National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
October 4, 2011 • Volume 8 / Number 19

Cancer Research Highlights

Rising Oropharyngeal Cancer Rates Linked to HPV Infection

A new study provides evidence that human papillomavirus (HPV) infection may be responsible for the rise in incidence of oropharyngeal squamous cell carcinoma (OPSCC), a type of head and neck cancer. The research suggests that if these trends continue, by 2020 HPV-positive OPSCC will likely surpass cervical cancer as the most common HPV-associated cancer in the United States. The findings were published online October 3 in the Journal of Clinical Oncology.

Originally thought to be a single disease, OPSCC is now recognized as two distinct tumor types: HPV-positive and HPV-negative. HPV-negative tumors are associated with tobacco and alcohol use, older age at diagnosis, and a poorer prognosis, whereas HPV-positive cancers have risk factors related to sexual behavior, are diagnosed in younger people, and tend to have better survival rates.

A previous study by the same authors showed that OPSCC diagnoses had been increasing since the early 1970s, even as rates of other oral cancers dropped. “We expected that the oral cancers would decline in incidence,” explained lead author Dr. Anil Chaturvedi of NCI’s Division of Cancer Epidemiology and Genetics, “because cigarette smoking, which is a strong risk factor for these cancers, has declined in the United States. The increasing incidence of oropharyngeal cancers during the same time suggested that there could be another risk factor. We hypothesized that HPV infection could be leading to the rise in oropharyngeal cancer incidence.”

To evaluate the prevalence of HPV in OPSCC tumors over time, the researchers used tissue samples from three registries in the Surveillance, Epidemiology, and End Results Residual Tissue Repository Program. They used several molecular techniques to detect HPV DNA, viral load, and mRNA in 271 OPSCC tumor samples collected between 1984 and 2004.

The prevalence of HPV in tumor samples (as assessed by HPV DNA) surged from 16.3 percent in the second half of the 1980s to 72.7 percent during the early 2000s, the researchers found. “These increases may reflect changes in sexual behavior, including increases in oral sex,” said senior author Dr. Maura Gillison of the Ohio State University in a news release.

The researchers also discovered that the incidence of HPV-positive OPSCC in the population more than doubled between the late 1980s and early 2000s, while that of HPV-negative cancers fell 50 percent.

Patients with HPV-positive OPSCC were more likely than patients with HPV-negative OPSCC to be younger and male, and they had better long-term survival rates (median survival of 131 months, versus 20 months for HPV-negative cancers), especially if they were treated with radiation therapy. But “not everyone with HPV-associated cancers is cured,” said Dr. Arlene Forastiere of the Johns Hopkins University, “and we are seeking to understand the molecular genetics of that [patient] subset.”

These findings are not likely to result in immediate treatment changes for OPSCC patients, but they can enroll in clinical trials specifically studying HPV-positive OPSCC, noted Dr. Forastiere.

Since the majority of the HPV-positive tumors contained HPV type 16 DNA, vaccination against this type prior to exposure—in men and women—also may be beneficial, as no screening techniques currently exist. But studies are needed to evaluate the efficacy and cost-effectiveness of vaccination, Dr. Chaturvedi added.

Hospitalization Following Prostate Biopsy Common in Older Men

Men 65 years of age or older who underwent a prostate biopsy were more likely to be hospitalized for a serious complication within 30 days than men who did not have the procedure, according to a new study. The rate of infectious complications, in particular, has risen substantially in recent years, researchers from the Johns Hopkins University School of Medicine reported online September 22 in the Journal of Urology.

To conduct the study, Dr. Edward Schaeffer and his colleagues analyzed clinical records from 1991 through 2007 for nearly 17,500 Medicare beneficiaries who had had a prostate biopsy and approximately 135,000 male Medicare beneficiaries who had not had a prostate biopsy. The data came from NCI’s Surveillance, Epidemiology, and End Results database.

Overall, 6.9 percent of men who had a biopsy were hospitalized within 30 days of their first biopsy. By comparison, only 2.9 percent of the men in the control group were hospitalized within 30 days of a randomly selected date. Men who had had a prostate biopsy had a more than 2.5-fold increased risk of hospitalization for a serious bacterial infection and a more than eightfold increased risk of a complication unrelated to a bacterial infection.

Among men who had a biopsy, rates of hospitalization for reasons unrelated to infection remained relatively stable during the study period, Dr. Schaeffer noted, but rates of hospitalization for infection-related complications rose sharply from 2000 to 2007. The finding seems to confirm what urologists around the country have reported anecdotally: A growing number of men are developing antibiotic-resistant infections following a prostate biopsy.

