Tag Archives: HPV

Can HPV Vaccination Be Simplified?

The human papillomavirus vaccine was recommended for routine use in 11-12 year old girls in 2007. But by 2010, the most recent year for which data are available, less than half had received one dose of the three-dose series and fewer than a third had received all three. The inconvenience of the need for three separate office visits along with the vaccine’s price – about $130 per Gardasil dose, as of July 2011 – have certainly contributed to the low uptake.

©BVDC/Fotolia.com

Now, some parts of the world – including Mexico, Switzerland, and parts of Canada have moved to either a two-dose schedule, or a so-called “extended dose” schedule, in which the third dose is delayed until 5 years after the second one. (In the current U.S. three-dose schedule, doses two and three are given at 2 and 6 months, respectively, after dose one.)

“There has been emerging interest in HPV vaccine schedules with fewer than three doses, for a variety of reasons. These schedules could facilitate implementation, they may be more convenient for providers, parents, and vaccinees, and of course they would be cost-saving,” said Dr. Lauri Markowitz, of the Centers for Disease Control and Prevention, at a recent meeting of the CDC’s Advisory Committee on Immunization Practices.

No data on the efficacy of fewer than three doses have been published by either Merck or GlaxoSmithKline from their pivotal trials of Gardasil and Cervarix, respectively. But some other data are available for both vaccines. A nonrandomized study in Costa Rica that included more than 1,100 women who had received just one or two doses of Cervarix suggested that two doses or maybe even just one – could be as protective as three doses against infection at 4 years.

And in an as-yet unpublished study done in Canada, immune responses against both HPV 16 and 18 at 3 years were similar between two doses of Gardasil given at age 9-13 years and three doses given at age 16-26 years. But, there are limited efficacy data and no long-term data, Dr. Markowitz said.

Electron micrograph of human papillomavirus (HPV) / Courtesy of the National Cancer Institute

In an e-mail, Deb Wambold of Merck Vaccines said that, while the company does support studies of alternative dosing schedules for HPV vaccination including two-dose regimens, so far those studies are “interesting preliminary explorations in select subpopulations of vaccinees,” and “It is important to note that there are no data on the clinical efficacy or durability of effectiveness with two doses of either of the HPV vaccines, as we have for the recommended three-dose vaccination regimen.”

Dr. Joseph A. Bocchini Jr., who chairs the ACIP HPV vaccine working group, concurred. In an interview at the ACIP meeting, he noted that the long-term efficacy of two doses is “worth looking at,” as is the varying of three-dose schedules. “But, at this point, there are too few data to apply this to recommendations in the United States.”

More data from ongoing trials will be available in the next few years, Dr. Markowitz said.

-Miriam E. Tucker (@MiriamETucker on Twitter)

Advertisements

Leave a comment

Filed under Allergy and Immunology, Epidemiology, Family Medicine, IMNG, Infectious Diseases, Internal Medicine, Obstetrics and Gynecology, Oncology, Pediatrics, Primary care, Uncategorized

HPV Changes the Face of Head/Neck Cancer

Just a few years ago, tobacco and alcohol use were presumed to be the main causes of head and neck cancers. Evidence of oropharyngeal cancer associated with human papillomavirus (HPV) first appeared about 10 years ago, but it wasn’t until 2010, with the publication of 2 papers showing far greater survival among HPV-positive patients with head and neck cancer, that oncologists suddenly realized that they were likely dealing with two distinct diseases.

“It’s become clear that the disease we thought was one disease related to tobacco and alcohol is now being parsed into two major categories,” Dr. Maura L. Gillison said last week in Phoenix at the 2012 Multidisciplinary Head and Neck Cancer Symposium. At the meeting, she presented her group’s data showing that the overall prevalence of oral HPV infection in people aged 14-69 years is 6.9%, and that the prevalence is much higher among men than women. The Merck-supported trial paper was published online in JAMA on January 26, coinciding with her presentation.

Tissue section from a head and neck cancer patient / Courtesy of Tom Carey, Ph.D.

In a separate talk, Dr. Gillison summarized previous work from her group showing that the incidence of HPV-related cancer is rising while HPV-negative cancer is declining, consistent with the decline in tobacco use and changes in sexual behavior that increase HPV transmission. Overall survival of head and neck cancer has improved over the last decade, a trend that is likely due both to the improved prognosis among HPV-positive patients and to the decline in tobacco use rather than to advances in treatment, she said.

