HPV Cancers Increase, Vaccination Rates Remain Low

Roxanne Nelson

January 09, 2013

A rise in cancers associated with human papillomavirus (HPV) in the United States is highlighted in the Annual Report to the Nation on the Status of Cancer, which was published online January 7 in the Journal of the National Cancer Institute. The authors of the report, as well as other experts, have used these data to emphasize the potential of the HPV vaccination.

The report shows that overall cancer death rates continue to decline in the United States, as do the incidence rates of some, but not all, types of cancer. In fact, incidence rates are increasing for HPV-associated oropharyngeal and anal cancers, and HPV vaccination coverage in the United States remained low in adolescent girls in 2008 and 2010.

Vaccine Coverage Low in the United States

In 2010, 32.0% of American girls 13 to 17 years of age had received 3 doses of the HPV vaccine. Coverage was significantly lower than the national average in those without insurance (14.1%). It was also significantly lower in some of the Southern states (20.0%), which have the highest rates of cervical cancer and the lowest prevalence of recent Pap testing.

"Failure to reach high HPV vaccination coverage among key subgroups with low future screening participation and/or high-risk sexual behavior may result in substantially lower population-level effectiveness and may increase inequalities in the burden of HPV associated cancers," write Marc Brisson, PhD, from the Centre de recherche du CHU de Québec, in Quebec, Canada, and colleagues in an accompanying editorial.

They point out that overall, HPV vaccination coverage is low in the United States, and coverage tends to be even lower in states with a lower level of cervical screening and higher sexual activity.

HPV-associated cancers diagnosed in 2009 accounted for 3.3% all cases of cancer in women and 2.0% in men. Cervical cancer accounts for 32.7% of all HPV-associated cancers and for 53.4% of all HPV-associated cancers in women.

Oropharyngeal cancer accounts for 78.2% of HPV-associated cancers in men and in 11.6% of HPV-associated cancers in women. In men and women combined, it accounts for 37.3% of HPV-associated cancers.

"In Australia, at 70% coverage, females-only HPV vaccination has substantially reduced anogenital warts not only among female cohorts targeted for vaccination (>90% reduction), but also among young heterosexual men (>80% reduction) and older heterosexuals of both sexes," the editorialists write. "Such high levels of direct protection and herd immunity are very promising for population-level effectiveness against HPV-associated cancers and reductions in inequalities in countries with high HPV vaccination coverage," they add.

But they caution that in countries where vaccination coverage is low, inequalities in HPV-associated diseases may increase, even if vaccine coverage is equal across all socioeconomic and racial/ethnic groups.

Too Early to Show Oral Effects

It is too early to see an effect of the vaccine on cancers of the oropharynx. "The vaccine has not yet been shown to reduce the rate of head and neck cancers," said Amy Leader, PhD, assistant professor of oncology at Thomas Jefferson University in Philadelphia, Pennsylvania.

"Right now, we are able to show the predominant associations between the oral cancers and the types of HPV that are present in those cancers," she told Medscape Medical News. "They are the same predominant types — 16 and 18 — that are contained in the vaccine," she explained.

"The thinking is that because the cancers are caused by such a prevalent strain (which is contained in the vaccine), over time, we will see a reduction," Dr. Leader said. "We are all very hopeful."

The increase in cancers of the oropharynx could be arising from baby boomers who were infected long ago with HPV, she explained. "This group is...now at the 'cancer age,' so to speak, and these are the people who are developing cancer right now," she noted.

"These patients may have been infected at the height of their sexual activity, and now, 20 or 30 years down the road, we are seeing cancer," she added.

Vaccination isn't going to help this population; the idea is to vaccinate the next generation to reduce the incidence of these cancers. "But the effects of the vaccine are not going to be seen for a while. This is a very long-term commitment, because oral cavity cancers and oral pharyngeal cancers tend to take a while to develop," said Dr. Leader.

The fact that oral cancers are 2 to 3 times more prevalent in males than females "really emphasizes the importance of getting the males vaccinated," she noted.

Although disparities exist in the United States, the overall rate of cervical cancer dramatically declined in the era of widespread Pap testing. It is not known whether the rate will decline further with the vaccine. "From a public-health standpoint, we would always like to say it can go lower," explained Dr. Leader. "The best-case scenario is that we will have zero cases, although we know that will never happen. I think we all have a sense that the 'biggest bang for the buck' will be in underdeveloped nations, where women do not have easy access to Pap screening," she added.

Coverage Lower Than in Other Countries

The report, coauthored by researchers from the American Cancer Society, the Centers for Disease Control and Prevention, the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries, used data drawn from the National Program of Cancer Registries and/or the Surveillance, Epidemiology, and End Results (SEER) database.

In 2010, 48.7% of girls of 13 to 17 years of age had received 1 or more doses of the vaccine; only 32.0% had received the 3 recommended doses.

This national 3-dose coverage estimate falls well short of the Healthy People 2020 target of 80%, note the authors. They point out that the 2010 uptake rate of 48.7% is much lower than the rates reported in Canada (50% to 85%) and the United Kingdom and Australia combined (more than 70%).

The low overall uptake in the United States is likely due to a number of issues, the authors report, including inadequate provider recommendations, provider reimbursement concerns, and the infrequent use of reminder/recall systems that would foster completion of the 3-dose series.


There is also variation in vaccine uptake among individual states. For 1 or more doses of the vaccine, coverage ranged from 28.8% in Idaho to 73.0% in Rhode Island; for 3 doses, it ranged from 17.6% in Idaho to 55.1% in Rhode Island; and for the 3-dose series completion, it ranged from 47.4% in Alabama to 87.1% in New Hampshire.

However, in most states from 2008 to 2010, the overall initiation of the HPV vaccination series increased significantly, by 11.5%, and receipt of 3 doses rose by 14.1%

In 2010, vaccine coverage was primarily in females; coverage in boys was only 1.4%. But routine HPV vaccination was recommended for boys in December 2011, and the authors believe that coverage will likely increase in the coming years. "This could substantially improve the overall herd immunity against HPV infection in view of the existing low vaccine uptake among adolescent girls," they write.

"This year's report correctly and usefully emphasizes the importance of HPV infection as a cause of the growing numbers of cancers of the mouth and throat, the anus, and the vulva, as well as cancers of the uterine cervix, and the availability of vaccines against the major cancer-causing strains of HPV," said NCI director Harold Varmus, MD, in a statement.

"The investments that we have made in HPV research to establish these relationships and to develop effective and safe vaccines against HPV will have expected payoffs only if vaccination rates for girls and boys improve markedly," he said.

J Natl Cancer Inst. Published online January 7, 2013. Full text, Editorial.