“Two decades ago we didn’t have problems with resistant organisms,” Dr. Schaeffer said. The available evidence suggests that it may be a growing problem, he continued, “and we have to do a better job of controlling it.”

Men about to undergo a prostate biopsy typically receive antibiotics to prevent infections. The Johns Hopkins research team is working with researchers at the Northwestern University Feinberg School of Medicine to investigate whether pre-biopsy testing for antibiotic-resistant bacterial strains can reduce infection rates. They have also launched a study of infection rates in men with low-risk prostate cancer enrolled in the active surveillance program at Johns Hopkins, who undergo periodic prostate biopsies.

More than one million Medicare beneficiaries undergo prostate biopsies annually, in most cases as a result of screening for prostate cancer, the study authors noted. Had similar findings been seen in a randomized clinical trial, they added, 1 of every 24 patients who underwent a prostate biopsy would be hospitalized for a complication within 30 days.

“Although prostate biopsy is often considered a benign procedure,” the researchers wrote, “these findings highlight the importance of individualized assessment of the risk-to-benefit ratio of this potentially risky procedure.” Clinicians should discuss the potential for complications with patients considering prostate biopsy, they concluded.

Study Examines Sex Differences in Screening Colonoscopy Findings

A large study in Austria has shown that the prevalence of abnormal growths detected in screening colonoscopies is higher in men than in women at all ages. The study results, reported September 28 in JAMA, suggest that the optimal age for an initial screening colonoscopy may differ for men and women.

In many countries, including the United States and Austria, guidelines recommend screening for colorectal cancer (CRC) starting at age 50 for men and women of average risk. Colonoscopy is used to find and remove precancerous growths known as polyps or adenomas, especially advanced adenomas (AAs). Colonoscopy also can detect CRC at an earlier stage, when it is generally more treatable.

“This study is important…but it’s not a reason to change screening recommendations in the United States. It’s one report, and the implications for people in the United States aren’t clear,” said Dr. Stephen Taplin, a cancer screening expert and chief of the Process of Care Research Branch in NCI’s Division of Cancer Control and Population Sciences

The study, led by Dr. Monika Ferlitsch of the Medical University of Vienna, analyzed findings from 44,350 participants in a national screening colonoscopy program from 2007 to 2010. Women made up 51 percent of the study population, and the median ages were 60.7 years for women and 60.6 years for men.

Dr. Ferlitsch and her colleagues found that the rates of adenomas, AAs, and CRC detected by colonoscopy were higher in men than in women at all ages, with men having twice the risk of CRC detected by colonoscopy as women. The prevalence of AAs detected was similar between men 45 to 49 years of age and women 55 to 59 years of age. The average number of patients who had to be screened to detect adenomas, AAs, or CRC was significantly higher in women than men.

“There is interest in the wider community of people working on disease screening to think about individualizing recommendations based on more than age,” Dr. Taplin noted. “This study is beginning to push the envelope of research” in that area, he said.

However, Dr. Taplin added, the study findings “need to be replicated in other populations, including those that are more diverse and have different dietary habits than in Austria.” He noted that U.S. SEER cancer statistics show CRC rates only one-third higher in men than women.

Dr. Taplin added that NCI is launching a multicenter research program called PROSPR that will include studies of the benefits and risks of cancer screening in people with different risk profiles in community practice settings in the United States.

Delivering Chemotherapy to the Liver May Benefit Patients with Metastatic Melanoma

For patients with melanoma of the eye (ocular or uveal melanoma) that has spread to the liver, a new technique may delay the progression of the disease better than current treatments, new research suggests. The technique, called percutaneous hepatic perfusion, delivers chemotherapy directly to the liver, sparing other parts of the body from the drug’s effects.

Ocular melanoma frequently spreads to the liver, and because there are no effective treatments, most patients die within several months. 

“This is the first treatment to show a clinical benefit in patients with liver metastases from ocular melanoma,” said Dr. James Pingpank of the University of Pittsburgh Cancer Institute in a news release. He presented results from a study testing the approach—sometimes called regional chemotherapy—last week at the European Multidisciplinary Cancer Congress in Stockholm, Sweden.

In the phase III clinical trial, 93 patients were randomly assigned to receive regional chemotherapy or the best alternative therapy, as chosen by the investigator. The median time before disease progressed in the liver was 8.1 months among those who received regional chemotherapy, compared with 1.6 months for those in the control group.

