Fact check: Michael Douglas on HPV and throat cancer

Source: www.huffingtonpost.com
Author: Meredith Melnick

A Michael Douglas interview in The Guardian caused waves when the publication reported that the “Behind the Candelabra” star revealed HPV, the human papilloma virus, to be the cause of his stage-4 throat cancer diagnosis in 2010.

“Without wanting to get too specific, this particular cancer is caused by HPV, which actually comes about from cunnilingus,” Douglas allegedly told The Guardian.

Douglas, through his publicist, has said that the statement was misinterpreted: He wasn’t saying that his cancer was caused by the sexually transmitted disease — merely that many cancers like his are HPV-positive. As The Daily Beast points out, there is scant research evidence to directly link the act of cunnilingus with HPV infection. But regardless of the details of his own cancer, the actor is right about one thing: A growing majority of oral cancer cases are caused by HPV.

While most strains of HPV clear up on their own, the sexually transmitted disease is responsible for an array of cancers. As Douglas describes, it’s true that oral sex is an avenue through which a person can contract HPV and especially the strains, HPV-18 and HPV-16, the latter of which is responsible for half of oral cancer cases, according to the National Cancer Institute. HPV-16, HPV-18 and some less-common strains can also cause cancers of the cervix, vagina, vulva, anus and penis.

Douglas’ experience follows trends in cancer diagnosis, according to a January report from the American Cancer Society, which found a rise in oral cancer caused by HPV in both women and men. As the report said, as of 2004, 72 percent of oral cancer tumors were HPV-positive — up from 16 percent of tumors in data collected between 1984 and 1989.

Previously, excessive drinking and tobacco use were the most common causes of the throat cancer Douglas developed, but HPV has replaced tobacco as the leading cause of throat cancers. HPV’s rise as the leading cause of oral cancer is not just the result of growing rates of the virus — it is also explained by drops in smoking, thanks to public health campaigns that describe the dangers of cigarette use.

HPV-16 and 18 are targeted by the vaccine Cervarix and are two of the four strains targeted by Gardasil, the other of the two approved vaccines against HPV. Gardasil is currently recommended for boys between the ages of 13 and 21 and both Cervarix and Gardasil are recommended for girls, aged 13 to 26, according to the Centers for Disease Control and Prevention. HPV-6 and HPV-11, both of which the Gardasil vaccine immunizes against, cause about 90 percent of genital warts cases.

Despite the growing rates of oral cancer, cases like Douglas’ are still relatively rare, with about 7,100 new cases each year, reported USA Today. But that doesn’t mean oral HPV infection is rare: According to a 2012 study of Americans, aged 14 to 69, about 10 percent of men and 3.6 percent of women currently have an oral HPV infection.

According to the CDC, there is no screening test to determine overall HPV status. While women are screened for HPV-associated cervical cancer via a Pap-smear test, other HPV-associated cancers don’t have a specific screening test. Despite the fact that there are no uniform screening techniques for oral cancer, the prognosis for the disease is good, with an 80 to 90 percent survival rate, according to The Oral Cancer Foundation.

Dose of reality: HPV is epidemic, which is odd since it is largely preventable

Source: www.sciencenews.org
Author: Nathan Seppa

There are two vaccines that guard against human papilloma­virus, and they are in rare company among medical inventions — the vaccines prevent cancer. Only the hepatitis B vaccine can make the same claim. Cancer-causing HPV can trigger abnormal cell growth on the cervix, and cervical cancer still kills up to 4,000 U.S. women each year. The virus is also implicated in cancers occurring in the anus and the throat. All told, according to a 2011 study, 29 percent of sexually active U.S. girls and women carry a potentially cancer-causing HPV infection.

Preteen and adolescent girls and boys are priority groups for vaccines that prevent human papillomavirus infection.© Jessica Rinaldi/Reuters/Corbis

Preteen and adolescent girls and boys are priority groups for vaccines that prevent human papillomavirus infection.
© Jessica Rinaldi/Reuters/Corbis

Back in 2006 and 2009, when the HPV vaccines Gardasil and Cervarix came onto the market, health officials dreamed of halting the spread of HPV, which is sexually transmitted, in a single generation. Scientists call such blanket coverage herd immunity — in which a pathogen gets vaccinated into oblivion, becoming so rare that even unvaccinated people are protected.

With such heady potential, Gardasil, developed by Merck, and Cervarix, created by GlaxoSmithKline, should be an easy sell. They rev up a potent immunity against HPV 16 and 18, the two types of the virus that account for most cases of cervical cancer. Gardasil also prevents most genital warts. The immunity the vaccines provide is many-fold better than the weak protection engendered by a run-in with the virus itself, and since approval, both vaccines have proven safe. A study of nearly 190,000 girls and women, published in 2012 in Archives of Pediatric and Adolescent Medicine, found that the shots’ most common side effects were mild skin infections and fainting.

But the hope for herd immunity against HPV anytime soon is fading fast in most of the West. By 2011, only 53 percent of U.S. teenage girls from 13 to 17, a target group for the vaccines, had received them.

“It’s a disaster,” says Andreas Kaufmann of Charité University Medicine Berlin, who sees the problem from the perspective of a biologist. “HPV is strictly species-specific. It only occurs in humans.”

WHY WAIT?Many U.S. mothers are reluctant to have preteen daughters vaccinated, even though that’s when protection is most likely to prevent a future HPV infection.Source: J. Kahn et al/Pediatrics 2009

Many U.S. mothers are reluctant to have preteen daughters vaccinated, even though that’s when protection is most likely to prevent a future HPV infection.
Source: J. Kahn et al/Pediatrics 2009

That means with mass vaccination, the virus would have no safe harbor in nature. “Theoretically, we could eradicate these HPV types, like we did smallpox,” he says. “We could end it.”

What’s the problem?
Most childhood immunizations are doled out in infancy. Although preteens and older kids routinely get shots or boosters for whooping cough, measles and meningitis, the HPV vaccines stand apart from those other shots like an unpopular kid.

For one thing, parents are uneasy about vaccinating a preteen against a virus associated with sexual activity. Researchers have found that some parents believe vaccination might lead to greater promiscuity. And a public scare about vaccines in general — including a false report linking the measles vaccine to autism — has contributed to the confusion. Not only that, but the vaccine is delivered in a three-shot regimen. Even among girls who get vaccinated, completing the course isn’t a certainty. Many U.S. preteen and teenage girls who start the course fail to get all three shots, and thus are less apt to be protected.

In the United States, responsibility for tracking kids’ HPV shots often falls to pediatricians, since the vaccine isn’t administered in schools. But pediatricians are notoriously overworked and — relative to many other physicians — underpaid. Doctors often need to cover vaccine costs up front to have them ready for patients, says Kevin Ault, a gynecologist at Emory University in Atlanta. Pediatricians also have to remind a patient to return for subsequent shots and often find themselves on the front line in contending with doubtful parents, says Noel Brewer, a health psychologist at the University of North Carolina in Chapel Hill. Instead of mass vaccinations in schools, the HPV vaccines depend on this hit-or-miss distribution system managed by individual doctors who, even if they advocate vaccination, may not want to cross parents. The result is often family indecision, procrastination and outright rejection.


FALLING BEHINDHealth guidelines recommend the three-shot HPV vaccine for the best protection against cancer. But recipients don’t always complete the regimen. Compliance is worse in some states than in others.Source: A. Jemal et al/JNCI 2013; Image: Geoatlas/Graphi-Ogre, adapted by E. Feliciano

Health guidelines recommend the three-shot HPV vaccine for the best protection against cancer. But recipients don’t always complete the regimen. Compliance is worse in some states than in others.
Source: A. Jemal et al/JNCI 2013; Image: Geoatlas/Graphi-Ogre, adapted by E. Feliciano

Then there’s the behavior of the virus itself. The vaccines don’t work in people who have active HPV infections, and it’s difficult to know who those people are. The cancer-causing HPV types are stealthy, giving rise to phantom infections with no symptoms and an iffy risk of cancer far off in the future. These characteristics make the risks posed by HPV hard to grasp, says Christina Dorell, a physician at the Centers for Disease Control and Prevention. “With polio, people were getting sick and going to the hospital,” she says. “When the image of illness is removed from a group, you may have a little less sense of urgency coming from parents.”

