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)

Whose Rights Are at Stake?

The Supreme Court heard arguments Tuesday in support of the 2007 Vermont statute limiting the release of the information detailing which drugs doctors prescribe. This information is maintained by pharmacies, which sell it to data-mining agencies, that in turn sell it to drug companies, for marketing purposes. Patient information is excluded from the data, doctor’s information is not.

Under the Vermont law, this information can be released only with the consent of the doctor. However, once data collection firms like IMS Health and interested parties like Pharmaceutical Research Manufacturers of America, challenged the statute, the issue became a question of free speech.

In the case of Sorrell v. IMS Health Inc., data-mining firms claim they have First Amendment rights to buy and sell the information for their marketing use.

However, the state’s attorney’s office likened the release of the confidential information to disclosing a doctor’s tax returns, patient files, or a competitor’s business information, arguing that First Amendment rights in the case apply to protecting doctor’s information. But since the information is given away to parties including insurance companies, journalists, and law enforcement, the court wasn’t too convinced.

” … just don’t tell me that the purpose is to protect their privacy,” said Justice Antonin Scalia. “[A doctor’s] privacy isn’t protected by saying you can’t sell it but you can give it away.”

Justice John Roberts said Vermont is trying to reduce health care costs by “censoring” information doctors hear about brand-name drugs, with the intent that they will prescribe more generics, a measure Justice Scalia added was a restriction on free speech.

Vermont Assistant Attorney General Bridget Asay responded that “the purpose of the statute is to let doctors decide whether sales representatives will have access to this inside information” on the prescribing habits of physicians.

Attorneys general of several states, the federal government, AARP, medical associations, privacy groups, and the New England Journal of Medicine have filed briefs in support of the Vermont statute, according to a brief by Cornell (N.Y.) University Law School. The National Association of Chain Drug Stores, the Association of National Advertisers, the Associated Press, and Bloomberg have filed in support of the data mining firms.

In an age in which personal data can mined through social networks and search engines, this case could set the precedent concerning how much personal information can be used for marketing. A decision is expected by June.

 Tell us what you think. 

–Frances Correa (@FMCReporting on Twitter)

More Angst from ACCORD

If you prefer your large, randomized clinical trial results to be clear, consistent, and readily clinically applicable, don’t look to (ACCORD).

The initial ACCORD (Action to Control Cardiovascular Risk in Diabetes) findings shocked everyone. One arm of the trial had to be stopped a year and a half early, in February 2008, because of an unexpected 22% increased risk of mortality among the patients with longstanding type 2 diabetes and risk factors for cardiovascular disease randomized to intensive treatment aiming for near-normal glucose control (hemoglobin A1c less than 6.0%). Experts are still struggling to explain why.

Retinopathy image courtesy of Heidelberg Engineering

While ACCORD was the first trial to show increased mortality with intensive glycemic control, it was one of several to show lack of cardiovascular benefit. But some of those other trials still demonstrated a reduction in microvascular—eye, kidney, and nerve—complications with intensive glycemic control. Surely, ACCORD would at least fall in step there, no?

Um, not quite. Data presented at the annual Scientific Sessions of the American Diabetes Association and published simultaneously in the Lancet and the New England Journal of Medicine were unsatisfyingly mixed.

On the one hand, intensive control did reduce retinopathy progression, Dr. Emily Chew reported.

But at the time the intensive arm of ACCORD was stopped, there was no difference between groups in pre-specified combined endpoints of severe kidney disease, retinopathy, and neuropathy, Dr. Faramarz Ismail-Beigi reported. Certain individual endpoints, such as the development of microalbuminuria and cataract extraction, were improved with intensive control but others, like loss of vibratory sensation, showed no difference.

So what should the clinician do? At a press briefing, speakers tried to offer advice. Dr. Sue Kirkman of the ADA said intensively treating type 2 diabetes soon after diagnosis and before the development of complications may be beneficial, whereas attempting to aggressively treat once complications have developed may not help and might actually hurt. “It speaks to individualization,” she said.

Dr. Denise Simons-Morton added that one aspect of individualization is the concept of “patient-centered care,” in which the physician and patient determine treatment goals together. Some patients may be more willing to work on blood glucose control to prevent eye disease, whereas others may have concerns about doing that.

Dr. Hertzel C. Gerstein noted that although aiming for perfect blood sugar now appears to be inappropriate in patients similar to the ACCORD population, there is still evidence of benefit in aiming for the currently recommended targets of less than 7.0% or less than 6.5%.

“No clinical trial is going to tell you how to manage the person sitting across the table from you,” Dr. Gerstein said. Certainly not ACCORD, anyway.

-Miriam E. Tucker (@MiriamETucker on Twitter)

I See What You Mean

From the annual meeting of the Heart Rhythm Society, Denver:

Physicians planning to attend the upcoming annual meetings of the American Academy of Family Physicians, Society of Diagnostic Medical Ultrasound, or American Public Health Association at Denver’s Colorado Convention Center should prepare themselves for Shock and Awww when they encounter the big blue bear, a whimsical 40-foot tall sculpture peering through the glass to see what’s going on inside.

