Beyond Pack-Years: Assessing & Treating HPV+ Oropharynx Cancer

Incorporation of longer terms of smoke exposure and other relevant parameters into disease classification may improve overall risk-stratification paradigms and strengthen clinical trial designs for patients with human papillomavirus-positive (HPV+) oropharynx cancer, according to a new study.

“Smokers are known to have worse outcomes and shorter survival than nonsmokers in cases of HPV-positive oropharynx cancer,” says Shlomo Koyfman, MD, senior author on the study and a radiation oncologist at Cleveland Clinic. “Our analysis showed that 20 pack-years of smoke exposure is a more reliable indicator of high-risk disease than the typical 10-year cutoff affords.”

Additional relevant variables include Charlson comorbidity score and primary tumor size, according to the study, “Impact of smoking on outcomes in HPV+ oropharynx cancer: It′s more than pack-years,” which is being presented this week at the ASTRO conference in San Diego.

Finding an overlooked indicator

Suspicious that existing risk-stratification tools and clinical trial designs underappreciate the effect that higher pack-years and other indicators can have, Dr. Koyfman and the team set out to examine the impact of smoking status on clinical outcomes in HPV+ squamous-cell carcinoma of the oropharynx.

They found that active smoking at the time of diagnosis and/or continued smoking through treatment represented the most powerful predictor of both progression-free (PFS) and overall survival (OS).

“We weren’t surprised by this,” says Dr. Koyfman. “It’s pretty straightforward.”

The second most-powerful predictor was exposure to 20 pack-years of smoke or more.

“What did surprise us is that most clinical trials and risk-stratification schemes cutoff their assessments at 10 pack-years when both 20 pack-years and active smoking represent more meaningful indicators,” he continues.

Broad range of patients and tumor types

The study involved a retrospective statistical analysis of 484 patients with HPV+ SCC of the oropharynx between 2001 and 2005 whose cancers ranged from stage I-IVB. Participants included 94 active smokers (19 percent), 226 former smokers (47 percent) and 164 never smokers (34 percent).

About half of the active and former smokers (247 patients, 51 percent) had at least 10 pack-years of smoke exposure, and about one-third of them (179 patients, 37 percent) had at least 20 pack-years exposure.

Analyses performed on the cohort included univariate, multivariate, Charlson scoring of comorbidities and primary tumor sizing.

A detailed analysis

On univariate analysis, all smoking parameters (any smoker, > 10 pack-years, > 20 pack-years and active smokers) were significantly associated with inferior OS. Multivariate analysis showed active smoking was the smoking-related variable most strongly associated with inferior OS and PFS (HR = 3.4 and HR 2.2, respective univariate and multivariate analysis).

Other parameters significantly associated with inferior OS and PFS included higher Charlson scores (HR = 4.2 and HR = 4.0, univariate and multivariate analysis) and T4 primary tumor size (HR = 2.9 and HR = 3.0).

When analyzed by pack-years in a separate multivariate analysis, smoking 20 or more pack-years was significantly associated with worse OS and PFS (HR = 3.1 and HR = 1.6), in addition to higher Charlson scores and T4 disease.

“We conclude that future studies should validate these findings and potentially replace the 10 pack-year cutoff with either a 20 pack-year cutoff or active smoking cutoff,” says Dr. Koyfman.