TORONTO—Patients with head and neck squamous cell carcinoma (HNSCC) who have no history of tobacco or significant alcohol use appear to be more likely to present with earlier disease and smaller initial T-stage, but have worse than expected outcomes.
These were the findings from a retrospective chart review of 101 patients with head and neck cancer, which included a subset of patients who had no smoking or drinking history. Details of the study were presented here at the recent meeting of the Eastern Section of the Triological Society by Miriam O’Leary, MD, a resident in the Department of Otolaryngology at the Boston University School of Medicine (Mass.).
“As we know, alcohol and tobacco use are well established risks for the development of head and neck squamous cell carcinoma. However, there is a growing body of data on cancer patients who do not have these typical risk factors,” she said. Studies in the medical literature report that between 10% and 25% of head and neck cancer patients do not have a history of tobacco smoking or drinking.
“The big thing that we could pull out of the study was that 5 of the 17 people had none of the examined comorbidities. We couldn’t pull out any data that supported any significant exposure to any of those things.” – —Anand Devaiah, MD
This brings up the question of what other factors or comorbidities could contribute to the risk these patients have for developing the cancers or their outcomes.
A retrospective chart review was done of patients with new head and neck cancer diagnoses who presented between the years 2001 and 2004, and for whom follow-up data were available. Tumor sites included were the oral cavity, orolarynx, and hypopharynx—sites that are typically associated with tobacco and alcohol use.
For the purposes of the study, significant tobacco use was defined as any history of regular tobacco smoking, and drinking was more than one alcoholic beverage a day. Anything less was considered non-use, and patients were included in the study.
During the study period a total of 101 patients presented with head and neck cancer, and of these a subset of 17 had no significant history of tobacco or alcohol used. “This proportion of approximately 17% correlates well with the published range of 10% to 25%,” Dr. O’Leary said.
The patients in the subset were an average age of 59 years (ranging from 21 to 80); ten were female, and over half the patients had early-stage or T1 tumors. More than half the tumors were in the oral cavity, while the rest were distributed between the oropharynx and larynx.
The study period ended in January 2005, and at that point seven of the patients had no evidence of disease after treatment, five were alive with disease, two had died from the cancer, and three were lost to follow-up.
“Of the cancer patients that we identified without the traditional risk factors for head and neck squamous cell carcinoma, the majority presented with early stage disease, yet half of them recurred or perished from their disease during our study period,” Dr. O’Leary said.
When compared to the patients with traditional risk factors in the medical literature, the non-drinking, non-smoking cohort faired worse. “They appear to have a worse prognosis, which is worrisome. Interestingly, most of these patients had more than one comorbidity,” she said.
The Role of Comorbidities
In the study, researchers investigated various comorbidities or factors that could have influenced cancer risk or outcome. In an interview with ENToday, Anand Devaiah, MD, Assistant Professor of Otolaryngology and Neurological Surgery at the University of Boston School of Medicine and the study’s lead author, said that an extensive list of additional factors were taken into account.
Patient histories were examined for a total of 15 comorbidities, 15 social exposures (such as working with toxins at work), use of immunosuppressive classes of medication, family history, and personal history of cancer.
Among the 17, three patients had diabetes, four had poor dental hygiene, four reported rare alcohol use, and two had reflux. However, the numbers are small and lack statistical power to determine causality, Dr. Devaiah said.
In the end, “we can’t conclude any one factor is causative—but this doesn’t mean it’s not a risk factor.” He noted that the patients with diabetes each had at least one other comorbidity.
“The big thing that we could pull out of the study was that 5 of the 17 people had none of the examined comorbidities. We couldn’t pull out any data that supported any significant exposure to any of those things,” Dr. Devaiah said.
Of the five who had no other apparent risk factors, two died from the cancer and one is being treated for recurrence of the disease. Only two are still alive with no evidence of the disease recurring.
Normally, patients who present with early stage disease have a significantly better cure rate. “But our patients, or this subset, had a worse outcome. The tumours seemed to be more aggressive. We certainly didn’t skimp on their treatment,” he said.
Genetics could be playing a role in the subset of patients who neither smoke nor drink, and the researchers plan to pursue studies in this direction. In the meantime, otolaryngologists should still encourage patients to quite smoking, reduce drinking, and make healthy lifestyle choices, he said.
As an aside, Dr. Devaiah also pointed out that while the medical community knows that “there’s no therapeutic benefit to tobacco use at all,” there is still some uncertainty about the protective effects of moderate alcohol use. While a glass a day of wine has been indicated as being protective for heart disease, there could be increased risks when it comes to other health conditions. “We’re not sure what is really safe for alcohol consumption,” Dr. Devaiah said.
In fact, with smoking rates going down as reported by the American Cancer Society, there is now some suspicion that alcohol may play a larger role than previously believed. Some European data suggest there maybe an increased risk of head and neck cancer with increased alcohol use alone, Dr. Devaiah said.
Good Study, Questions Remain
Gady Har-El, MD, Professor of Otolaryngology and Neurosurgery at SUNY Health Science Center in Brooklyn, NY, who was not part of the Boston study group, said that this sort of study is important in trying to figure out what is going on with patients who lack traditional risk factors such as smoking and drinking.
“For the last 20 years we’ve been seeing more and more of them. They are young and we’re not sure exactly what’s gong on. This study was nice and done in such a way that it was trying to find some comorbidity—some other issue that may contribute to the occurrence of cancer in this subset of patients,” he said.
Another factor worth considering is whether human papilloma virus (HPV) plays a role in increasing the risk in this subset of patients. “There are a few studies now, both in Europe and the United States, that raise the question of transmission of oral papilloma virus in an oro-genital way. They talk about the indirect relation of human papilloma virus in oral cavity cancer and the uterine cervix, which is an interesting thing,” Dr. Har-El said.
If studies show there is such a connection, then the HPV vaccine could be useful for people at risk.
©2006 The Triological Society