Rise in Oropharyngeal Cancer Incidence in the UK Not Solely Driven by HPV

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The rise in the incidence of oropharyngeal squamous cell carcinoma in the United Kingdom from 2002 to 2011 was not solely attributable to a rise in the incidence of human papillomavirus (HPV)-positive disease, according to a study published in Cancer Research,1 which reported that the proportion of HPV-positive and HPV-negative cases remained the same throughout that period.

Terry M. Jones, MD

Terry M. Jones, MD

“Incidence of oropharyngeal squamous cell carcinoma has been increasing throughout the developed world since the mid-to-late 1990s,” said Terry M. Jones, MD, Professor of Head and Neck Surgery in the Department of Molecular and Clinical Cancer Medicine at the University of Liverpool, United Kingdom.

HPV-Negative Cancer Incidence Also Rises in UK

“Several studies suggest that this rise was driven by increasing incidence of HPV-positive disease, but we wanted to determine whether this was the case across all four countries of the United Kingdom [England, Ireland, Scotland, and Wales].

“We were surprised to find that while the overall incidence of oropharyngeal squamous cell carcinoma in the United Kingdom rose year on year as anticipated, the proportion attributable to HPV remained static, meaning that not only is HPV-positive oropharyngeal squamous cell carcinoma increasing in incidence, but that HPV-negative oropharyngeal squamous cell carcinoma disease incidence is rising in parallel,” said Dr. Jones.

“This is different to trends reported elsewhere in the developed world,” he pointed out. As a result, Dr. Jones said that this illustrates that the causes underlying the rise in oropharyngeal squamous cell carcinoma incidence cannot be generalized between populations and need to be analyzed in a population-specific manner. The National Cancer Institute states that in the United States, estimates of the incidence of HPV-positive oropharyngeal cancers increased by 225% from 1988 to 2004, whereas the incidence of HPV-negative cancers declined by 5%.2

Dr. Jones explained that because there are multiple factors that cause oropharyngeal squamous cell carcinoma, including HPV infection, smoking, and alcohol consumption, these data have direct and immediate relevance to public health officials whose responsibility it is to develop disease prevention strategies.

Archival Tumor Tissue Analyzed

Dr. Jones and colleagues conducted a systematic, nonbiased analysis of the prevalence of HPV-positive oropharyngeal squamous cell carcinoma within incident malignancies across all four countries of the United Kingdom over a decade-long period. They determined the HPV status of archival tumor tissue from 1,602 patients who had been diagnosed with oropharyngeal squamous cell carcinoma from 2002 to 2011. Each sample was analyzed using three validated commercial tests for HPV.

Valid results from each of the 3 tests were obtained for samples from 1,474 patients. The prevalence of HPV infection among these patients overall was 51.8%. When the patient samples were considered by the year of disease diagnosis, the proportion of samples testing positive for HPV did not vary significantly between years, remaining static at about 50%.

“The data pertaining to HPV-positive disease provide further evidence in support of a gender-neutral HPV vaccination policy,” said Dr. Jones. “Our hypothesis is that alcohol consumption is driving the increase in HPV-negative disease [in the UK], but we do not have clear evidence for this as yet.”

The authors noted that the greatest limitation of the study was the restriction of analysis to the countries making up the United Kingdom and therefore the lack of generalizability to non-UK populations.

“The magnitude of the increase in incidence of HPV-positive oropharyngeal squamous cell carcinoma in the United States and the United Kingdom over the past few decades is indeed very similar,” said Dr. Jones. “The striking difference in our findings was that the incidence of HPV-negative disease also rose during the study period, while it has been reported to have declined in the United States. These results suggest that exposures to risk factors for HPV-negative disease may vary markedly between the two countries.”

Oropharyngeal squamous cell carcinoma is the most common form of oropharyngeal cancer and includes cancers arising in the tonsil, base of the tongue, soft palate, and the side and back walls of the throat. ■

Disclosure: Dr. Jones has received research funding and honoraria from GlaxoSmithKline and Sanofi Pasteur. He has also been paid for developing and delivering educational presentations for Sanofi Pasteur.

The study was supported by a research grant from GlaxoSmithKline and by sponsorship from the University of Liverpool and Aintree Hospitals NHS Foundation Trust. The Northern Ireland Biobank, which provided access to tissue samples, is funded by the Health and Social Research Development Division of the Public Health Agency.


1. Schache AG, Powell NG, Cuschieri KS, et al: HPV-related oropharyngeal cancer in the United Kingdom. Cancer Res. August 28, 2016 (early release online).

2. National Cancer Institute: Available at ­Accessed October 1, 2016.