Guidelines

Penile Cancer

8. REFERENCES

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8.Sanchez, D.F., et al. Pathological factors, behavior, and histological prognostic risk groups in subtypes of penile squamous cell carcinomas (SCC). Semin Diagn Pathol, 2015. 32: 222. 
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9.Thomas, A., et al. Penile cancer. Nat Rev Dis Primers, 2021. 7: 11. 
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13.Cho, S., et al. Twenty-two-year incidence trend of urological cancers in the Republic of Korea: 1999-2020. Investig Clin Urol, 2024. 65: 23. 
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14.Wnetrzak, I., et al. Epidemiology of penile cancer in Poland compared to other European countries. Cancer Med, 2024. 13: e70092. 
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15.Hansen, B.T., et al. Trends in incidence, mortality and survival of penile squamous cell carcinoma in Norway 1956-2015. Int J Cancer, 2018. 142: 1586. 
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16.Moen, C.A., et al. Penile Cancers Attributed to Human Papillomavirus Are Associated with Improved Survival for Node-positive Patients. Findings from a Norwegian Cohort Study Spanning 50 Years. Eur Urol Oncol, 2024. 7: 778. 
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17.Moen, C.A., et al. The past, present and future of penile cancer in the Nordic countries. Results from NORDCAN. BJUI Compass, 2025. 6: e70041. 
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18.Boehm, W.U., et al. The Clinical Complexity of Penile Cancer: Current Clinical-Epidemiological Data from the Database of the Free State of Saxony/Germany. Urol Int, 2022. 106: 706. 
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19.Vreeburg, M.T.A., et al. Penile cancer care in the Netherlands: increased incidence, centralisation, and improved survival. BJU Int, 2024. 133: 596. 
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20.Cancer Research UK. Penile Cancer incidence trends over time. 2022. 
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21.Daubisse-Marliac, L., et al. Long-term trends in incidence and survival of penile cancer in France. Cancer Epidemiol, 2017. 50: 125. 
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22.Backes, D.M., et al. Systematic review of human papillomavirus prevalence in invasive penile cancer. Cancer Causes Control, 2009. 20: 449. 
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23.Qi, F., et al. Incidence trends and survival outcomes of penile squamous cell carcinoma: evidence from the Surveillance, Epidemiology and End Results population-based data. Ann Transl Med, 2020. 8: 1428. 
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24.Wenzel, M., et al. Temporal trends, tumor characteristics and stage-specific survival in penile non-squamous cell carcinoma vs. squamous cell carcinoma. Cancer Causes Control, 2022. 33: 25. 
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25.Chaux, A., et al. Epidemiologic profile, sexual history, pathologic features, and human papillomavirus status of 103 patients with penile carcinoma. World J Urol, 2013. 31: 861. 
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26.Barnholtz-Sloan, J.S., et al. Incidence trends in primary malignant penile cancer. Urol Oncol, 2007. 25: 361. 
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27.Hartwig, S., et al. Estimation of the epidemiological burden of human papillomavirus-related cancers and non-malignant diseases in men in Europe: a review. BMC Cancer, 2012. 12: 30. 
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28.Olesen, T.B., et al. Prevalence of human papillomavirus DNA and p16(INK4a) in penile cancer and penile intraepithelial neoplasia: a systematic review and meta-analysis. Lancet Oncol, 2019. 20: 145. 
