Bringing together teams across Europe and India with the support of the European Commission, the HPV-AHEAD project has conducted large-scale epidemiological studies and identified biomarkers that could provide early warning for human papillomavirus-induced head-and-neck cancer (HNC), potentially helping to save thousands of lives.

HNC is the sixth most common type of cancer globally, with one of the highest fatality rates. Around 550 000 cases affecting the mouth, throat and larynx are diagnosed worldwide each year, leading to around 300 000 deaths. Alcohol consumption, smoking, poor oral hygiene and genetic features are known to be key risks for HNC development, but in the last decade another factor has emerged: human papillomavirus (HPV).

More commonly associated with anogenital malignancies, especially anal cancer in men and women and cervical cancer in women, HPV is also now believed to be responsible for approximately 25 % of head-and-neck cancers, with one type, known as HPV16, accounting for up to 95 % of cases. This is important news for HNC patients as HPV positive tumours have a better prognosis and require different therapeutic regimens.

“While risk factors such as smoking have declined in Europe and the United States in recent years, in some regions HNC rates have steadily increased, suggesting a connection with HPV infection rates,” says Massimo Tommasino, the HPV-AHEAD coordinator at the Infections and Cancer Biology Group of the World Health Organisation’s International Agency for Research on Cancer (IARC).

In India, where cervical cancer caused by HPV is the most common cancer among women, the incidence of HNC is the highest in the world, accounting for up to 40 % of all cancers diagnosed in the country and a third of all cases of HNC worldwide.

Screening for cancer risk

Through epidemiological studies in Europe and India, the HPV-AHEAD researchers sought to establish the overall proportion and type distribution of HPV-positive HNC, define infection and cancer incidence trends and determine whether HPV infections interact with additional HNC risk factors.

By segregating teams at different laboratories using different assays on a large number of samples from HNC patients, the HPV-AHEAD researchers were able to define accurate and efficient procedures to determine the presence of HPV infection.

Within the project, a team coordinated by Paul Brennan at IARC back-tested the approach using blood samples taken from 500 000 people more than 20 years ago for an independent study, initially funded by the European Commission (EPIC – European Prospective Investigation into Cancer and Nutrition). Their findings showed that antibodies against specific viral proteins can be detected several years before the development of a malignant lesion. In contrast, in cervical cancer the same antibodies are considered very late markers.

“The immune response to HPV infection in the mouth and throat is very different to that in the cervix. The immune system is much more active in the oral cavity so antibodies are present much sooner after infection,” Tommasino explains. “This research should lead to new screening techniques for HPV-positive HNC, which would provide early warning for patients and contribute to the development of new therapies.”

Knowledge, assays and other technology developed in the project have been transferred to Indian partners and fully shared among all partners. Members of the consortium are planning to continue working together on refining the results and identifying additional biomarkers for HPV-associated HNC.

“We’re currently actively seeking funding to launch validation trials for new screening procedures in a clinical setting,” the coordinator says.