Girls might see it differently, studies show. Doctors’ opinions matter to them. Those who receive a recommendation from a doctor are 2.6 times more likely to get vaccinated than girls getting no counsel, researchers reported in Pediatrics in 2011. Also, “there is no evidence of increased sexual-risk behavior, such as decreased condom use or earlier intercourse,” says Gregory Zimet, a clinical psychologist at the Indiana University School of Medicine in Indianapolis. Other work has found no increase in sexually transmitted diseases after HPV vaccination. “The whole [promiscuity] argument is false, actually,” Zimet says.

More likely, many parents are in denial about their teens’ sexuality, says Kaufmann: “Parents don’t believe that a 15-year-old daughter may already be sexually active.” But a 2010 U.S. survey found that at least 12 percent of 14- and 15-year-old girls had engaged in oral sex or intercourse or both.

One way to skirt the problem might be to vaccinate earlier. Health psychologist Jo Waller of University College London says focus groups show that parents like the idea of vaccinating girls as young as age 8 or 9, since that means skipping the chat about how the vaccine prevents sexual transmission of HPV. “They wouldn’t have to open that can of worms,” she says. Some countries do begin vaccinating at age 9, and several trials are under way testing the effectiveness of the shots at that age.

The fact of the matter is that the science underlying the HPV link to cancer is unassailable. German scientist Harald zur Hausen discovered the connection in the 1980s and was awarded a 2008 Nobel Prize for his efforts (SN: 10/25/08, p. 10). While Pap smears have averted most deaths from cervical cancer in the United States, the malignancy remains a leading cause of women’s cancer worldwide. Three shots of Gardasil or Cervarix protect against HPV types responsible for 70 percent of cervical cancers.

The other half of the equation
While cervical cancer is the most common malignancy prevented by the vaccines, in the United States nearly two-fifths of HPV-related cancers occur in men. That’s because HPV can cause cancers in the mouth or throat areas, and those strike both sexes. HPV is implicated in roughly 60 percent of oral cancers that affect the back of the tongue, throat and tonsils. Although many of these malignancies arise from alcohol and tobacco consumption, those types of cancers have declined in the United States in recent years even as overall oral cancer rates have stayed the same. HPV-related oral cancers account for the rise, particularly in men. In Denmark, the past decade has brought a shift in tonsil cancers, from 43 percent containing HPV to 75 percent.

WORLD VIEWHPV vaccines can prevent cervical cancers. Although roughly 40 countries worldwide now have HPV vaccination in their national health guidelines, few low-income countries — where cervical cancer remains a major problem — are in this group. However, pilot programs in some poorer nations indicate that the vaccine is well accepted, particularly when delivered at schools.Source: M. Forouzanfar et al/Lancet 2011, adapted by E. Feliciano

HPV vaccines can prevent cervical cancers. Although roughly 40 countries worldwide now have HPV vaccination in their national health guidelines, few low-income countries — where cervical cancer remains a major problem — are in this group. However, pilot programs in some poorer nations indicate that the vaccine is well accepted, particularly when delivered at schools.
Source: M. Forouzanfar et al/Lancet 2011, adapted by E. Feliciano

Scientists established a link between oral cancer and HPV more than a decade ago when studies revealed HPV 16 lurking in many oral tumors. In 2007, researchers at Johns Hopkins University found that oral cancer patients were three times as likely as people without the cancer to have had six or more partners on whom they had performed oral sex. But there’s much still unknown about the dynamics of oral HPV transmission, says epidemiologist Marc Brisson of Laval University in Quebec. “Kissing may be involved.” He and others thinks that changing sexual practices may be behind the rise in oral cancers.

HPV vaccination is now recommended for boys in the United States (SN Online: 10/26/11). But because approval came later than it did for girls, only about 8 percent of boys ages 13 to 17, the initial target group, got at least one shot in 2011. As with girls, 11- to 12-year-old boys are the main vaccination target. But teenagers and young adults of both sexes can get the shots as part of a catch-up effort.

The HPV vaccines are given to prevent genital or anal HPV infections. Vaccine companies can’t make any claims regarding oral cancer because the vaccines haven’t been tested to prevent it. But the evidence is strongly suggestive.

“It’s time to start vaccinating boys,” says Margaret Stanley, a pathologist at the University of Cambridge in England. Boys and young men in Britain are not yet getting the shots, but Stanley and others are pushing for it. “It will protect 50 percent of the population, and not doing so would be truly discriminatory because that would include gay men, who are very much at risk of anal cancer,” she says. “And if you vaccinate boys, you start to get herd immunity.”

A shot at the herd
The slow launch of HPV shots in many countries is reminiscent of an earlier campaign that also could have stopped a sexually transmitted virus and the cancer it causes. “With the hepatitis B vaccine, we essentially lost a generation,” says Basil Donovan, a sexual health physician at the Kirby Institute and the University of New South Wales in Sydney. Slow implementation since the hepatitis B vaccine became available three decades ago has left the 350 million hepatitis B carriers worldwide at an increased risk of liver cancer.

RISK ASSESSMENTMore than a dozen types of HPV can trigger abnormal tissue growth and malignancy in humans. The cancer burden affects women and men differently, as this chart of U.S. cases demonstrates.Source: A. Jemal et al/JNCI 2013, adapted by E. Feliciano

More than a dozen types of HPV can trigger abnormal tissue growth and malignancy in humans. The cancer burden affects women and men differently, as this chart of U.S. cases demonstrates.
Source: A. Jemal et al/JNCI 2013, adapted by E. Feliciano

Similarly, delayed HPV vaccination chalks up a daily cost as more teens become sexually active without protection. About 6 million new genital HPV infections occur each year in the United States, mostly in teens and young adults. Oral HPV infections go uncounted. Canada is faring better, but a study there found that while parents permitted their daughters to get hepatitis B shots in school at an 88 percent rate, only 65 percent consented to HPV vaccination. Germany has lagged behind some other European countries because shortly after the HPV vaccines were introduced, vaccine opponents raised questions about side effects of the shots. “Doctors stopped recommending it,” Kaufmann says.

Life is different in Australia. There, public health officials have now documented mass HPV vaccination and the first glimmers of herd immunity. Australian authorities have left little to chance, vaccinating preteen and teenage girls in schools since 2007. They mainly use Gardasil, which prevents genital warts, and such warts are vanishing in young women coming into city clinics. This year Australia began vaccinating boys, too, but herd immunity in them started showing up even before the first shot was fired into a boy’s arm. It seems that protecting girls means protecting boys.

Australia’s school-based program to vaccinate girls against HPV, mainly with Gardasil, is showing benefits for both sexes. Public health officials examining urban clinic records have documented a steady decline in genital warts. The findings hint at herd immunity.

TRENDING DOWNWARDAustralia’s school-based program to vaccinate girls against HPV, mainly with Gardasil, is showing benefits for both sexes. Public health officials examining urban clinic records have documented a steady decline in genital warts. The findings hint at herd immunity.Source: H. Ali et al/International Union Against STI World Congress in Melbourne 2012

Australia’s school-based program to vaccinate girls against HPV, mainly with Gardasil, is showing benefits for both sexes. Public health officials examining urban clinic records have documented a steady decline in genital warts. The findings hint at herd immunity.
Source: H. Ali et al/International Union Against STI World Congress in Melbourne 2012

Australia’s school-based vaccination program, which offers Gardasil free of charge for students, has set the pace for other nations. Between 2007 and 2009, 83 percent of preteen and teenage girls designated for vaccination had gotten at least one shot and 70 percent had received all three. More than half of young adult women got at least one shot, too.

