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Prevalence of human papillomavirus and implication on survival in Chinese penile cancer

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We assessed the prevalence of HPV DNA in a large series of Chinese penile cancer and examine its association with the histological subtype, p16INK4a expression, and prognosis. We pathologically categorized 226 invasive penile squamous cell carcinomas and assessed HPV genotyping by real-time PCR and p16INK4a immunohistochemistry. The results were correlated with histopathological and clinical parameters and disease-specific survival (DSS). HPV DNA was detected in 32.7% (74/226) of penile cancer cases. The most frequent genotype was HPV 16 (64/74, 86.5%), followed by HPV 18 (6/74, 8.1%). Fifty-nine (26.1%) cases were positive for the p16INK4a expression, and p16INK4a expression had a sensitivity of 56.8% (95% CI, 45.2–68.3%) and a specificity of 88.8% (95% CI, 83.8–93.9%) for defining HPV status. HPV DNA (P = 0.019), p16INK4a (P = 0.038), age (P = 0.018), grade of differentiation (P = 0.001), lymph nodes (P < 0.001), T stage (P < 0.001), M stage (P < 0.001), and lymphovascular invasion (LVI, P = 0.001) were prognostic factors for DSS. HPV-positivity (HR 0.334; 95% CI, 0.158–0.705, P = 0.004) was still a significant prognostic factor for DSS in the multivariate Cox regression model. HPV DNA was observed in one third of Chinese penile carcinoma cases. The p16INK4a expression can indicate high-risk human papillomavirus (HR-HPV). HPV-positive penile tumors confer a survival benefit over HPV-negative tumors.

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This study was supported by the grant from the Nature Science Foundation of China (No. 81872085) and Sun Yat-sen University Cancer Center Medical scientist training program (No.14zxqk08).

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Authors and Affiliations



Conceptualization: Chengbiao Chu, Kai Yao, Yun Cao; Methodology: Chengbiao Chu, Keming Chen, Xingliang Tan, Jiangli Lu, Yuanzhong Yang, YiJun Zhang; Formal analysis and investigation: Chengbiao Chu, Keming Chen; Writing, original draft preparation: Chengbiao Chu; Writing, review and editing: Chengbiao Chu, Kai Yao, Yun Cao; Funding acquisition: Kai Yao, Yun Cao; Resources: Chengbiao Chu, Xingliang Tan, Kai Yao, Yun Cao; all authors read and approved the final manuscript.

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Correspondence to Kai Yao or Yun Cao.

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The study protocol was approved by Independent Ethics Committee of Sun Yat-sen University Cancer Center.

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The authenticity of this article has been validated by uploading the key raw data onto the Research Data Deposit public platform (, with the approval RDD number as RDDB2019000656.

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Chu, C., Chen, K., Tan, X. et al. Prevalence of human papillomavirus and implication on survival in Chinese penile cancer. Virchows Arch 477, 667–675 (2020).

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