Understanding HPV-positive carcinoma for better outcomes

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Head and neck cancer is the sixth most common cancer worldwide, and head and neck squamous cell carcinoma (HNSCC) is the most frequent form. Certain subtypes of HNSCC, such as oropharyngeal carcinoma, are infected with human papillomavirus (HPV), and patients with these HPV-positive tumors have a better prognosis than patients without and respond better to chemotherapy and radiotherapy.

To understand why the HPV-positive patients do better, a team from University College London led by Stephan Beck examined the differences in methylation patterns by sequencing HPV-positive and HPV-negative samples, and the results were recently published in Genome Medicine.

Human PapillomavirusAs frozen HNSCC samples are hard to get hold of, the UCL team instead developed a method that uses paraffin-fixed tumor samples, which are widely available. They showed that distinct methylation patterns can be identified based on HPV status. In addition, their data suggest that HPV alters the epigenome by hypermethylation of Polycomb repressive complex 2 target genes, which have been previously linked to tumor progression and metastasis.

The study also provides evidence that when the HPV-16 gene E6 is expressed in HPV-negative HNSCC cell lines, this is sufficient to produce a hypermethylation signature similar to that of HPV-positive carcinomas.

The hope is that an understanding of the methylation differences between the tumor types will allow patients to be stratified to ensure they receive the best treatment.