Within two years of the program’s start, the rate of genital warts among girls and women was dropping every quarter at clinics monitored by scientists, Donovan says. Among women under age 21 examined at a eight clinics in Australia in 2011, less than 1 percent had genital warts, compared with more than 8 percent during the pre-vaccination years. Also in 2011, of 235 women who had been vaccinated against HPV, none had any warts, Donovan says. “Warts were a fairly obvious thing to monitor,” he says, since they can appear within months of infection. “In contrast, for cancer it’s measured in decades.”

Updated Australian data were released in late 2012 at conferences in Melbourne and San Juan, Puerto Rico. What really shocked attendees was the finding that genital warts in young men also dropped — from a range of 7 to 14 percent in pre-vaccination years to about 2 percent in 2011 — even though the widespread vaccination of boys hadn’t yet started in Australia.

The findings have changed how some people view HPV vaccination campaigns, Brewer says. “The data in Australia are just jaw-dropping.” Danish researchers recently reported substantial declines in warts as well.

Waller says the findings in heterosexual Australian men offer proof that there is herd immunity developing from having vaccinated women in Australia. “That leaves men who have sex with men as the main unprotected group,” she says.

The United States has special problems with school-based vaccination programs because there is no national health insurance that will cover the cost of the vaccine, as is the case in Britain, Canada and Australia. Still, a demonstration project in Denver is investigating a school-based program, says Lauri Markowitz, a medical epidemiologist at the CDC. While states can make vaccinations mandatory for school entry, mandates for HPV are rare, with only schools in Virginia and the District of Columbia requiring the shots.

In the long run, herd immunity remains the goal, and it’s not exotic. Anyone with children sees herd immunity in action. Routine childhood vaccines given to babies nowadays largely maintain herd immunity against scourges that beset previous generations. “The risk is near zero for an individual ever getting polio again,” Zimet says. “We continue to use the Salk vaccine to maintain herd immunity.”

The outlook for HPV may improve in coming years. Markowitz reported at the Puerto Rico meeting that among U.S. teenage girls, the rate of HPV infections of the types covered by the vaccines fell from 11.5 percent before vaccination introduction to 5.1 percent in the years after it, based on a nationwide database. And California public health authorities reported in 2012 that medical records show a substantial decline in genital wart diagnoses in girls in the post-vaccination years and a modest drop in boys.

Also, Merck is testing a new vaccine that covers the four HPV types in Gardasil as well as five others that can cause cancer. Math models suggest it could have a big impact on the HPV infection rate. “This seems like a great step forward,” says Zimet, who expects a nine-type vaccine to get cleared within a year or two.

Such a vaccine would help turn the tide, Stanley says. “You really want to prevent 90 percent of cervical cancers,” she says, “and that’s what it should do. Eventually, you wouldn’t need to screen for them [with a Pap smear]. You’d be looking for a rare disease. We ought to have no cervical cancer in 20 years.”

Other help might come financially. The Affordable Care Act — “Obamacare” — will eventually require insurance plans to cover all recommended vaccines, including HPV.

“The solution to the problem,” says Brewer, “is to improve the public health system we have. It may not rest solely on getting parents to act.” He suggests delivering HPV vaccines in schools and at pharmacies, like flu shots, and getting doctors to implement a system to recommend them routinely. “One or all of those would work,” he says.

Vaccinating against cancer
There are over a hundred types of human papillomavirus, says Robert Burk, a medical geneticist at the Albert Einstein College of Medicine in New York. But only about a dozen cause the vast majority of HPV-related cancers — and they take years or decades to do it. Still, those few viruses’ stealth makes them dangerous. Over millennia the viruses have perfected the art of colonizing humans and create very little stir when they do.

“In most of us the immune system recognizes the virus and deals with it,” says Margaret Stanley, a pathologist at the University of Cambridge in England. But these viruses can evade people’s immune reactions better than most. In some unlucky few, HPV triggers genetic mutations in the cells it infects, leading to abnormal cell growth and even to cancer. “A fraction of immune systems cannot handle these viruses well,” Stanley says. “We don’t know why.”

The Gardasil and Cervarix vaccines alert the immune system to the two most-studied cancer-causing HPV types, HPV 16 and 18. Together, these two viruses are thought to cause some 70 percent of cervical cancer. The vaccines against them appear effective, with evidence suggesting that even two doses may provide protection.

Research has now targeted several other cancer-causing members of the HPV family, and work is under way to test a nine-type vaccine that would add protection against HPV 31, 33, 45, 52 and 58. Gardasil and Cervarix may induce the immune system to develop partial cross-protection against these other HPV types. However, such cross-protection is not as strong as direct immunity.

Basil Donovan of the University of New South Wales in Sydney estimates that by the end of a young woman’s first sexual partnership, she has a 30 percent chance of having acquired an HPV infection. A 2011 study found that 43 percent of sexually active U.S. girls and women up to age 59 were carrying some type of HPV infection. Among U.S. men, the rate was about 50 percent for an HPV infection. In Germany and Denmark, the infection rate is roughly 35 to 40 percent among young women, says Andreas Kaufmann of Charité University Medicine Berlin.

“The vaccine has no effect on existing infections,” Burk cautions. But women who have been vaccinated before being diagnosed with an abnormal cell growth on the cervix — and treated to have the potentially precancerous growth removed — may benefit from that prior vaccination, researchers reported in BMJ in 2012. Vaccinated women were about half as likely as their unvaccinated counterparts to be diagnosed with a repeat lesion. Whether it’s useful to vaccinate a woman after she has cleared a lesion with surgery remains an open question, says gynecologist Kevin Ault of Emory University. But if it does help, those women would be prime candidates for vaccination since they would certainly be members of the unlucky few.

– George Papanicolaou develops Pap smear

– Harald zur Hausen’s team isolates HPV in genital warts

– zur Hausen’s team isolates HPV in cervical cancer
– Early vaccine development

– HPV vaccines developed
– HPV linked to oral cancers
– HPV found in 99.7 percent of cervical cancers

– Clinical trials of HPV vaccines
– Gardasil recommended for girls and young women (2006)
– zur Hausen wins Nobel Prize (2008)
– Cervarix recommended for girls and young women (2009)

– HPV vaccines recommended for boys and young men (2011)

H. Bauer et al. evidence of human papillomavirus vaccine-effectiveness in reducing genital warts: An analysis of California public family planning administrative claims data, 2007-2010. American Journal of Public Health. In press, 2012. doi: 10.2105/AJPH.2011.300465

R. Bednarczyk et al. Sexual Activity-related outcomes after human papillomavirus vaccination of 11-to-12 year olds. Pediatrics. Volume 130, Number 5, November 2012, p. 1. doi/10.1542/peds.2012-1516.

J. Berkhof and J. Bogaards. Vaccination against human papillomavirus types 16 and 18: the impact on cervical cancer. Future Oncology. Volume 6, 2010, p. 1817.

B. Donovan et al. Quadrivalent human papillomavirus vaccination and trends in genital warts in Australia: analysis of national sentinel surveillance data. Lancet Infectious Diseases. Volume 11, 2011, p. 39. doi: 10.1016/S14733099(10)70225-5

C. Dorell et al. Human Papillomavirus Vaccination Series Initiation and Completion, 2008–2009. Pediatrics. Volume 128, Nov. 1, 2011, p. 830. doi: 10.1542/peds.2011-0950

C. Dorell et al. National and state vaccination coverage among adolescents aged 13-17 years – United Sates, 2011. Morbidity and Mortality Weekly Report. Volume 61, Aug. 31, 2012, p. 671.

G. D’Souza et al. Case–control study of human papillomavirus and oropharyngeal cancer. New England Journal of Medicine. Volume 356, May 10, 2007, p. 1944.

