February 17, 2010 – It is well established that patients with squamous cell carcinoma of the oropharynx that tests positive for human papillomavirus (HPV) have a more favorable outcome and are more likely to be nonsmokers than patients who are HPV-negative.
As a consequence, clinicians are now generally advised to test all of these kinds of head and neck cancers for HPV status and guide treatment and patient counseling accordingly, as reported by Medscape Oncology.
But what about patients with HPV-positive tumors who also have to have a history of tobacco use?
Their prognosis is not likely to be as good as their fellow HPV-positive patients who have never smoked, according to a new study published in the February 15 issue of Clinical Cancer Research.
HPV-positive current tobacco users were over 5 times more likely to develop a recurrence than HPV-positive never users (hazard ratio, 5.2; 95% confidence interval, 1.1 - 24.4; P = .038), according to investigators at the University of Michigan in Ann Arbor.
The results of the study have implications for clinical practice, suggested the study's lead author, Thomas Carey, PhD, professor of otolaryngology and pharmacology, and codirector of the Head and Neck Oncology Program at the University of Michigan Comprehensive Cancer Center.
"What's currently being discussed nationally is whether or not we can safely reduce treatment in HPV-positive patients to reduce toxicity," said Dr. Carey.
He explained that "high cure rates" and "pretty toxic" chemotherapy and radiation treatment regimens in these HPV-positive patients have prompted wide interest in reducing treatment-related morbidity.
However, the new study results serve as a reminder that clinicians "should not change the way they treat patients until clinical trials prove it makes sense," he told Medscape Oncology.
Furthermore, Dr. Carey said in a press statement that if clinicians "decide to reduce the intensity of treatment, our study shows we will want to take tobacco use into account."
The new study's findings are not entirely novel, note Dr. Carey and his coauthors.
One other study found that nonsmoking patients with HPV-positive tonsillar squamous cell carcinoma have a better disease-specific survival rate than their smoking counterparts (Int J Cancer. 2008;122:2656-2664). However, several other reports indicate no effect of the interaction between smoking and HPV on survival. These counterintuitive findings might be related to how patients' smoking histories were categorized in the studies, suggested Dr. Carey.
Smokers Have HPV-Positive Tumors Too
Patients with squamous cell carcinoma of the oropharynx that test positive for HPV are "much more likely to be nonsmokers" in "broad data" related to these head and neck cancers, said Dr. Carey.
However, when Dr. Carey and his colleagues prospectively looked at 124 patients treated at the University of Michigan between 1999 and 2007 with stage III or IV squamous cell carcinoma of the oropharynx, they discovered a considerable amount of tobacco use among the HPV-positive patients.
Of the 124 patients with squamous cell carcinoma of the oropharynx in the study, 22 were HPV-negative. Not surprisingly, all 22 were tobacco users. The other 102 patients had HPV-positive tumors. Somewhat surprisingly, more than two thirds (68%) of these HPV-positive patients were also tobacco users (cigarettes, cigars, pipes, or chewing tobacco), currently and formerly.
The tobacco users consisted of 23 who were current users and 46 who were former users.
All of the patients in the study were enrolled in 1 of 2 consecutive treatment protocols.
Forty-one patients were treated with induction chemotherapy (cisplatin and 5-fluorouracil) followed by concomitant cisplatin and full-course radiation (70 Gy) or surgical resection and full-course radiation for nonresponders to induction chemotherapy; 83 were treated with concomitant carboplatin, docetaxel, and intensity-modulated radiation therapy (70 Gy).
For the sake of analysis, the 2 cohorts were analyzed together in the study. The 124 total patients (21 females and 103 males) from both cohorts were similar in age, race, primary tumor site, clinical stage, tumor classification, and nodal classification, report the authors.
The median follow-up time was 76 months and 36 months for the 2 different treatment groups, respectively. The primary end points were risk for disease recurrence and time to recurrence.
Thirty-five percent of HPV-positive ever users of tobacco had a recurrence, compared with only 6% of HPV-positive never users and 50% of HPV-negative patients, report the authors.
As noted above, all HPV-negative patients were tobacco users; they had significantly shorter times to recurrence (P = .002), and had lower disease-specific survival (P = .004) and overall survival (P < .001) than HPV-positive patients, write the authors.
Compared with HPV-positive never-users of tobacco, those with a tobacco history showed a trend toward reduced disease-specific survival (P = .064) but not overall survival (P = .221).
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