The study, which began at NCI and was expanded to nine other U.S. medical centers, also showed a benefit in median overall progression-free survival: 6.1 months in the regional chemotherapy group versus 1.6 months in the control group. Most patients retained 80 percent or more of their daily functional status and returned to full performance once therapy was completed, said Dr. Pingpank.

Patients who initially received the best alternative care were allowed to cross over and receive regional chemotherapy if the disease continued to progress. “These patients were able to achieve a benefit from regional chemotherapy even after their earlier treatment,” said Dr. Marybeth Hughes of NCI’s Center for Cancer Research, who co-led the trial.

To deliver the drug, melphalan, doctors use an intra-arterial catheter, inserted through the skin to deliver drugs to the liver, capture the flow of blood from the liver, and then remove the drugs from the blood before it returns to the rest of the body. The technique avoids the complications of major surgery and can be repeated if necessary.

“We see this as a frontline therapy for patients with this disease,” said Dr. Pingpank in the news release. He noted, however, that applying a regional therapy to patients with metastatic disease can be controversial, especially if there is a high risk for metastases elsewhere in the body.

A similar approach could potentially be used for other cancers that have spread to the liver. At the meeting, Dr. Pingpank and his colleagues reported positive results from a phase II study of percutaneous hepatic perfusion for patients with metastatic neuroendocrine tumors.

The device used to deliver and filter the melphalan has been approved in Europe for use in all malignant liver tumors, whereas approval is pending in the United States for melanoma only, the researchers said.

Smoking Cessation Drug Proves Effective in Single-Center Trial

In a single-center randomized controlled trial, the smoking cessation drug cytisine was more effective than a placebo at helping participants abstain from smoking. Results from the trial, conducted at the Maria Sklodowska-Curie Memorial Cancer Center in Warsaw, Poland, appeared in the September 29 issue of the New England Journal of Medicine.

Cytisine binds to the alpha-4 beta-2 nicotinic acetylcholine receptor, which has been implicated in nicotine dependence and is the primary target for the smoking cessation drug varenicline. Cytisine has been available for more than 40 years as a smoking cessation aid in some eastern European countries, although results from animal studies have suggested that cytisine might have limited efficacy in humans.

The research team randomly assigned 740 participants to receive cytisine or a placebo for 25 days. All study participants received a minimal amount of counseling. Twelve months after the end of treatment, 31 participants in the cytisine group and 9 in the placebo group remained smoke-free, an abstinence rate of 8.4 percent versus 2.4 percent. Smoking abstinence was verified by measuring the carbon monoxide concentration in exhaled breath.

Cytisine resulted in more gastrointestinal adverse events than did placebo, but rates of other adverse events and death were similar in the two groups. The rates of discontinuation or dose reduction were also similar with cytisine and placebo.

“Combining cytisine with more intensive behavioral support may result in higher absolute quit rates,” wrote the authors, “and it is possible that efficacy could be improved by a longer regimen.” They also noted that the lower cost of cytisine as compared with that of other smoking-cessation drugs “may make it an attractive treatment option for smokers in low-income and middle-income countries.”

Dr. Michele Bloch, acting branch chief of NCI’s Tobacco Control Research Branch, noted, “The combination of cytisine with behavioral strategies is promising and worthy of further investigation.”


Also in the Journals: Zoledronic Acid May Benefit Postmenopausal Women with Breast Cancer

A planned subset analysis of a phase III trial showed that adding zoledronic acid, a bisphosphonate, to standard adjuvant therapy for stage II or III breast cancer may improve outcomes in postmenopausal women. Overall, among the entire trial population of 3,360 women, the addition of zoledronic acid did not improve outcomes. 

However, among a subset of women who had undergone menopause 5 or more years before study entry, the 5-year overall survival rate was 85 percent for those who received zoledronic acid, compared with 79 percent for those treated with standard adjuvant therapy alone.

These findings from the AZURE trial were published online September 25 in the New England Journal of Medicine and presented the same day at the 2011 European Multidisciplinary Cancer Congress. In the full study population, there were 17 confirmed and 9 suspected cases of osteonecrosis of the jaw in the zoledronic acid group and none in the control group.

The benefit in overall survival among postmenopausal women “is a small but significant increase,” said principal investigator Dr. Robert Coleman in a news release. The finding is not conclusive on its own but “in the context of other studies and additional data anticipated later in the year,” he believes it may change practice.