C. Fairley et al. Rapid decline in presentations of genital warts after the implementation of a national quadrivalent human papillomavirus vaccination programme for young women. Sexually Transmitted Infections. Volume 85, 2009, p. 499. doi: 10.1136/sti.2009.037788

A. Forster et al. Human papillomavirus vaccination and sexual behavior: Cross-sectional and longitudinal surveys conducted in England. Vaccine. Volume 30, July 13, 2012, p. 4939.

M. Forouzanfar et al. Breast and cervical cancer in 187 countries between 1980 and 2010: a systematic analysis. Lancet. Volume 378, October 22-28, 2011, p. 1461. doi.org/10.1016/S0140-6736(11)61351-2.

E. Garnaes. Oropharyngeal cancer and HPV in a large Danish cohort. 28th International Papillomavirus Conference – Puerto Rico, 2012.

M. Gillison et al. Prevalence of oral HPV infection in the United States, 2009-2010. Journal of the American Medical Association. Volume 307, Feb. 15, 2012, p. 693. doi:10.1001/jama.2012.101

S. Hariri et al. Prevalence of genital human papillomavirus among females in the United States, the National Health and Nutrition Examination Survey, 2003-2006. Journal of Infectious Diseases. Volume 204, Aug. 15, 2011, p. 566. doi: 10.1093/infdis/jir341

D. Herbenick et al. Sexual behaviors in the United States: Results from a national probability sample of men and women ages 14-94. Journal of Sexual Medicine. Volume 7, 2010, p. 255. doi: 10.1111/j.1743-6109.2010.02012.x

A. Jemal et al. Annual Report to the Nation on the Status of Cancer, 1975–2009, featuring the burden and trends in human papillomavirus (HPV)–associated cancers and HPV vaccination coverage levels. Journal of the National Cancer Institute. Volume 105, 2013, p. 175. doi: 10.1093/jnci/djs491. [Go to]

E. Joura et al. Effect of the human papillomavirus (HPV) quadrivalent vaccine in a subgroup of women with cervical and vulvar disease: retrospective pooled analysis of trial data. BMJ. Volume 344, online March 27, 2012, p. e1401. doi: 10.1136/bmj.e1401

J. Kahn et al. Mothers’ intention for their daughters and themselves to receive the human papillomavirus vaccine: A national study of nurses. Pediatrics. Volume 123, June 2009, p. 1439. doi: 10.1542/peds.2008-1536

N. Klein et al. Safety of quadrivalent human papillomavirus vaccine administered routinely to females. Archives of Pediatric and Adolescent Medicine. Volume 166, December 2012, p. 1140. doi:10.1001/archpediatrics.2012.1451

A. Kreimer et al. Proof-of-principle evaluation of the efficacy of fewer than three doses of a bivalent HPV16/18 Vaccine. Journal of the National Cancer Institute. Volume 103, Oct. 5, 2011, p. 1. doi: 10.1093/jnci/djr319. [Go to]

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April, 2013|Oral Cancer News|

Should You Get the HPV Vaccine?

You don’t have to be a virgin to be protected against cancer.

By |Posted Friday, Jan. 25, 2013, at 1:22 PM ET

Source: Slate

A doctor gives a 13-year-old girl an HPV vaccination

A doctor gives a 13-year-old girl an HPV vaccination
Photo by Joe Raedle/Getty Images.

The human papillomavirus has the dubious distinction of being the sexually transmitted disease you are most likely to get. It’s also the leading cause of cervical cancer. January has, somewhat arbitrarily, been dubbed Cervical Health Awareness Month (also National Hobby Month and Hot Tea Month, the last at least for good reason). While cervical cancer is the disease most commonly associated with HPV, a recent report from the American Cancer Society emphasizes that HPV’s threat is not gender-specific or organ-specific. While cervical cancer cases are in decline (as are general cancer rates), cancers linked to HPV are on the rise.

The increasing prevalence of HPV-linked cancers should permanently alter our limited conception of the disease as chiefly a women’s issue. Oropharyngeal (which I’ll be vulgarizing as “oral”) and anal HPV-related cancers (which particularly afflict men who have sex with men) are becoming more common. Oral malignancies account for 37.3 percent of HPV-related cancers, edging out cervical cancer, which makes up 32.7 percent. For men, oral cancers make up 78.2 percent of total HPV-related cancer incidences, and they account for 11.6 percent of cases among women. The death rate for oral cancer is three times higher than that for cervical cancer. (About 40 percent of penile cancer cases are HPV-related, but rates of the disease have basically remained static.)

Historically, most oral cancer cases were caused by smoking and heavy drinking and tended to manifest later in life. But even though fewer Americans indulge in these vices today, more of them are engaging in oral sex. Oral cancer rates have risen and begun showing up in younger individuals who, sensibly, seem to prefer oral sex to cigarettes. As the Oral Cancer Foundation notes, HPV strain 16 “is conclusively implicated in the increasing incidence of young non-smoking oral cancer patients.” If the disease is detected, the survival rate for HPV-related oral cancer is higher than for the alcohol- and tobacco-correlated versions. But HPV-related cases are often harder to catch because the disease occurs deeper in the mouth (the base of the tongue is a common location), and the warning signs are not as obvious.

There are, of course, HPV vaccines, which the CDC describes as “very effective” and “very safe.” Merck released another study in October that found that Gardasil, the company’s vaccine, may cause fainting and brief skin irritation but “no link with more serious health problems was found.” The Gardasil vaccine defends against four HPV strains: 6 and 11, which cause 90 percent of genital warts; and 18 and 16, which are linked to cancer. It is FDA-approved and CDC-recommended for males and females. Cervarix defends against the same two cancer-causing strains and a few other lesser culprits. It is not licensed for men. Most insurance companies and public health programs will cover the cost of the HPV shots for those who fall between the FDA-licensed ages of 9 through 26 years old.

But while both vaccines successfully defend against various strains of HPV, only Gardasil has been specifically tested and proven to protect against vulvar, vaginal, and anal cancers as well as cervical cancer. The vaccines’ preventive abilities have not been proven for other cancers, which prevents the companies from advertising the vaccines’ usefulness against the most prevalent danger: HPV-related oral disease. As the CDC notes: “It is likely that this vaccine also protects men from other HPV-related cancers, like cancers of the penis and oropharynx (back of throat, including base of tongue and tonsils), but there are no vaccine studies that have evaluated these outcomes.” Last year the National Cancer Institute declined to fund proposed clinical trials on the efficacy of the vaccines for oral cancer, possibly due to budgetary constraints. (NCI officials were not able to respond before publication.)

“The very low rate at which boys are vaccinated is a result of the inability of the manufacturers and doctors to speak openly and with factual evidence about oral cancer in a context that parents will understand,” says Brian Hill, president of the Oral Cancer Foundation, who was present at the National Institute of Health meeting where the aid was requested. He says more data and publicity for the vaccines could improve the vaccination rate in boys, which in 2010 was only 1.4 percent. “Vaccination is not just about cervical cancers but cancers their sons will potentially get in the future.”

The dangers of HPV may sound pretty disturbing, particularly for those who might have shrugged off the virus’s threat because they believed it wouldn’t imperil them or their children. But there are a few important things to understand about HPV. First, we aren’t all doomed. A lot of scary statistics get batted around about HPV—6 million new infections a year! Half of sexually active people will get it in their lives!—but most of the 130-plus strains appear to do no damage, and most people’s immune systems recognize the handful of dangerous strains as something nasty that should be destroyed.

But an unlucky 1 percent of the population will not produce the antibodies necessary to defeat the invaders. And it is basically impossible to know whether you or one of your partners is part of that 1 percent. There isn’t a reliable blood test to tell whether your body is making antibodies against the virus and is thus protected naturally and you don’t need the vaccine.

