Penile cancer and the HPV attributable fraction in Scotland; A retrospective cohort study

Cuschieri, K. and Pan, J. and O Donnell, M. and Kirkwood, K. and Kavanagh, K. and Pollock, K.G. and Bhatia, R. and Graham, S.V. and Wakeham, K. (2021) Penile cancer and the HPV attributable fraction in Scotland; A retrospective cohort study. Journal of Clinical Virology, 134. 104717. ISSN 1386-6532 (

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Background: Penile cancer (PeC) is a highly morbid disease which is rising in certain settings including Scotland. A component of PeC is associated with Human Papillomavirus (HPV) although its influence on clinical outcomes is debatable as is whether the fraction attributable to HPV is increasing. Methods: A total of 122 archived tissue samples derived from patients diagnosed with PeC between 2006–2015 were collated and tested for HPV DNA using molecular PCR. HPV positivity was determined for the overall population and by calendar year of diagnosis to determine any temporal trends. The influence of age, deprivation, smoking, tumour stage and tumour grade on likelihood of HPV positivity was determined by logistic regression. In addition, the influence of HPV status and the other clinical and demographics variables on all-cause death and death from PeC was assessed. Results: HPV was detected in 43 % (95 % CI: 34–52) of penile cancers and the majority of infections were HPV 16. The HPV component of PeC did not increase over the time period (p for linear trend – 0.226). No demographic or clinical variables were associated with HPV positivity neither was HPV status associated with improved all-cause or cancer-specific survival during the follow up period. Conclusion: The rise in PeC in Scotland may not be attributable to a rise in HPV-associated cancer; this is consistent with oropharyngeal cancer (OPC) in the UK where there is an increase in both HPV positive and negative cancer. This work calls for a larger multi centre study to enable further detailed investigation into the implications of HPV infection in PeC.