areas of the world where vaccination programs are hardest to administer and where cervical cancer is disproportionately burdensome, the study authors say.

“Even if you ignore the expense, the feasibility of implementing and getting back to individuals for a second and third dose is quite challenging, especially in places where there is no infrastructure,” coauthor Cosette Wheeler, PhD, Regents Professor, Pathology and Obstetrics and Gynecology, University of New Mexico Health Sciences Center in Albuquerque, told Medscape Medical News.

The studies are published online June 10 in the Lancet Oncology.

The possibility of a single-dose HPV vaccine is “a huge public health win,” coauthor Aimée R. Kreimer, PhD, Investigator, Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, Maryland, told Medscape Medical News. “Even if one dose protects only against HPV types included in the vaccine formulation, if we vaccinated most girls, we would have the chance to reduce cervical cancer by around 75%.”

That’s the exciting part, Dr Wheeler added. “If we’re able to achieve success with one dose, or frankly even with two doses, that makes the possibility for worldwide prevention much greater.”

HPV type 16 is the leading cause of cervical cancer, responsible for about 50% of all cases, and HPV 18 is the second-largest cause, at 20%.The authors note that this research was carried out with Cervarix, and it is unclear whether the results would also apply to the other HPV vaccine that is available, Gardasil (Merck & Co.), which is active against several more HPV strains and is the product that is commonly used in the United States. Whether results of this trial have any bearing on Gardasil will depend on what’s driving the strong immune response to Cervarix, the authors suggest. Cervarix carries a proprietary adjuvant, which may be responsible for the immune response.

Surprise Over Efficacy Findings

The idea of the current post hoc analysis arose from results in the large randomized controlled Costa Rica Vaccine Trial, in which about 20% of participants received fewer than three doses of HPV-16/18 vaccine. “We were surprised to observe that efficacy was the same regardless of the number of doses received,” Dr Kreimer told Medscape Medical News.

That led to the post hoc analysis of the immunization results from the Costa Rica Vaccine Trial combined with results from the only other large phase 3, double-blind, randomized trial of HPV-16/18, for a total of more than 14,000 participants, ages 15 to 25 years, including about 7000 control subjects. The second trial, called PATRICIA (Papilloma Trial Against Cancer in Young Adults), took place in 14 countries. The analysis found that 4 years after vaccination, women who received the required three vaccine doses and women who received fewer than three doses — usually due to pregnancy or a colposcopy referral — were equally protected against HPV-16/18. Further, the analysis showed a potential benefit of cross-protection against closely related HPV strains 31/35/45 among women whose two doses were 6 months apart — a benefit previously seen only with three doses.

Four-year vaccine efficacy against HPV-16/18 in the combined analysis was 77% for the 13,296 (6634 case, 6662 control) women in the three-dose group, 76% for the 549 (273 case, 276 control) women in the two-dose group, and 85.7% for the 238 (138 case, 100 control) women in the single-dose group. Efficacy against the closely related HPV-31/33/35 was 59.7% for three doses, 37.7% for two doses, and 36.6% for one dose. When data for the two doses were analyzed according to dosing regimen, the cross-protective efficacy was 10.1% for those who received their second dose 1 month after the first and 68.1% for those who received the second dose at 6 months.

Antibody concentrations for two doses given 6 months apart were very close to concentrations for three doses, the research showed. One-dose vaccination titers at 6 to 48 months were lower than those for two or three doses, “but the titers were stable and several times higher than those identified for natural immunity,” the researchers write. “We can now infer that these lower, vaccine-induced antibody titers provide as strong HPV prevention as the titers from two or three doses, at least in the short term.”

Just how long these vaccines will provide protection still needs to be determined. “We know with three doses we can see the protection going out toward 10 years, and we hope that maybe the protection is lifelong,” commented Dr Wheeler. “That does not mean that we know we will never need a booster. And that doesn’t mean if we give less than three doses that we know about the longevity or durability of that protection. So that’s another piece of the puzzle.”

Although these results cannot be applied to Gardasil, Dr Wheeler notes that studies looking at Gardisil antibody titers after two doses look promising.