The vaccines work best in those who have never had sex and therefore have never been exposed to any strain of the virus. That means the safety and efficacy of the vaccines are of limited comfort to those who were sexually active prior to 2006, when the vaccine first became available to females (in 2009 males were officially given the OK).

After a certain age, 26 in the United States, it is assumed most people have had enough sexual partners that they have been exposed to HPV and their bodies have produced the antibodies necessary to defeat it on their own. In the case of women who have been exposed and developed an infection, it is thought that cervical abnormalities will have been detected and dealt with. Vaccinating people after a long sexual history simply isn’t worth the cost, from a public health perspective.

But age isn’t always a reliable measure of sexual activity, particularly for those who, say, married young and are getting a divorce and re-entering the dating scene. “If you vaccinate a 45-year-old woman who hasn’t had a cervical HPV, the vaccine will work for her as well,” says Aimée R. Kreimer of the National Cancer Institute. One study shows the vaccines, which guard against multiple varieties of the virus, can be effective in older women who have not been previously exposed to all of the targeted strains. Another study even suggests that the vaccine prevents further HPV outbreaks among women who have already been treated for cervical infection. “Our findings clearly show that those who have the disease can be protected from new disease and dispels the myth that only young and virgin girls can benefit from the vaccine,” says Elmar A. Joura of the Medical University of Vienna and an author of a study published last year in the British Medical Journal. “The earlier you vaccinate the better, but the benefit never really stops. It prevents new infections for sure, independent of age.”

Unfortunately, the decision about whether to get vaccinated or not isn’t a simple one. Gardasil and Cervarix have no therapeutic properties, and once someone has caught one of the strains, the vaccine is no longer protective against that particular infection. There is no reliable blood test to show which HPV strains someone has been exposed to, so it is always possible that the vaccine could be beneficial—or not. But overall, the longer someone has been sexually active, the less likely the vaccine will be of use, which is why public health campaigns focus on the young.

Most nations with universal health care also have rigorous cost-control measures and do not cover the HPV vaccine for people in their 20s. The exact age varies: In the United Kingdom vaccinations are free for those 11 to 17 years old. In Canada, where vaccination programs are run by the provinces, free shots are chiefly available to school-aged women. The same is true in most European nations. Studies like Joura’s have inspired many countries to raise their age recommendations beyond America’s 9 to 26 years old—Canada suggests the vaccine for women up to the age of 45—but those who aren’t covered by the public vaccination programs have to pay for it themselves. “This [hypothetical older] woman is probably not cost-effective in a vaccination program, but when she is looking for the personal benefit she clearly gets it,” Joura says.

America’s patchwork of private and public providers are often more generous with free vaccinations than are health care systems in other developed nations. Many insurance companies will cover the cost of the shots for those up to the age of 26, as will many publicly funded programs for children, and in some states adults, without private insurance.

The FDA’s age-licensing limitations or the CDC’s age recommendations do not mean that it is a bad idea for those older than 26 to get the HPV vaccine. But the cost of the vaccine in most cases has to be paid out of pocket, to the tune of about $390 to $500. Is it worth it? That’s a personal judgment call. The fewer sexual partners you’ve had, the less likely it is that you’ve already been exposed to the HPV strains the vaccine defends against. If you anticipate having new partners (potentially with new virus strains you haven’t been exposed to before), you may well still benefit from the vaccine.

For people who haven’t encountered all of the HPV strains in the vaccine, says Alex Ferenczy of McGill University, “the efficacy of the vaccine is still outstanding for those remaining virus types to which they were not exposed before the vaccination.”

One more reason to consider the vaccine is that it is unclear whether antibodies, either induced by an actual HPV infection or the vaccine, have a half-life. That means protection may not last forever. This is true of other antibodies: The immunity conferred by a childhood brush with chickenpox may not last to protect us from shingles, which is caused by the same virus, later in life. It is known that vaccine-induced antibodies or those produced naturally in reaction to an HPV infection last 10 years. But they have not been proven to last a lifetime. If they don’t last, this is another possible reason why the vaccine could be effective in women in their 40s, but there is not enough research to prove or disprove this premise.

The vaccine is most useful for young people who are least likely to have been exposed. But by this measure, America is failing. Due to our long history of anti-vaccine hysteria, and some conservative politicians’ perennial efforts to politicize anything remotely related to sex, HPV vaccination rates in the United States are terribly low. Only 32 percent of girls ages 13 to 17 have received the full three-shot regimen, which is significantly less than in Canada, Great Britain, and some regions of Mexico (although much of the European Union has similarly dismal rates). Like most health issues in the United States, HPV’s worst consequences are unequally distributed, with cervical, anal, and penile cancer rates all higher among lower-income populations who tend to be poorly covered by insurance programs and have less access to health care.

For those who are under 26, getting vaccinated will likely be free. Since it is impossible to know how effective the vaccine may be in your case, it’s worth getting—it won’t hurt you or your wallet. For those over 26, vaccination can be an expensive decision, but it may well be worth it, particularly if you haven’t had many sexual partners or are expecting new ones. But to get the most bang for our public health buck, America needs to muster the political will to establish HPV vaccination programs for schoolchildren, both boys and girls. We already require vaccination of children against another sexually transmitted infection before they enter school: hepatitis B. HPV vaccination is an easy and safe way to spare kids a lot of pain and fear later in life.


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


High HPV Immunization Rates Achieved With PATH Initiative

Source: Medscape.com

August 30, 2012 (Montreal, Quebec) — Exceptionally high immunization rates against human papillomavirus (HPV) have been achieved in target-aged girls in India, Peru, Uganda, and Vietnam as a result of a PATH initiative, researchers told delegates here at the Union for International Cancer Control World Cancer Congress 2012.

Vivien Tsu, PhD, MPH, director of the HPV vaccines project at PATH, reported that a minimum of 80% — and in some countries well over 90% — of school-aged girls received at least 1 dose of the HPV vaccine in the 4 countries to which the initiative has been directed over the past several years.

“The reason the program was successful in these countries, and likely many others, is that there is visible government endorsement and involvement in the program,” Dr. Tsu explained. “For the most part, people trust that the government is trying to help them, so if the government is saying ‘this is worth doing,’ the community participates.”

As Dr. Tsu noted, cervical cancer — at least 70% of which is caused by HPV types 16 and 18 — is a major health issue for women in low- and middle-income countries, with a projected incidence in 2030 of more than 750,000 women. In North America and Europe, cytology has been extremely effective in detecting cervical cancer and, more important, precursor lesions.

However, in low- and middle-income countries, “cytology has failed to have much of an impact,” Dr. Tsu explained, because these countries lack the necessary resources to offer widespread cervical cancer screening.

Fortunately, the 2 currently available HPV vaccines (Gardasil and Cervarix) have been shown to safely and effectively protect against HPV 16 and 18, she added.

Importantly, both vaccines have also been prequalified by the World Health Organization (WHO), which is necessary for their widespread uptake. Based on WHO recommendations, girls 9 to 13 years of age are the main target group for HPV vaccination.

In an effort to demonstrate that target-aged girls can be successfully vaccinated, PATH directors rolled out 3 vaccine delivery strategies: a school-based HPV program, a community health HPV-based program, and an extension of an already existing outreach program to members of the community.

The process of “parental consent varied from country to country,” Dr. Tsu noted. In general, the Ministry of Health in each country dealt with the vaccine as they do any other vaccine. “Parents either signed an authorization allowing their daughters to be vaccinated or, if they did not want their child to be vaccinated, the child could simply say no, and they weren’t vaccinated,” she explained.

The initiative relied on a pulsed media campaign; the heavy use of radio spots during the weeks prior to immunization helped concentrate publicity.

In total, more than 66,000 young girls were eligible for the HPV program. As Dr. Tsu noted, 97% of the target age group in Vietnam received at least 1 dose of the vaccine and 96% received all 3 doses.