This recently heightened role of HPV in head and neck cancer  – and the awareness of it – has impacted the field of oncology in several ways. For one, it has dramatically changed the way research is done, conference chair Dr. Ezra Cohen told me. “It has made a tremendous difference in the way clinical trials are conducted, because it makes absolutely no sense to lump these patients together. Now all clinical trials will either stratify for HPV status or design completely separate studies, because they truly are two biologically different diseases.”

Clinically, patients with head and neck cancers are now routinely tested for HPV. This wasn’t the case prior to 2010. And those who test positive are counseled differently, since their prognosis is better. Indeed, Dr. Cohen said, HPV-positive head/neck cancer patients appear to respond better to just about every type of treatment, including surgery.

What’s more, Dr. Gillison told me, HPV has essentially upended some of the tools oncologists use to predict outcomes in head and neck cancer patients. One example is the current tumor staging system, which doesn’t take into account HPV status. A Stage 3 or 4 cancer which carries a poor prognosis among HPV-negative patients might carry the prognosis now associated with Stage 1 cancer among those who are HPV-positive. And another factor that has been shown to predict poor outcome in HPV-negative patients, the presence of extracapsular extension, appears to have little impact in those who are HPV-positive.

“So all these things that we take as firmly established and drivers of treatment decisions in this new setting are all in question,” she said.

Tissue section from the same head/neck cancer, with brown stain of an HPV marker protein called p16 / Courtesy of Tom Carey, Ph.D.

Thus far there have been no major changes in treatment, but Dr. Cohen believes that is likely to change as more data become available. He is currently leading a clinical trial  in collaboration with Novartis Pharmaceuticals looking at treatment with reduced radiation doses – and thereby reduced toxicity – for patients who have a good response to induction chemotherapy. Such patients are usually HPV positive.

Another study, funded by the National Cancer Institute, randomizes HPV positive patients to radiation combined with either chemotherapy or a monoclonal antibody, with the hypothesis that the latter will be better tolerated.

Dr. Cohen cautioned that treatment changes won’t come immediately. “Many of us in the field believe that there will be different therapies developed for [HPV-positive] patients, but it takes time to do that. It’s hard to make those changes, especially when we are curing the majority of these patients.”

-Miriam E. Tucker (@MiriamETucker on Twitter)

1 Comment

Filed under Allergy and Immunology, Family Medicine, Geriatric Medicine, IMNG, Infectious Diseases, Internal Medicine, Neurology and Neurological Surgery, Oncology, Ophthalmology, Otolaryngology, Primary care, Uncategorized

Got an STD? Call CDC

Doctors, your patients want to know about sexually transmitted diseases.

courtesy of Wikicommons user Metju

They might not feel comfortable asking you about STDs, but you can take comfort in the fact that many of them are going to the Centers for Disease Control and Prevention for information and not some dubiously credible resource.  

 During 2010, 44,339 STD-related phone calls were made, and 2,123 STD-related emails were sent to CDC-INFO, the CDC’s national contact center. Data on the STD-related calls and emails were presented in a poster at the biennial meeting of the International Society for Sexually Transmitted Diseases Research.

Primary care physicians, take note: The most common STD question to the CDC was, “Can you help me locate an STD testing site in my area?” Are there ways you can make this information available to patients in your office in a way that protects their privacy, perhaps with a stack of handouts listing STD testing sites in your area or a notice on the bulletin board in your waiting room?

 The most common telephone questions were about herpes (34%), STD testing and counseling (25%), and HPV (18%). The most common email questions were about herpes (34%), HPV (21%), and other STDs (12%).

CDC-INFO was established in 2005, and these findings suggest that it is serving its purpose as a useful resource. In a 2009-2010 satisfaction survey of 199 individuals who used the service, 91% said they learned new information, and 68% said they were interested in changing a behavior (most often a risky sex behavior) based on that information.

CDC researcher Dr. Rachel Kachur and colleagues noted that the phone and email STD data correlate with data from the Division of STD Prevention website , where genital herpes and HPV pages are the most visited.

You want to give your patients the information they need, and you know they won’t always ask. But let the CDC lend a hand. Even a small card saying that CDC-INFO is a resource for any and all health issues might coax shy patients to a safe, reliable resource.

Heidi Splete (on twitter @hsplete)

Leave a comment

Filed under Family Medicine, IMNG, Infectious Diseases

Oh Boy, Another Vaccine Conundrum

Should the human papillomavirus (HPV) vaccine Gardasil be recommended for routine use in boys aged 11-12 years, as it is now for girls? Or should the vaccine’s use in boys remain an option but not a routine recommendation? Alternatively, should it be routinely recommended for males who have sex with other males, a group that is at increased risk for anal infection and cancer due to HPV?

