Author: Charles Bankhead, Staff Writer, MedPage Today

Higher pretreatment levels of cytotoxic T lymphocytes may help identify patients with head and neck cancer who have a favorable prognosis and require less aggressive treatment, according to a study reported here.

A higher proportion of CD8 cells predicted improved survival in patients with oropharyngeal cancer associated with human papillomavirus-16 (HPV-16), investigators reported at the American Head and Neck Society.

The finding supports the hypothesis that a patient’s adaptive immunity may play a role in the favorable prognosis of HPV 16-related head and neck cancer.

“We had hypothesized that a better immune status might be responsible for the better survival,” Gregory T. Wolf, MD, of the University of Michigan in Ann Arbor, said in an interview. “The next step will be find out what the function of these cells might be and whether they are really contributing to the control of the cancer or to good response to therapy.”

The results also support the feasibility of using a biologic marker to identify patients with head and neck cancer that can be treated less aggressively, sparing patients from some of the treatment-related morbidity, Wolf added.

Confirming the association between CD8 cells and survival is the latest step in a scientific journey that began about 15 years ago, when researchers and clinicians began to notice that a subgroup of patients with oropharyngeal cancer had a more favorable prognosis than would have been expected. Many of the patients tested positive for HPV, specifically HPV-16.

Wolf and colleagues previously found that pretreatment levels of CD8 and CD4 (helper T cells) were associated with a favorable prognosis in patients with head and neck squamous carcinoma. The current study was designed to define the association more specifically, particularly the contributions of a patient’s own adaptive immunity.

The study involved 66 patients with stage III-IV previously untreated head and neck cancer. Pretreatment peripheral blood lymphocyte subpopulations were assessed in 47 of the patients. Subset analysis included CD3, CD4, CD8, natural-killer, and B cells, as well as total white blood cell (WBC) count.

All patients received the same therapy: a single course of neoadjuvant chemotherapy, followed by either surgery or concurrent chemoradiation.

After a median follow-up of 6.6 years, four-year disease-specific survival was 76%.

Statistically significant predictors of improved survival were a higher percent CD8 level (P=0.043), lower expression of epidermal growth factor receptor (P=0.002), and HPV status (P=0.017).

HPV-positive patients had significantly higher levels of CD8 cells (P=0.038), a significantly lower CD4/CD8 ratio (P=0.021), and a lower total WBC (P=0.016).

A higher proportion of CD8 cells predicted an increased likelihood of response to induction chemotherapy (P=0.022) and complete tumor response after chemoradiation (P=0.045). Local failure was associated with low CD8 levels (P=0.035).

The mean WBC was higher and hemoglobin lower in smokers versus former smokers and nonsmokers, but lymphocyte subsets did not differ between smokers and nonsmokers.

The field of oropharyngeal cancer has changed dramatically in a relatively short period of time, said Wolf. As recently as the 1990s, about 25% to 30% of oropharyngeal cancers were HPV positive. Current estimates are in the range of 80% to 90%.

HPV-related oropharyngeal cancer affects men and women with roughly equal frequency. Most patients do not smoke, and most are not heavy drinkers, factors closely associated with other types of head and neck cancer.

As in HPV-associated cervical cancer, sexual activity is strongly associated with HPV-positive oropharyngeal cancer, Wolf continued.

Most specialists in oropharyngeal cancer now refer to the HPV-related cancer as a sexually transmitted disease, he said. Clinical trials are assessing whether vaccination against HPV can prevent the cancer in men as well as women.

“We’re in a paradigm-shifting kind of moment in head and neck cancer,” said Wolf. “Up to now, I think clinicians had been reluctant to accept a biologic marker, if you will, to help select treatment. The improved prognosis associated with HPV-16 is so consistent and so overwhelming that it will change the way clinicians approach these cancers.”

1. Wolf disclosed a relationship with IRX Therapeutics.
2. Source: American Head and Neck Society
3. Reference: Wansom D, et al “Cellular immunity correlates with human papillomavirus-16 (HPV-16) status and outcome in patients with advanced oropharyhngeal cancer” AHNS 2010; Abstract S043.

Print Friendly, PDF & Email