In India, 88% of the target group received at least 1 dose and 79% received all 3 doses. Immunization rates were also very high in Uganda, with more than 96% of eligible girls receiving 1 dose and 89% receiving all 3 doses. In Peru, more than 80% of eligible girls received all 3 doses.

“There was little difference in the coverage between strategies,” Dr. Tsu observed. “We saw that with strong community mobilization efforts and training of healthcare workers, the program can be successful.”

Dr. Tsu noted that healthcare workers who delivered the vaccine and teachers in schools where the HPV vaccine program was administered need to be trained to answer questions about the vaccine. “If the administrators don’t know the answers to [questions that are raised], they can’t inspire the confidence that is needed to make the program successful.”

A crisis communication plan also needs to be put into place to deal with any rumors that arise related to the vaccine and to dispel their potentially negative influence quickly.

Session chair Silvana Luciani, from the Pan American Health Organization, pointed out that the vaccines are “an important part of cervical cancer prevention.”

“What PATH is doing on some of its demonstration projects is really yielding critical information on the implementation of these vaccines and showing us that it is feasible, that you can attain high coverage rates. It’s one thing to have the vaccine, the actual implementation is quite another,” Luciani added.

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

August, 2012|Oral Cancer News|

Oral sex may cause more oral cancer than smoking in men, researchers say

Source: www.bloomberg.com
Author: Robert Langreth

A virus spread by oral sex may cause more cases of throat cancer in men than smoking, a finding that spurred calls for a new large-scale test of a drug used against the infection. Researchers examined 271 throat-tumor samples collected over 20 years ending in 2004 and found that the percentage of oral cancer linked to the human papillomavirus, or HPV, surged to 72 percent from about 16 percent, according to a report released yesterday in the Journal of Clinical Oncology. By 2020, the virus-linked throat tumors — which mostly affected men — will become more common than HPV-caused cervical cancer, the report found.

HPV is known for infecting genitals. The finding that it can spread to the throat and cause cancer may increase pressure on Merck & Co., the second-largest U.S. drugmaker, to conduct large-scale trials to see if its vaccine Gardasil, which wards off cervical cancer in women, also prevents HPV throat infections.

“The burden of cancer caused by HPV is going to shift from women to men in this decade,” Maura Gillison, an oncologist at Ohio State University and study senior author, said in a telephone interview. “What we believe is happening is that the number of sexual partners and exposure to HPV has risen over that same time period.”

Gillison said she worked with researchers at Whitehouse Station, New Jersey-based Merck several years ago to design a study in men. After Merck acquired Schering-Plough Corp. in 2009, though, the trial “was canceled,” she said.

No Further Study
Pamela Eisele, a spokeswoman for Merck, said the company decided not to move ahead with a big oral cancer study “due to competing research and business priorities.” GlaxoSmithKline Plc (GSK) has “no plans” to study the company’s competing vaccine Cervarix outside of cervical cancer, Jennifer Armstrong, a company spokeswoman, said in an e-mail.

Gardasil is approved for preventing cervical, vaginal and anal cancers and genital warts, and is recommended for girls and women ages 9 through 26. It is also approved for preventing genital warts and anal cancer in boys and young men of the same ages. Glaxo’s Cervarix is approved for preventing cervical cancer in females ages 9 through 25.

Both vaccines target the HPV strain linked to oral cancer, Gillison said.

HPV-linked throat cancers, or orophyaryngeal cancer, are increasing so rapidly that by 2020 there will be 8,700 U.S. cases, with 7,400 cases in men, versus 7,700 cases of cervical cancer, the study said. Male cases alone will outnumber cervical cancer cases soon after 2020, Gillison said. The Ohio State study is based on tumor samples from several U.S. states.

HPV Infections
Roughly 20 million Americans have genital HPV infections, according to the Atlanta-based Centers for Disease Control and Prevention. At least half of sexually active women and men get it at some point in their lives, the CDC says. Most of the time it doesn’t cause health problems.

Until recently, head and neck cancer mainly occurred in older patients and was associated with tobacco and alcohol use. The HPV-linked head and neck cancers, usually of the tonsils, palate or tongue, hit men their 30s, 40s, and 50s, Gillison said. It is unclear why women are affected much less often than men, she said.

The decline in HPV-negative oral cancers mirrors the decline of smoking in the U.S., the study said.

Treatment involving chemotherapy, radiation and sometimes surgery, “is very nasty,” said Gillison. “It can leave people with permanent physical disfigurement, difficulty with speech and swallowing and poor dental health.”

Research Effort
Gillison started researching the oral cancer epidemic more than a decade ago as a fellow at Johns Hopkins University. Another researcher told her about a report from Europe of a case of oral cancer that was HPV positive, she said.

“I started working on it immediately,” she said.

In a 2007 epidemiology study published in the New England Journal of Medicine, Gillison and her colleagues found that having a high number of oral or vaginal sex partners are risk factors for HPV-associated throat cancer. The cancer may also be spread by open-mouth kissing, Gillison said in the interview.

“Nobody paid attention to oral HPV infections until 2007,” she said. “We are about 15 years behind in the research” compared with the data on cervical cancer and HPV, she said.

An editorial accompanying the study concluded that trials to see whether vaccines prevent oral cancer “are needed, given that prevention through vaccination will almost certainly be the ultimate solution” to HPV-positive oral cancers.

A key step would be to perform a natural history study that would follow people over a number of years and track in more detail how HPV-oral infections lead to cancer. This could help inform how to design a vaccine trial, Gillison said.

Both vaccines target the HPV strain linked to oral cancer, Gillison said.

HPV Cancer Hits 8,000 Men, 18,000 Women a Year

Source: WebMD.com

HPV cancer isn’t just a female problem, new CDC figures show.

Although HPV causes 18,000 cancers in women each year, it also causes 8,000 cancers in men, the CDC calculates. To get the figures, CDC researchers analyzed data collected from 2004 to 2008 in two large cancer registries.

HPV, human papillomavirus, is the cause of nearly all cervical cancers. But that’s obviously not the only cancer caused by this sexually transmitted virus.

HPV also causes about two-thirds of mouth/throat (oropharyngeal) cancers, 93% of anal cancers, and more than a third of penile cancers. Men are four times more likely than women to get HPV mouth/throat cancer, while women are more likely than men to get HPV anal cancer.

Clearly, HPV is not just a female problem. Yet it was only last year that one of the two FDA-approved HPV vaccines was recommended for teen boys. Gardasil was recommended for girls in 2006; Cervarix was recommended for girls in 2009.

“HPV vaccines are important prevention tools to reduce the incidence of non-cervical cancers,” the CDC notes in a report in the April 20 issue of Morbidity and Mortality Weekly Report. “Transmission of HPV also can be reduced through condom use and limiting the number of sexual partners.”

HPV vaccines are most effective when given before people become sexually active. Yet in 2010, less than a third of teen girls had received all three doses of HPV vaccines. Numbers aren’t yet available for boys.

The slow uptake of the vaccine by teen girls is in stark contrast to the contribution HPV makes to women’s cancer risk. Taken together, HPV cancers are more common than ovarian cancers, and nearly as common as melanoma skin cancers in women.

Among men, HPV cancers are about as common as invasive brain cancers.

HPV Prevention

HPV is an extremely common sexually transmitted infection. At least half of sexually active people get HPV at some time during their lives. At any given time, more than 20 million Americans carry the virus.

Each HPV infection usually clears after a year or two. But that doesn’t always happen. Those HPV infections that persist can lead to the development of cancers.

Although condom use and limiting the number of one’s sex partners reduce HPV spread, vaccination — before a person becomes sexually active — is the surest way to prevent infection.

The Cervarix HPV vaccine protects against the two HPV strains most likely to cause cervical cancer. The Gardasil HPV vaccine protects against these and two other HPV strains.

