Parallels and divergence in head and neck and cervical cancer

This paper concerns a rare disease – human papillomavirus (HPV)-negative cervical cancer. Rodriguez-Carunchio et al. describe the clinical outcomes of HPV-negative adenocarcinoma and squamous cell carcinoma of the cervix. HPV-negative cervical cancer had a much poorer prognosis in terms of disease-free survival compared with HPV-positive cervical cancer (P = 0.010). However, overall survival was not different, possibly due to the low number of HPV-negative patients studied. These data are similar to established observations in head and neck cancer. The primary head and neck subsite associated with HPV is the oropharynx. Approximately two-thirds of oropharyngeal SCC (OPSCC) is driven by HPV type 16. HPV-16-positive disease tends to occur in a young, non-smoking, non-heavy-drinking population in contrast to the traditional head and neck cancer patients. The HPV status of OPSCC has a far greater impact on the overall survival of the patient than any chemotherapy drug. HPV-16-positive disease responds remarkably well to current standard treatment (chemoradiotherapy or laser excision +/− adjuvant radiotherapy). For example, response rates of 82% in stage III/IV HPV-positive patients compared to 55% in HPV-negative patients have been demonstrated (Fakhry et al., J Natl Cancer Inst 2008; 100: 261–9). HPV-positive tumours appear to be genomically simpler to HPV-negative tumours. The cancer genome atlas and other studies have demonstrated less intra-tumoural heterogeneity and fewer mutations within HPV-positive tumours. Cancer is a genetic disease that confers a selective advantage for the malignant cell. That HPV-positive tumours possess fewer advantageous mutations and fewer clonal populations to develop resistance to therapies may well be the underlying cause of their improved response to treatment. The incidence of OPSCC is increasing, thought to be due to growing numbers of HPV-16-driven tumours. Within HPV-16-positive OPSCC, different risk groups have been identified. A retrospective analysis of a randomised controlled trial found that smokers had a poorer prognosis (Ang et al., N Engl J Med 2010; 363: 24–35). Another study showed that the number of tumour-infiltrating lymphocytes (TIL) correlates with survival (Ward et al., Br J Cancer 2014; 110: 489–500). Currently HPV-status does not guide treatment, although clinical trials incorporating HPV-status to modify treatment regimens are underway. In cervical cancer, HPV status does not influence clinical decision-making, as HPV-negative disease is rare. Moving forwards, it is important that regional centres evaluate and publish the outcomes of their HPV-negative cervical cancer patients. This will facilitate the rationalisation of adjuvant treatment strategies according to individual patient factors, including HPV status. None. This author is currently funded by grants from Leeds Charitable Foundation, the Mason Medical Research Foundation and the Royal College of Physicians & Surgeons of Glasgow. The funders had no role in the study design, data collection, analysis, interpretation or writing of this report.