• 9/24/2007
  • Chicago, IL
  • Caroline Helwick
  • International Medicine World Report (www.imwr.com)

Infection with human papillomavirus (HPV) is emerging as a significant factor in head and neck squamous-cell carcinoma—with medical and perhaps social implications.

“HPV-related oropharynx carcinoma is beginning to constitute a significant portion of the oncologist’s practice in head and neck cancer,” said Marshall Posner, MD, medical director, Head and Neck Oncology Program, Dana-Farber Cancer Institute, Boston, who presented new study results at the annual meeting of the American Society of Clinical Oncology (ASCO). “HPV-related cancers are seen in as many as 25% of patients in community practice. At Dana-Farber, a referral cancer center, almost 50% of the oropharynx cancers we see are HPV-positive.”

HPV Infection Improves Prognosis

But the presence of HPV infection actually heralds a better prognosis in patients with these types of cancer, according to data from a new phase 2 prospective study conducted by the Eastern Cooperative Oncology Group (ECOG 2399).

This multicenter study confirmed retrospective, single-institution reports showing improved survival for patients with HPV-positive head and neck squamous-cell cancer compared with their HPV-negative counterparts. At ASCO, Carole Fakhry, MD, of the Johns Hopkins Medical Institutions, Baltimore, reported that a positive HPV infection status conferred a 79% lower risk of death in this population.

HPV status should now be considered a biomarker for prognosis in head and neck cancer, Dr Fakhry maintained. Moreover, these findings have implications for current treatment practices, as they may necessitate a reinterpretation of survival rates found in previous phase 2 trials to determine whether survival was the result of therapeutics or, in fact, the result of HPV status, she said.

New Study Results

The ECOG 2399 trial assessed organ preservation, disease-free survival; and patterns of failure with taxane-based induction chemotherapy followed by taxane-based concurrent chemoradiation in 96 patients with resectable stage III and IV larynx and oropharyngeal cancer. Investigators related the presence of HPV infection with prognostic factors, treatment response, and survival outcomes. They were particularly interested in HPV-16, the dominant viral isolate known to be responsible for a subset of head and neck cancers, along with HPV types 31, 33, and 35, the other isolates linked to these tumors.

HPV-positive tumors were detected in 40% of the patients; all cancers were oropharyngeal (Figure). Compared with HPV-negative patients, HPV-positive patients were more likely to:

– Have a better performance status
– Have a lower lifetime exposure to smoking
– Have less weight loss on presentation
– Be male
– Present with earlier-stage primary/ more-advanced nodal-stage tumors.

Of note, the patients who were HPV-positive had significantly higher response rates to induction and to chemoradiation therapy.

After more than 3 years of follow-up, the risk of disease progression was 72% lower, and the risk of death was 79% lower, in the HPV-positive patients as compared with the HPV-negative patients, Dr Fakhry said.

A Changing Epidemiology

Anil K. Chaturvedi, PhD, of the National Cancer Institute, Rockville, reported results of another study, which also investigated the relationship between HPV infection and head and neck squamous-cell carcinoma. Dr Chaturvedi said that HPV-related head and neck cancer has increased over the past 30 years, particularly among white men aged 40 to 59 years.

Using data from the Surveillance, Epidemiology, and End Results (SEER) registry for the period from 1973 to 2003, Dr Chaturvedi found that HPV-related tumors were being diagnosed at more advanced stages, and at a significantly younger age. The incidence of HPV-unrelated cancers, on the other hand, decreased in both men and women, especially in those over the age of 40. These trends became noticeable in the early 1990s.

Dr Chaturvedi proposes that the increasing incidence of HPV-associated tumors could be caused by changes in sexual behavior, and that the decreasing incidence of HPV-unrelated cancers could be the result of the decreasing prevalence of smoking.

In contrast to the once-traditional profile of the patient with head and neck cancer, up to 25% of the patients with this type of cancer are now:

– HPV-positive
– Young
– Nonsmoking
– Nondrinking.

Thus, today’s patients are often not diagnosed in a timely manner. But as evidence from the ECOG study shows, the life expectancy of the HPV-positive patients is actually higher, probably because they are, in general, healthier individuals, suggests Dr Posner.

Clinical Implications

“I believe this ‘epidemic’ of HPV disease is going to change the demographic and the urgency of treatment in this cancer,” Dr Posner maintains. “The fact that HPV-positive tumors have a better prognosis than oropharynx cancer caused by smoking is extremely important, because curing these patients will mean dealing with long-term sequelae in a young population living longer after treatment—living with scarring and fibrosis, as well as other complications from radiation, including a risk for second cancers,” he says.

He adds that in spite of the better prognosis for HPV-related tumors, aggressive treatment is critical. “We must remember that the improved prognosis for HPV-16 in the ECOG study was after a very intensive sequential therapy regimen that included aggressive induction chemotherapy and chemoradiotherapy. This does not mean we can lower the intensity of treatment for these patients and expect to maintain high cure rates. In our own practice, we have seen HPV-positive distant metastases in HPV-positive oropharynx patients treated with chemoradiotherapy alone.”

The prevalence of HPV-related oropharynx cancer also raises other issues, Dr Posner notes. “One, because this is a sexually transmitted disease, in which sexual practices [oral sex] increase risk, we must ask whether the patient’s significant other or sexual partners should be vaccinated or tested. Do they need surveillance? And what about children? It is possible that HPV is transmitted by saliva,” he asks. “These are questions for which we do not yet have the answers.”

KEY POINTS
– HPV-associated cancers are now seen in about 25% of patients in community practice and in almost 50% at cancer centers.
– Unlike the characteristics of the traditional patient, about 25% of current patients with head and neck cancer are HPV-positive, young, nonsmoking, and nondrinking.
– In a new study, a positive HPV infection status conferred a 72% lower risk of disease progression and a 79% lower risk of death.