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29.Xu, L., et al. Projected oropharyngeal carcinoma incidence among middle-aged US men. Head Neck, 2019. 41: 3226. 
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30.The Global Cancer Observatory. 26-Penis Fact Sheet. 2022. 
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31.Douglawi, A., et al. Updates on the epidemiology and risk factors for penile cancer. Transl Androl Urol, 2017. 6: 785. 
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32.Deng, X., et al. Trends in Incidence, Mortality, and Survival of Penile Cancer in the United States: A Population-Based Study. Front Oncol, 2022. 12: 891623. 
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33.Lebelo, R.L., et al. Diversity of HPV types in cancerous and pre-cancerous penile lesions of South African men: implications for future HPV vaccination strategies. J Med Virol, 2014. 86: 257. 
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34.Stankiewicz, E., et al. HPV infection and immunochemical detection of cell-cycle markers in verrucous carcinoma of the penis. Mod Pathol, 2009. 22: 1160. 
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35.Kayes, O., et al. Molecular and genetic pathways in penile cancer. Lancet Oncol, 2007. 8: 420. 
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36.Nordenvall, C., et al. Cancer risk among patients with condylomata acuminata. Int J Cancer, 2006. 119: 888. 
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37.Lont, A.P., et al. Presence of high-risk human papillomavirus DNA in penile carcinoma predicts favorable outcome in survival. Int J Cancer, 2006. 119: 1078. 
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38.Bezerra, A.L., et al. Human papillomavirus as a prognostic factor in carcinoma of the penis: analysis of 82 patients treated with amputation and bilateral lymphadenectomy. Cancer, 2001. 91: 2315. 
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39.Bandini, M., et al. Association Between Human Papillomavirus Infection and Outcome of Perioperative Nodal Radiotherapy for Penile Carcinoma. Eur Urol Oncol, 2021. 4: 802. 
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40.Holters, S., et al. Challenging the prognostic impact of the new WHO and TNM classifications with special emphasis on HPV status in penile carcinoma. Virchows Arch, 2019. 475: 211. 
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41.Sand, F.L., et al. Prognostic Significance of HPV and p16 Status in Men Diagnosed with Penile Cancer: A Systematic Review and Meta-analysis. Cancer Epidemiol Biomarkers Prev, 2018. 27: 1123. 
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42.Liu, H., et al. Human papillomavirus as a favorable prognostic factor in a subset of head and neck squamous cell carcinomas: A meta-analysis. J Med Virol, 2017. 89: 710. 
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43.Urbute, A., et al. Prognostic Significance of HPV DNA and p16(INK4a) in Anal Cancer: A Systematic Review and Meta-Analysis. Cancer Epidemiol Biomarkers Prev, 2020. 29: 703. 
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44.Zhang, J., et al. Prognostic Significance of P16(INK4a) Expression in Penile Squamous Cell Carcinoma: A Meta-Analysis with Trial Sequential Analysis. Biomed Res Int, 2018. 2018: 8345893. 
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45.Chahoud, J., et al. Prognostic Significance of p16 and Its Relationship with Human Papillomavirus Status in Patients with Penile Squamous Cell Carcinoma: Results of 5 Years Follow-Up. Cancers (Basel), 2022. 14. 
https://www.ncbi.nlm.nih.gov/pubmed/36551510

