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HPV status in head and neck cancer may affect treatment decisions

For the Summer feature, we're highlighting head and neck cancer that is associated with HPV, the human papillomavirus. Although this virus first gained public awareness as a cause of cervical cancer, it's increasingly linked to other cancers, such as vaginal, penile and anal.

In the past, alcohol and tobacco use was considered the leading cause of head and neck cancer. Recently, however, it was discovered that most head and neck cancers are linked to HPV. And what we're finding is that these HPV-associated head and neck cancers respond better to chemotherapy than those linked to tobacco and alcohol. Read: Men may be at greater risk than women of developing HPV-related cancer.

Once this was discovered, researchers began to question whether HPV-associated head and neck cancers could be treated differently, maybe with a different regimen or even less treatment. In the head and neck session today at ASCO, researchers looked at whether HPV status affected overall survival and progression-free survival when the EGFR-targeted agent Vectibix (panitumumab) was added to standard chemotherapy.

SPECTRUM was a phase 3 trial published a few years ago testing Vectibix (panitumumab) in first-line recurrent or metastatic squamous cell head and neck cancer. More than 650 patients were randomized to received cisplatin and 5-FU with or without Vectibix every three weeks. Researchers found that the addition of Vectibix did not statistically improve overall survival. However, they have continued to mine the data from the trial for further information.

Researchers believe HPV-positive head and neck cancers are clinically and biologically distinct from HPV-negative tumors, but the role of HPV status in predicting response to EGFR inhibitors such as Vectibix is still unknown. What is known is that HPV damages DNA indirectly, while chemicals in tobacco and alchohol damage DNA directly. This difference may account for why HPV-positive tumors are more responsive to treatment.

During the SPECTRUM trial, 67 percent of patients provided tumor samples and HPV status was examined. Of the HPV-positive patients, about two-thirds were former smokers of 10-pack years or more. (A pack-year is equal to about a pack of cigarettes a day for one year.) Still, their overall survival was not much different.In HPV-positive cancers, survival was 11 months and 12.6 months in favor of chemotherapy alone. In HPV-negative patients, the Vectibix arm was favored, with median survival reaching 11.7 months compared with 8.6 months with chemotherapy alone. The progression-free survival data followed the same trend, with HPV-positive patients faring better with chemotherapy alone and HPV-negative favoring the Vectibix arm.

The search for additional tumor biomarkers and covariates for response to Vectibix in these patient populations is ongoing, researchers noted. What is apparent is that HPV-associated tumors may need to be treated differently than HPV-negative tumors – and that may be with less treatment.

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