The sculpture by British-born University of Denver artist Lawrence Argent  is titled, “I See What You Mean.” Commissioned under the city’s 1%-for-public-art program, the big blue bear weighs 10,000 pounds and is composed of more than 4,000 polymer and concrete interlocking triangles over a steel frame. Argent began with a small plastic toy he scanned and converted into a digital computer file, which he then sculpted electronically.

The big blue bear has become a popular, feel-good tourist attraction. It also serves as a convenient meeting point for conventioneers who become disoriented by the conference center’s long, white, largely unmarked corridors.

— Bruce Jancin

Photo by Bruce Jancin

Hospitals Moving “Moo” Off the Menus

(Courtesy NASA Goddard Space Flight Center)

Here’s a happy Earth Day item: Four hospitals in the San Francisco Bay Area reduced their meat purchasing for menus by 28% in a pilot study, thereby avoiding significant amounts of associated greenhouse gas emissions and saving hundreds of thousands of dollars in costs.

Most of the drop in greenhouse gases came from reduced purchases of beef, which is a notorious producer of gases that contribute to global warming.

The study is the first attempt to evaluate the “Balanced Menus” program, which was created by the San Francisco Bay chapter of Physicians for Social Responsibility and has been rolled out to 32 hospitals across the United States by the nonprofit organization Health Care Without Harm. The Johns Hopkins Center for a Livable Future partnered with Health Care Without Harm to conduct the study.

A hospital meal (not in one of the study hospitals) by flickr user VirtualErn (Creative Commons).

Two hospitals reduced meat (beef, pork and chicken) in its cafeterias or cafes, one hospital reduced meat in inpatient menus/meal services, and one hospital did both. The Balanced Menu program also had them try to replace the remaining meat on their menus with purchases from sustainable and grass-fed meat producers instead of industrialized meat sources.

The study estimated that in a year’s time, the reduced meat purchases would avoid a total of 1,004 tons of carbon dioxide-equivalent greenhouse gas emissions. That’s roughly equivalent to not using 102,454 gallons of gasoline, or growing 23,354 tree seedlings for 10 years. Although the study did not account for greenhouse gases associated with whatever food replaced that meat, no food makes gas like beef, so there’s no doubt the planet came out ahead.

They also calculated that the less-meat, better-meat program saved the four hospitals $21,080 per month in costs even after including increased purchases of fish and vegetable sources of protein. My calculator suggests that’s $252,960 per year.

What about the patients? No complaints there, only anecdotal reports of compliments. Plus changing the meat-heavy U.S. diet could help combat rising rates of diabetes, obesity, and some cancers. According to Department of Agriculture statistics, the U.S. food supply contains 58% more red meat and chicken (8.7 ounces per person per day) than is called for in dietary guidelines that cover meat, poultry, nuts, beans, and eggs (5.5 ounces per person per day).

One of the lessons learned in the pilot study, the investigators noted, is that hospitals should involve clinicians early in the process of menu development. If you’re a clinician who is looking for one small, achievable Earth Day action that could make a big difference, consider showing this study to your hospital team. They (and the planet) may thank you.

–Sherry Boschert (@sherryboschert on Twitter)

Get Rrrrready to Rumble!

From the Second Annual Joint Surgical Advocacy Conference, Washington, DC

It’s increasingly obvious that a line in the sand is being drawn, and we’re not talking about one in the desert.  Primary care physicians and specialists appear to be headed for a smackdown, aided and abetted by a Congress that’s going to have to figure out how to fund health care reform and also avoid the statutory 21% cut in Medicare physician fees coming later this year.  

From Flickr Creative Commons user EdBob

Chest-beating was on vivid display at the Second Annual Joint Surgical Advocacy Conference earlier this week.  Eighteen specialty groups — from neurosurgeons to ophthalmologists to urologists to plastic surgeons to thoracic surgeons — banded together to hear rousing speeches from congressional allies and then to hop on buses to take their message directly to Capitol Hill.  Last year, there were only a handful of sponsors at the first annual conference. 

They’ve got reason to be worried.  From the Medicare Payment Assessment Commission to many Democratic congressional leaders, there has been a growing drumbeat of support for a redistribution of federal and private monies to prop up primary care, which is relatively underpaid — relative to specialty medicine, that is.

The specialists made it clear that they don’t want to open up their wallets to subsidize primary care. 

Rep. Roy Blunt (R-Mo.) stoked the specialists’ fire by asserting that no foreigner comes to America in search of primary care — rather, they’re looking for top-notch specialty services, he said.  He promised to protect specialists’ interests in his role as head of the Republican task force on health reform.

During question and answer sessions, more than one audience member chimed in that the primary care support should not come out of specialists’ hides.

A day later, specialists and primary care docs were going head to head during a House Energy & Commerce Health Subcommittee hearing.  The fun has just begun. 

— Alicia Ault