46.Sand, F.L., et al. The prognostic value of p16 and p53 expression for survival after vulvar cancer: A systematic review and meta-analysis. Gynecol Oncol, 2019. 152: 208. 
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47.Mirghani, H., et al. Is there an increased risk of cancer among spouses of patients with an HPV-related cancer: A systematic review. Oral Oncol, 2017. 67: 138. 
https://www.ncbi.nlm.nih.gov/pubmed/28351568

48.de Bruijn, R.E., et al. Patients with penile cancer and the risk of (pre)malignant cervical lesions in female partners: a retrospective cohort analysis. BJU Int, 2013. 112: 905. 
https://www.ncbi.nlm.nih.gov/pubmed/23905914

49.Elst, L., et al. Single-cell Atlas of Penile Cancer Reveals TP53 Mutations as a Driver of an Aggressive Phenotype, Irrespective of Human Papillomavirus Status, and Provides Clues for Treatment Personalization. Eur Urol, 2024. 86: 114. 
https://www.ncbi.nlm.nih.gov/pubmed/38670879

50.Sand, F.L., et al. The prognostic value of p53 and Ki-67 expression status in penile cancer: a systematic review and meta-analysis. Pathology, 2025. 57: 276. 
https://www.ncbi.nlm.nih.gov/pubmed/39939228

51.Chahoud, J., et al. TP53 Mutations Emerge as a Critical Biomarker in Penile Cancer, Superseding Human Papillomavirus Status. Eur Urol, 2024. 86: 128. 
https://www.ncbi.nlm.nih.gov/pubmed/38749849

52.Monteiro, F.S.M., et al. Molecular characterization of metastatic penile squamous cell carcinoma in developing countries and its impact on clinical outcomes: LACOG 2018 translational study. Oncologist, 2025. 30. 
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53.Li, Y., et al. Impact of TP53 Alterations on Clinical Outcomes in Penile Squamous Cell Carcinoma. Clin Genitourin Cancer, 2025. 23: 102323. 
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54.Nazha, B., et al. Comprehensive genomic profiling of penile squamous cell carcinoma and the impact of human papillomavirus status on immune-checkpoint inhibitor-related biomarkers. Cancer, 2023. 129: 3884. 
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55.Starita, N., et al. Mutations in the telomerase reverse transcriptase promoter and PIK3CA gene are common events in penile squamous cell carcinoma of Italian and Ugandan patients. Int J Cancer, 2022. 150: 1879. 
https://www.ncbi.nlm.nih.gov/pubmed/35253909

56.da Silva Santos, R., et al. Hypomethylation at H19DMR in penile squamous cell carcinoma is not related to HPV infection. Epigenetics, 2024. 19: 2305081. 
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57.Ermakov, M.S., et al. Different Mutational Landscapes in Human Papillomavirus-Induced and Human Papillomavirus-Independent Invasive Penile Squamous Cell Cancers. Mod Pathol, 2023. 36: 100250. 
https://www.ncbi.nlm.nih.gov/pubmed/37353203

58.Hrudka, J., et al. Immune cell infiltration, tumour budding, and the p53 expression pattern are important predictors in penile squamous cell carcinoma: a retrospective study of 152 cases. Pathology, 2023. 55: 637. 
https://www.ncbi.nlm.nih.gov/pubmed/37316384

59.Necchi, A., et al. Genomic Profiles and Clinical Outcomes of Penile Squamous Cell Carcinoma With Elevated Tumor Mutational Burden. JAMA Netw Open, 2023. 6: e2348002. 
https://www.ncbi.nlm.nih.gov/pubmed/38150257

60.Trias, I., et al. p53 Immunohistochemistry Defines a Subset of Human Papillomavirus-Independent Penile Squamous Cell Carcinomas With Adverse Prognosis. Am J Surg Pathol, 2024. 48: 1439. 
https://www.ncbi.nlm.nih.gov/pubmed/39040011

61.Zhang, J., et al. The efficacy of vaccination to prevent human papilloma viruses infection at anal and oral: a systematic review and meta-analysis. Public Health, 2021. 196: 165. 
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62.Harder, T., et al. Efficacy, effectiveness and safety of vaccination against human papillomavirus in males: a systematic review. BMC Med, 2018. 16: 110. 
https://www.ncbi.nlm.nih.gov/pubmed/30016957

63.Liao, C.I., et al. Trends in Human Papillomavirus-Associated Cancers, Demographic Characteristics, and Vaccinations in the US, 2001-2017. JAMA Netw Open, 2022. 5: e222530. 
https://www.ncbi.nlm.nih.gov/pubmed/35294540

64.Elst, L., et al. HPV Vaccination: Does It Have a Role in Preventing Penile Cancer and Other Preneoplastic Lesions? Semin Oncol Nurs, 2022. 38: 151284. 
https://www.ncbi.nlm.nih.gov/pubmed/35577640

65.Tsen, H.F., et al. Risk factors for penile cancer: results of a population-based case-control study in Los Angeles County (United States). Cancer Causes Control, 2001. 12: 267. 
https://www.ncbi.nlm.nih.gov/pubmed/11405332