Routine vaccination with three doses of Cervarix or Gardasil is recommended for girls aged 11 or 12. Routine vaccination with three doses of Gardasil is recommended for boys aged 11 or 12. Catch-up vaccination is recommended for females through age 26 and for males through age 21.

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

April, 2012|Oral Cancer News|

AAP Now Recommends HPV Vaccine for Boys and Girls

Source: HemOnc Today

The American Academy of Pediatrics Committee on Infectious Diseases issued an updated policy statement on human papillomavirus vaccination that recommends both boys and girls be immunized.

The policy statement notes vaccination reduces the incidence of sexually transmitted infections and reduces cancer risk.

“Persistent infection with high-risk HPV types is responsible for most cervical and anal cancers in females,” the statement reads. “In males, high-risk HPV types are responsible for a large proportion of cancers of the mouth and pharynx, which are increasing in recent years, and of anal and penile cancers.”

There currently is one approved HPV vaccine (HPV4; Gardasil, Merck) for boys and two vaccines — HPV4 and HPV2 (Cervarix, GlaxoSmithKline) — approved for girls.

The committee recommended that:

  • Girls aged 11 to 12 years should receive three doses of HPV2 or HPV4 — administered intramuscularly at 0, 1 to 2, and 6 months — even if they already are sexually active.
  • Boys aged 11 to 12 years should receive three doses of HPV4 using the same schedule.
  • Females aged 13 to 26 years and males aged 13 to 21 years who were not previously immunized or who are missing a vaccination should complete the full series.
  • Men aged 22 to 26 years who were not immunized previously or who are missing a vaccination may receive the HPV4 series, but “cost-efficacy models do not justify a stronger recommendation in this age group.”

The policy statement recommended that women who receive the vaccine continue to undergo cervical cancer screening.

About 20 million Americans currently have an HPV infection, and an estimated 7,080 men and 14,720 women develop cancers associated with HPV types 16 and 18 every year, according to the CDC.

An estimated 80% of anal cancers, 65% of vaginal cancers, 50% of vulvar cancers, 35% of penile cancers and nearly all cervical cancers are HPV-related. Roughly 60% of oropharyngeal cancers are associated with HPV.

Disclosure: The researchers report no relevant financial disclosures.

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

March, 2012|Oral Cancer News|

Canadian provinces weighing HPV vaccination of boys

Source: www.cmaj.ca/
Author: Laura Eggertson

Provinces weighing the merits of implementing the National Advisory Committee on Immunization’s recommendation to offer human papillomavirus (HPV) vaccine to boys and men aged 9–26 are facing a tricky trade-off between benefits and costs.

“I think the benefits are there, but the costs are high,” which is a crucial issue for publicly funded programs, says Dr. Monika Naus, medical director of immunization programs and vaccine-preventable diseases for the British Columbia Centre for Disease Control.

The National Advisory Committee on Immunization last month recommended extending the human papillomavirus vaccine to boys and men aged 9 to 26 “for the prevention of anal intraepithelial neoplasia (AIN) grades 1, 2, and 3, anal cancer, and anogenital warts”. The move followed on the heels of an October 2011 recommendation from United States Centers for Disease Control and Prevention advisory panel recommendation that HPV vaccine be given to boys aged 11–12 to ward off genital warts, anal cancer and “possibly” head and neck cancer.

In deciding whether to proceed, the provinces should note that “the public health and economic burden of AGWs [anogenital warts] in Canada is considerable, particularly among men whose incidence rates and incidence rate ratios compared to females have been increasing in recent years,” the committee stated.

The committee’s report also noted that the number of annual cases (and average annual incidence per 100 000) of penile cancer among men in Canada is 127.4 (1.0 per 100 000), while the number for cancer of the anus is 208.2 (1.6), oral cavity 853.1 (6.5) and oropharynx 84.3 (0.64). The estimated portion of those cancers that are attributable to HPV is 63% for penal cancer, 92% for anal cancer and 89% for both oral cavity and orapharyngeal cancer.

The committee also advised that the provinces weigh whether an HPV vaccination program for boys is preferable to campaigns designed to increase female vaccination rates.

It also cautioned provinces against making the presumption that vaccinating boys would lower cervical cancer rates among girls. “While current models predict that addition of males to a routine HPV vaccination program would prevent additional cases of genital warts and cervical cancer among females to varying degrees, this is based on assumptions that such transmission from males to females will be reduced, rather than observational data.”

Data on the economic burden of HPV is often highly conditional on a series of assumptions. The Canadian Consensus Guidelines on Human Papillomavirus issued by the Society of Obstetricians and Gynaecologists of Canada in 2007 projected the annual economic burden at $300 million, with the bulk of that — $244 million — representing the cost of “more than 9.3 million Pap tests that produce negative or false-positive results; the rest ($53.7 million) is due to true genital or cervical disease. HPV types 6, 11, 16, and 18 are thought to be responsible for 100% of the cost of genital warts ($9.2 million), 36% of the cost of CIN 1 [cervical intraepithelial neoplasia] (total cost $15.7 million), 61% of the cost of CIN 2/3 (total cost $14.5 million), and 73% of the cost of cervical cancer (total cost $13.6),” (www.hpvinfo.ca/uploads/hpvinfo.previewsite.ca/files/hpv-guideline-full_e.pdf).

The cost of a three-dose HPV vaccination, meanwhile, is generally projected to be in the neighbourhood of $450–$500. That can quickly add up, as evidenced by the decision to vaccinate girls aged 11–14, which in 2007 resulted in a federal government allocation of $300 million over three years.

Whether the federal government might provide a similar chunk of funds to vaccinate boys is unknown, says Dr. John Spika, director general of the Public Health Agency of Canada’s Centre for Immunization and Respiratory Infectious Diseases.

Naus notes that lower incidence rates of oral, anal and penile cancer, as compared with cervical cancer, make it much harder to justify the outlay of tax dollars for a generalized campaign for boys. She also indicated the provinces are awaiting the findings of a Public Health Agency of Canada commissioned cost–benefit analysis of HPV vaccination of boys expected to be completed this spring.

The provinces must also grapple with the advisory committee’s precaution that a program for boys must be weighed against measures designed to increase vaccination take-up by girls.

The Federation of Medical Women of Canada argues that vaccinating boys makes sense when there is a low uptake among girls, so it urges gender equity in the funding of HPV vaccination.

If a prove has less than an 85% uptake among girls, there is a benefit to immunizing both sexes, says Dr. Vivien Brown, a member of the federation’s board. “You cannot eradicate disease by simply vaccinating one sex,” Brown says. “We don’t have fantastic uptake of vaccine in women.”

Naus notes that the vaccination rate among eligible girls in BC is now 70% and climbing annually at a rate of 5%. But Brown notes the rate is only 55% in Ontario.

The provincial government is awaiting advice from Public Health Ontario before deciding whether to provide HPV vaccination of boys, says David Jensen, a spokesman for the province’s Ministry of Health and Long-Term Care, while Quebec is awaiting advice from its public health institute, says Stephanie Menard, a spokesperson for the Quebec Ministry of Health and Social Services.

Spika says another major consideration is whether the intent of a vaccination program will be to prevent only HPV-related cancers, or all HPV infections.

Both the Canadian and US advisory panels recommended against the use of one of those vaccines (Cervarix) for boys, on the grounds that its efficacy has not yet been proven.

Cervarix is not yet approved in Canada for use in boys but if it does become available and a province chooses to target only cancer-causing strains of HPV, that might reduce costs, Spika says. “Obviously, it’s a competitive process, and having two products on the market is better than one.”

No decisions are expected to be taken by provinces until the Canadian Immunization Committee, which represents provincial governments, finalizes its position on the issue.