In an accompanying comment, Julia M.L. Brotherton, Medical Director, National HPV Vaccination Program Register, VCS Registries, East Melbourne, Victoria, Australia, commented: “These data suggest that one dose of bivalent HPV vaccine might be adequate to protect against HPV-16 and HPV-18 persistent infections and, therefore, probably disease. HPV-16 and HPV-18 cause more than 70% of cervical cancers and the vast majority of HPV-related cancers at other anatomic sites. If this finding is confirmed, it opens up a great opportunity to extend the reach of protection using HPV vaccines to more people than we would have previously thought possible.”

Four authors of the study are GSK employees and own shares and stock options in the company. Other researchers had financial or advisory relationships GSK, Roche Molecular Systems, Merck, and Sanofi Pasteur MSD. Dr Brotherton notes that she has been an investigator for investigator-initiated HPV epidemiology research grants partially funded by bioCSL/Merck, but this did not involve financial compensation.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

The Beginning of the End: Vaccine Prevention of HPV-Driven Cancers

Source: JNCI – Journal of the National Cancer Institute

Anna R. Giuliano, Aimée R. Kreimer and Silvia de Sanjose
+ Author Affiliations

Affiliations of authors: Center for Infection Research in Cancer, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (ARG); Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (ARK); Cancer Epidemiology Research Programme, Catalan Institute of Oncology, IDIBELL, Spain (SdS); CIBER Epidemiologia y Salut Pública, Barcelona, Spain (SdS). Correspondence to: Anna R. Giuliano, PhD, Professor and Director, Center for Infection Research in Cancer, H. Lee Moffitt Cancer Center and Research Institute, MRC-CAN CONT, 12902 Magnolia Drive, Tampa, FL 33612 (e-mail: anna.giuliano@moffitt.org).
In this issue of the Journal, Saraiya and coauthors present an important analysis of human papillomavirus (HPV) detection in tumors retrieved from select US sites prior to HPV vaccine implementation (2006) (1). Not only are these data necessary to evaluate future vaccine effectiveness in reducing cancers caused by HPV infection, but they will also aid in the growing assessment of the worldwide burden of tumors attributable to HPV infection. These data raise the question: How many cases of cancer can be prevented by HPV vaccination in the United States?

Twenty years ago, in 1995, the World Health Organization recognized for the first time that HPV 16 is the cause of cervical cancer. In 2005, 10 years after this report, there was sufficient accumulated evidence to state that HPV 16 is also the cause of multiple cancers in men and women, and that HPV 16 is only one of 13–15 HPV types deemed “high-risk” types that cause cervical cancer (2,3). Growing evidence that HPV causes cancers, combined with the technology to develop efficacious vaccines against DNA viruses (4), simultaneously led to vaccine development. This was followed by demonstration of vaccine efficacy in women and men (5–8) and, ultimately, licensure of multiple vaccines that protect against HPV infection acquisition and prevention of the lesions these viruses cause (9–11). The recent licensure in the United States of Gardasil 9 presents an opportunity to further expand vaccine protection to prevent 90% of all cervical cancers worldwide (12,13).

While there has been tremendous progress in the prevention of cervical cancer through screening of adult women in high-resource countries and, recently, prevention of cervical precancer with vaccination (14), less progress has been made in the prevention of HPV-related cancers in men, cancers for which screening interventions are not routinely available. Despite clear evidence that HPV causes cancer at the oropharynx, that HPV-related oropharyngeal cancers (OPC) disproportionately affect men, and that OPC incidence is increasing in the United States, there have been no trials conducted to assess the efficacy of HPV vaccines to prevent these cancers. There is preliminary evidence of prophylactic HPV vaccine efficacy against prevalent oral HPV16/18 infections in women (15); however, it remains unknown what proportion of HPV-related OPC can be prevented with broad dissemination of HPV vaccines to males. Moreover, it remains unclear what proportion of OPC that have HPV DNA present are truly attributable to HPV.

