Ashley Sophie, Shanks Jonathan H, Oliveira Pedro, Lucky Marc, Parnham Arie, Lau Maurice, Sangar Vijay
Departments of Urology, The Christie NHS Foundation Trust, Manchester, UK.
Departments of Histopathology, The Christie NHS Foundation Trust, Manchester, UK.
Int J Impot Res. 2021 Sep;33(6):620-626. doi: 10.1038/s41443-020-0327-4. Epub 2020 Jul 24.
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.
阴茎上皮内瘤变（PeIN）是阴茎癌已知的癌前病变。它可以是未分化型或分化型。前者与高危人乳头瘤病毒（HPV）有关，并伴有p16过表达。患者阴茎上可能出现红色斑块或病变，有时可能影响性活动。本研究将评估p16状态、患者参数、治疗选择和预后之间的关联。收集了2008年至2018年间被转诊至单一欧洲网络的诊断为PeIN的患者的数据。利用患者记录收集了以下参数：人口统计学信息、吸烟状况、体能状态、合并症、HPV/p16状态、硬化性苔藓（LS）状态、治疗及临床反应。采用对数秩检验、Kaplan-Meier法、Pearson卡方检验和Fisher精确检验来确定显著性。共识别出137例患有PeIN且无浸润性癌的患者。91例患者可进行p16染色，其中74例患者p16呈阳性。吸烟状况、体能状态、合并症和硬化性苔藓患者的无病生存期（DFS）无显著差异，不过患有硬化性苔藓的患者往往复发更早。总体而言，p16阳性患者的DFS显著优于p16阴性患者（n = 67；10.4个月对7.4个月；p = 0.023）。在单独接受咪喹莫特治疗或联合手术治疗的p16阳性患者中，有咪喹莫特组的缓解率为100%，无咪喹莫特组为54%（n = 56；p = 0.017）。在单独接受咪喹莫特治疗或联合手术治疗的p16阴性患者中，有咪喹莫特组的缓解率为100%，无咪喹莫特组为56%（n = 17；p = 0.99）。总体而言，13.6%的患者进展为癌症。结果表明，无论p16状态如何，免疫治疗联合方案往往能提供更好的反应。p16阳性疾病患者的无病生存期更长。约14%的患者进展为浸润性疾病。然而，鉴于本研究存在局限性，需要进一步研究来证实这些发现。