Policy decisions regarding vaccine use are often complex and nuanced, even for vaccines that aren’t already as controversial as Gardasil. The issue of vaccinating males is causing headaches for the panel tasked with making the decision, the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention.

Pat Ramsey photo via Flickr Creative Commons

Of the two HPV vaccines on the U.S. market, only Gardasil is licensed for use in males. It contains four strains of HPV, two (16 and 18) that are associated with cervical and other types of anogenital and oral cancers, and two (6 and 11) that are associated with genital warts. In December 2010, the Food and Drug Administration added the indication of prevention of anal cancer due to HPV vaccine strains in both males and females.

In 2009, ACIP said that Gardasil could be given to males aged 9 through 26 years, but didn’t make a routine recommendation. Some are now in favor of doing so, arguing that the vaccine protects males against both genital warts and anal cancer, it reduces HPV transmission to females by preventing infection in their male sex partners, and it’s simply more equitable and convenient for physicians to offer the vaccine to both male and female patients.

The main argument against the move is the vaccine’s cost, approximately $360 for the full three-dose series. A CDC-commissioned cost-effectiveness analysis posed a conundrum: Use of Gardasil in males is more cost-effective the less it is used in females, and vice versa. At current female coverage levels – just 27% for all three doses among 13- to 17-year-olds in 2009 ¬ use of the vaccine in males makes the cost-effectiveness cut-off in some models, depending on assumptions. But of course, public health officials are hoping that coverage among females will increase.

Restricting Gardasil’s use to males who have sex with males would dramatically increase the vaccine’s cost-effectiveness, as anal cancer in that group is actually more common than is cervical cancer among all women. While the vaccine’s use could certainly be promoted among older male teens and young adults who are already “out,” screening for sexual orientation among 11- to 12-year-old boys is unlikely to be a viable option.

A vote on this is likely to come later this year, but it won’t be an easy one, ACIP working group chair Dr. Janet A. Englund told me at the panel’s meeting last week in Atlanta. “The concern about cost and cost-effectiveness is a very important consideration for the committee.”

-Miriam E. Tucker (@MiriamETucker on Twitter)

Leave a comment

Filed under Allergy and Immunology, Dermatology, Family Medicine, Health Policy, IMNG, Infectious Diseases, Internal Medicine, Obstetrics and Gynecology, Oncology, Pediatrics, Primary care, Uncategorized

Hooray for Basic Science!

Telomere Staining courtesy of the U.S. Dept. of Energy

Telomere Staining courtesy of the U.S. Dept. of Energy

With all of the commotion over health care reform these days, today’s announcement that the 2009 Nobel prize for physiology or medicine has been awarded to Elizabeth H. Blackburn, Ph.D., Carol W. Greider, Ph.D.,  and Jack W. Szostak, Ph.D., for their discovery of telomeres and the related enzyme telomerase, serves as a timely reminder of the importance of basic research to medicine.

According to the official Nobel press release: “Elizabeth Blackburn and Jack Szostak discovered that a unique DNA sequence in the telomeres protects the chromosomes from degradation. Carol Greider and Elizabeth Blackburn identified telomerase, the enzyme that makes telomere DNA. These discoveries explained how the ends of the chromosomes are protected by the telomeres and that they are built by telomerase.”  

The findings have important implications for aging and cancer but the origins are humble.  Dr. Szostak and Dr. Blackburn conducted their research with single-celled organisms from pond water (Tetrahymena) and yeast.  Notably, none of the three researchears are clinicians.

A look at the last 10 years’ worth of Nobel prizes in physiology and medicine shows that the Royal Swedish Academy of Sciences seems to favor basic science research in medicine.  Only the awards in 2008 and 2005 have obvious clinical ties—HIV/HPV and Helicobacter pylori.  The other award recipients have opened up our ability to modify genes using embryonic stem cells, allowed us to see inside the body without picking up a scalpel, and better understand how the nervous system works.

So, ladies and gentlemen, can we have a round of applause please, for all of those unrecognized basic science researchers quietly slaving away over petri dishes, microscopes and chemical assays? 

—Kerri Wachter, @knwachter on Twitter

Bookmark and Share

1 Comment

Filed under Genomic medicine, Geriatric Medicine, Medical Genetics, Oncology