February, 2012|Oral Cancer News|

Success of HPV vaccination is now a matter of coverage

Source: The Lancet Oncology, Volume 13, Issue 1, Pages 10-12, January 2012

In a pair of articles in The Lancet Oncology, Lehtinen and colleagues and Wheeler and colleagues present 4-year end of study data from a trial of a prophylactic human papillomavirus (HPV)-16/-18 vaccine (Cervarix, GlaxoSmithKline) in young women aged 15-25 years. From a public-health perspective, these studies have several important contributions.

The results assure us that among HPV-naive women in the 15—25 year age range, Cervarix has extremely high efficacy against HPV-16/-18-associated persistent infection, CIN2, and CIN3 or worse, the best ethical surrogate endpoint for prospective studies of invasive cervical cancer risk. Combined with other trials of Cervarix and Merck’s quadrivalent Gardasil vaccine against HPV-16/-18/-6/-11,3 the evidence is strong for near 100% prophylactic vaccine efficacy in HPV-naive women at any age.

Nonetheless, even with vaccine efficacy near 100% in HPV-naive women, the efficacy in the total vaccinated cohort decreased steeply with increasing age, showing an absence of therapeutic effect against already-acquired infections and associated lesions. We know from natural history studies that new HPV transmission (incidence, not prevalence) decreases with age in most cultures.4 Together, natural history data and results of trials for both vaccines suggest that vaccination before sexual debut, or around the time of menarche, will achieve the greatest reduction in cervical cancer rates.

The 4-year trial data shows no decline in vaccine efficacy in HPV-naive women with time since vaccination.1 We know from other trials of the two vaccines that the duration of protection is several years longer than that shown in the present trial.5 Sustained increased antibody titres and absence of breakthrough HPV-16/-18 outcomes in progressively longer follow-up of vaccinated cohorts are encouraging signs; even without boosters, protection for 10—15 years after primary immunization would prevent HPV-16/-18 infection at its peak incidence, lead to a sharp reduction in the secondary peak incidence of precancers, and eventually provide a proportional reduction in cancer. Life-long immunity is not a requirement for vaccine success, in view of the typically long latency between HPV acquisition and cancer outcome. With current vaccines administered at perimenarche, protection against HPV infection might last long enough to prevent most cervical cancers in that birth cohort.

The substantial cross-protection Cervarix provides against some other oncogenic types, especially against HPV-31/-33/-45, increases its effectiveness for prevention of pre-cancer and cancer, beyond the more limited cross-protection reported for Gardasil. The optimistic predictions about HPV vaccination are confirmed: we now know that Cervarix and Gardasil can have substantial public-health benefit. High coverage with Cervarix or Gardasil vaccination would probably prevent a substantial numbers of cancers, as the investigators note for Cervarix. Data from randomised trials and post-licensure monitoring support decisions by public-health agencies that both vaccines are generally safe and effective, although more extensive safety data to rule out rare or late adverse events are needed and pending. Either vaccine will likely not only prevent cervical cancer, but also a substantial proportion of vulvar and vaginal cancer, anal cancer,6 and possibly oropharyngeal cancer.

Now that Cervarix and Gardasil are proven effective, licensed, and in broad use, what remaining HPV-vaccine-related public health questions are most important? The choice of vaccine might be more of a commercial battle than a crucial public-health issue. The two vaccines are slightly different in preparation and activity. On the one hand, possibly because of its novel adjuvant, Cervarix shows increased cross-protection and generates higher antibody titres than Gardasil after vaccination. We are not sure whether higher titres immediately after vaccination lead to longer duration of protection, and do not know if cross-protection will last as long as protection against the targeted HPV types. On the other hand, Gardasil provides important population coverage against genital warts. Both vaccines are beneficial and it is difficult to decide between them. Universal uptake of vaccination with Cervarix, the present version of Gardasil, or a nine-type version of Gardasil that is in final trials, which protects against seven oncogenic types (HPV-16/-18/-31/-33/-35/-52/-58) plus HPV-6/-11, would likely prevent more than two-thirds of cervical cancers.

Accordingly, we believe that increasing coverage, particularly of sexually-naive adolescent females, is now the most important public-health issue in HPV vaccine efforts. Based on the aggregate data, including those presented by Lehtinen and colleagues and Wheeler and colleagues, we advocate focusing vaccination efforts in this core population to reduce cervical (and other) cancers. The irrefutable public-health benefit from a concerted effort to vaccinate adolescent females need not await resolution of contentious questions of whether to initiate catch-up or mid-adult female vaccination, or a decision on whether Gardasil is cost-effective for adolescent males, among whom vaccination might reduce HPV-related oropharyngeal, penile, and anal cancers.

We are particularly concerned about low vaccination rates in areas where cervical cancer incidence and mortality are high because of inadequate alternative prevention through effective cervical screening, and where nine of 10 cervical cancer deaths occur. Needed new developments that would promote vaccine coverage in these areas, and globally, include an inexpensive HPV vaccine, a formulation that does not require a cold chain to keep the vaccine frozen until administration, or a vaccine that requires only a single dose. The current vaccines are too expensive and difficult to deliver for many low-resource regions. Based on strong immunogenicity in younger adolescents, some regions in Canada and Mexico have decided to administer only two doses of vaccine, with plans to evaluate ongoing efficacy 5—10 years later. New evidence suggests that two doses of Cervarix provide adequate protection against HPV-16/-18 for at least 4 years; comparable data for Gardasil have not yet been presented.

Long-term proof of the safety of HPV vaccines is a public-health priority; uptake will increase as public trust in vaccine safety increases. One safety issue that would benefit from more data (currently being collected) is whether there is any link between vaccination during early pregnancy and miscarriage.
The exciting proof-of-principle phase of vaccine development is over. The practical aspects of vaccine uptake are now the most important issue in HPV vaccine research from a public-health perspective. Increasing uptake through further technological refinements and adaptations to regional circumstances will be the most effective ways to achieve wide-scale high coverage and fulfill the promise of HPV vaccination.

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













January, 2012|Oral Cancer News|

Boys need the cervical cancer jab, too

Source: www.telegraph.co.uk
Author: Max Pemberton

Few politicians will ever admit they are wrong, so I salute health ministers who have finally capitulated to medical opinion and last month announced a U-turn on the cervical cancer vaccine that is given to 12- and 13-year-old girls.

Until now, Cervarix, which protects against two strains of the human papilloma virus (HPV) that are a factor in at least 70 per cent of diagnoses, has been the NHS vaccine of choice. However, another vaccine, Gardasil, also protects against a further two strains of HPV which cause genital warts, the most common sexually-transmitted infection, requiring costly and unpleasant treatment.

As doctors have been arguing for some time, this has important public health implications. The current cost to the NHS of treating the 100,000 new cases of genital warts in England each year is £23 million. In several countries, including Australia, where Gardasil has been used in nationwide vaccination programmes, a 75 per cent decrease in the number of new cases of genital warts in the past three years has been reported.

Critics of NHS policy complained that Cervarix was chosen over Gardasil not on the basis of clinical efficacy but because its manufacturers offered it at a discounted price, making it the most cost-effective. Indeed, many doctors have admitted in the medical press that they have bought Gardasil for their daughters privately, while they had to give their patients Cervarix. But ministers have seen sense as now Gardasil will be available on the NHS.

But the battle against HPV has not been entirely won with this volte-face. Many doctors and public health officials believe that it is not only girls who should be protected. Gardasil prevent warts, but there is also emerging evidence to suggest that it can protect against other cancers caused by HPV, such as anal and penile cancers. And a study published in The New England Journal of Medicine showed that those infected with HPV were 32 times more likely to develop oral or throat cancers. This finding dwarfs the increased risk associated with two acknowledged factors for developing these cancers: smoking (three times more likely to develop cancer) and drinking (2.5 times). Research published last month in the Journal of Clinical Oncology found that HPV now accounts for more head and neck cancers than tobacco or alcohol.

December, 2011|Oral Cancer News|