Using HPV DNA-based detection to ascribe causality to tumors at different anatomic sites requires caution. There is strong evidence that HPV infection causes all cervical cancers and that DNA detection correlates well with markers of viral activity; thus, the use of DNA detection alone may be well justified at the cervix. However, for noncervical sites, particularly in the head and neck, HPV DNA-based detection methods overestimate the HPV attributable proportion. Identification of viral DNA in the tumor can occur if there is simply a transitory infection (not causal), as well as in cases where HPV is causally involved in the development of the tumor (transcriptionally active). Thus, identification of viral transcripts of the E6/E7 oncogenes by detection of the related mRNA and downstream markers, such as p16INK4a expression, is an approach utilized to ascertain whether HPV is causally involved in the development of the tumor. As an example, a recent meta-analysis of the attributable fraction of HPV in head and neck squamous cell carcinomas showed that HPV DNA was detected in 46% of OPC, 22% of laryngeal cancers, and 24% of oral cavity cancers. When E6/E7 mRNA and p16INK4a status were assessed in these same tumors, the proportion caused by HPV infection was similar for OPC (40%) but overestimated for laryngeal (9%) and oral cavity cancer (16%). Thus, in the current analysis (1), in which 70% of OPC, 21% of laryngeal cancers, and 32% of oral cavity cancers were HPV DNA–positive, it is possible that the HPV attributable fractions for oral cavity and laryngeal cancers were overestimated by two- to three-fold, respectively. Given the documented increases in the proportion of OPC tumors attributable to HPV over the past several decades, the absolute number of cases due to HPV should not be viewed as static; future estimates of the HPV-related OPC burden may be affected by changes in the underlying causes of these cancers, including smoking prevalence and HPV, especially as vaccination dissemination increases. Similar data on the importance of using measures of viral activity to determine HPV causality for noncervical anogenital tumors (penile, vulvar, vaginal, anal) are currently unavailable but will be critical in determining whether HPV DNA detection is sufficient to determine causality (as at the cervix) or whether markers of viral activity should also be utilized (as at the larynx and oral cavity).

Most cancer registries do not have access to molecular data to classify HPV infection status and therefore rely on anatomic site and histology to estimate HPV-related cancer incidence and case counts. In a best-case scenario, such as reported by Saraiya et al., registries have access to discarded samples that enable molecular analysis of tumors. For the purposes of monitoring HPV vaccine impact, these data allow surveillance of HPV-related tumor burden reduction in the post-HPV vaccination era. However, studies aiming to determine the true attributable proportion of HPV in cancers outside the cervix should assess causality with laboratory measures that capture viral activity.

The proportion of HPV-driven cancers that can be prevented with HPV vaccination differs by world region. The United States, like other high-resource countries with organized cervical cancer screening programs, has a low invasive cervical cancer rate but higher rates of noncervical cancers, particularly OPC in men. In contrast, in countries that have not yet benefited from cervical cancer screening programs or tobacco control policies, cervical cancer incidence is higher and HPV-related OPC incidence lower. In the last decade, OPC incidence increased in many economically developed countries as smoking prevalence decreased (16,17). Data reported in this issue indicate that approximately 60% to 70% of OPCs are caused by HPV infection in the United States (1), contrasting with data reported from less economically developed regions where less than 10% of tumors are HPV-positive (18–20). In a comprehensive review of the global burden of infection-associated cancers, de Martel et al. estimated that HPV infection accounts for 38% to 56% of OPC in Australia, Japan, North America, and Northern and Western Europe, compared with only 13% to 17% of OPC in other parts of the world (21). The proportion of OPC attributed to HPV may be even lower in certain African countries (19).

Regardless of how precisely we define the total number of cases due to HPV, vaccination against HPV has the potential to prevent multiple cancers in men and women, cancers for which we have no evidence-based prevention modalities, except in the case of cervical cancer. The data presented by Saraiya and coauthors estimate the number of cancers in the United States we can expect to prevent in the era of HPV vaccination. However, until we reach the national goal of 80% of men and women fully vaccinated against HPV (22), the prevention of multiple cancers with a relatively simple intervention will remain a dream. Providers are the key to implementing the national vaccine recommendations, ensuring this dream becomes a reality. Strong messages from providers to vaccinate age-eligible men and women can move the United States from among the lowest rates of HPV vaccination to the highest, with reductions in the national cancer burden to follow sooner rather than later.