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Human Papilloma Virus (HPV) status may impact treatment outcomes in patients with pre-cancerous penile lesions (an eUROGEN Study)

International Journal of Impotence Research volume 33, pages 620–626 (2021)Cite this article

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Abstract

Penile intra-epithelial neoplasia (PeIN) is a known precursor for penile cancer. It may be undifferentiated or differentiated. The former is related to high-risk Human Papilloma Virus (HPV) and associated with p16 over-expression. Patients may present with red patches or lesions on the penis which on occasion may affect sexual activity.This study will assess associations between p16 status, patient parameters, treatment choice and outcomes. Data were collected on patients diagnosed with PeIN, who were referred to a single European Network, between 2008 and 2018. The following parameters were collected utilising patient records: demographics, smoking status, performance status, comorbidities, HPV/p16 status, lichen sclerosus (LS) status, treatment and clinical response. Log rank, Kaplan–Meier, Pearson Chi-Squared and Fishers Exact test were utilised to determine significance. One hundred thirty-seven patients were identified with PeIN and no invasive cancer. Staining for p16 was available in 91 patients and 74 patients were p16+. There were no significant differences in disease-free survival (DFS) for smoking status, performance status, comorbidities and lichen sclerosus, although patients with lichen sclerosus tended to recur sooner. Overall, p16+ patients showed significantly better DFS over p16− patients (n = 67; 10.4 vs 7.4 months; p = 0.023). In p16+ patients receiving treatment with imiquimod alone or with surgery, response rates were 100% vs 54% without imiquimod (n = 56; p = 0.017). In p16− patients receiving treatment with imiquimod alone or with surgery, response rates were 100% vs 56% without imiquimod (n = 17; p = 0.99). Overall 13.6% of patients progressed to cancer. The results indicate treatment combinations with immunotherapy tend to provide better responses despite p16 status. Patients with p16+ disease have a longer disease-free survival. Approximately 14% of patients progress to invasive disease. However, given the limitations in this study, further research is required to confirm these findings.

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Fig. 1: Kaplan–Meier DFS plot for PeIN associated with LS: n = 73, p = 0.148.
Fig. 2: Kaplan–Meier DFS plot for PeIN associated with p16 staining: n = 67, p = 0.023.
Fig. 3: Flowchart to demonstrate therapeutic choice of 1st line treatments in patients with penile intra-epithelial neoplasia who had p16 staining available on histopathological report (n = 73).
Fig. 4: Graph showing progression of PeIN to carcinoma.

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Authors and Affiliations

  1. Departments of Urology, The Christie NHS Foundation Trust, Manchester, UK

    Sophie Ashley, Arie Parnham, Maurice Lau & Vijay Sangar

  2. Departments of Histopathology, The Christie NHS Foundation Trust, Manchester, UK

    Jonathan H. Shanks & Pedro Oliveira

  3. Department of Urology, Aintree University Hospitals NHS Foundation Trust, Aintree, UK

    Marc Lucky

  4. Department of Urology, Wirral University Hospitals NHS Foundation Trust, Wirral, UK

    Arie Parnham

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  1. Sophie Ashley
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Correspondence to Vijay Sangar.

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Ashley, S., Shanks, J.H., Oliveira, P. et al. Human Papilloma Virus (HPV) status may impact treatment outcomes in patients with pre-cancerous penile lesions (an eUROGEN Study). Int J Impot Res 33, 620–626 (2021). https://doi.org/10.1038/s41443-020-0327-4

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