Patients with discordant p16 or HPV DNA or RNA tests are less likely to survive than those positive for both.
Experts are calling for patients with head and neck cancer to get two different types of HPV test, after results show discordant and negative results on both are linked to significantly worse outcomes.
The findings clear up a long-standing puzzle around why some HPV-positive patients were much more likely to survive than others.
Researchers analysed health data from almost 8000 oropharyngeal cancer patients across Europe, the UK and Canada and found that patients whose cancers were HPV-negative were significantly more likely to die over the five-year follow up, followed by those with discordant results.
While HPV-related oropharyngeal cancers have ballooned since 2000, the cost of HPV DNA and RNA testing is high, and testing can be difficult to implement. As a result, immunohistochemical tests for a protein, known as p16, are commonly used as a surrogate.
But around one in five patients who test positive for p16 don’t test positive for HPV DNA or RNA, and until now it has been unclear what their prognosis looks like.
Professor Hisham Mehanna, professor of head and neck surgery at the University of Birmingham, UK, and colleagues found that almost half of the participants in this study tested negative to p16 and HPV, and 44% tested positive for both. Around 4% were negative for p16 but positive on the HPV test, and 5% were p16-positive, HPV-negative.
Overall survival was an average of 15 years for patients who tested positive on both, around five and a half years for patients who were p16-negative and HPV-positive and six years for patients who were p16-positive but HPV-negative. Average overall survival was only three and a half years for patients who tested negative on both.
At the five-year mark, 81% of patients who tested positive on both survived, 55% of patients who were p16-positive but HPV-negative, 53% of patients who were p16-negative but HPV-positive and 40% of patients who were negative on both.
“Through an international collaboration we have been able to answer a question that has perplexed the head and neck cancer community for over two decades,” Professor Mehanna said in a statement.
“What is remarkable is that patients with HPV head and neck cancer respond much better to current therapies than patients who are not HPV-related. As a result, we are trying to look for less toxic treatments for these patients to reduce the burden of toxicity. For patients who are HPV negative, we are doing clinical trials to increase the intensity of treatment – to try to improve outcomes.
“Therefore, testing for HPV in head and neck cancer patients has become a real priority and this new research has solved the conundrum puzzling the international community about why some patients respond much better to treatment than others.”
The authors also found that patients who smoked and were p16-positive had worse survival rates than those who tested positive on both tests.
The authors called for routine HPV DNA and RNA testing alongside p16, saying both were “recommended in the clinical setting for more accurate counselling on prognosis, and in future circumstances in which treatment de-escalation or intensification are being considered.”