66.Koifman, L., et al. Epidemiological aspects of penile cancer in Rio de Janeiro: evaluation of 230 cases. Int Braz J Urol, 2011. 37: 231. 
https://www.ncbi.nlm.nih.gov/pubmed/21557840

67.Van Howe, R.S., et al. The carcinogenicity of smegma: debunking a myth. J Eur Acad Dermatol Venereol, 2006. 20: 1046. 
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68.Daling, J.R., et al. Penile cancer: importance of circumcision, human papillomavirus and smoking in in situ and invasive disease. Int J Cancer, 2005. 116: 606. 
https://www.ncbi.nlm.nih.gov/pubmed/15825185

69.Velazquez, E.F., et al. Limitations in the interpretation of biopsies in patients with penile squamous cell carcinoma. Int J Surg Pathol, 2004. 12: 139. 
https://www.ncbi.nlm.nih.gov/pubmed/15173919

70.Velazquez, E.F., et al. Lichen sclerosus in 68 patients with squamous cell carcinoma of the penis: frequent atypias and correlation with special carcinoma variants suggests a precancerous role. Am J Surg Pathol, 2003. 27: 1448. 
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71.Teichman, J.M., et al. Noninfectious penile lesions. Am Fam Physician, 2010. 81: 167. 
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72.Renaud-Vilmer, C., et al. Analysis of alterations adjacent to invasive squamous cell carcinoma of the penis and their relationship with associated carcinoma. J Am Acad Dermatol, 2010. 62: 284. 
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73.Straub Hogan, M.M., et al. Pathological characterization and clinical outcome of penile intraepithelial neoplasia variants: a North American series. Mod Pathol, 2022. 35: 1101. 
https://www.ncbi.nlm.nih.gov/pubmed/35190664

74.Menon, S., et al. International Society of Urological Pathology (ISUP) Multidisciplinary Consensus on Premalignant and Putative Precursor Lesions of Penile Cancer: Working Group 5 report on Terminology, Grading, and Molecular Testing Practices. Am J Surg Pathol, 2025. 
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75.Moch, H., et al. The 2022 World Health Organization Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours. Eur Urol, 2022. 82: 458. 
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76.Chaux, A., et al. Metastatic tumors to the penis: a report of 17 cases and review of the literature. Int J Surg Pathol, 2011. 19: 597. 
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77.Ebel, J.J., et al. Whole-mount evaluation of penectomies for penile cancer: feasibility, cost and comparison to routine sectioning. Histopathology, 2013. 63: 64. 
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78.Corbishley C., et al. Standards and datasets for reporting cancers Dataset for penile and distal urethral cancer histopathology reports. 2022. 
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79.Tang, V., et al. Should centralized histopathological review in penile cancer be the global standard? BJU Int, 2014. 114: 340. 
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80.Vanthoor, J., et al. Making surgery safer by centralization of care: impact of case load in penile cancer. World J Urol, 2020. 38: 1385. 
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81.Aumayr, K., et al. P16INK4A immunohistochemistry for detection of human papilloma virus-associated penile squamous cell carcinoma is superior to in-situ hybridization. Int J Immunopathol Pharmacol, 2013. 26: 611. 
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82.Bezerra, S.M., et al. Human papillomavirus infection and immunohistochemical p16(INK4a) expression as predictors of outcome in penile squamous cell carcinomas. Hum Pathol, 2015. 46: 532. 
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83.Mannweiler, S., et al. Two major pathways of penile carcinogenesis: HPV-induced penile cancers overexpress p16ink4a, HPV-negative cancers associated with dermatoses express p53, but lack p16ink4a overexpression. J Am Acad Dermatol, 2013. 69: 73. 
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84.Corbishley, M.C., et al. Carcinoma of the Penis and Distal Urethra Histopathology Reporting Guide 1st edition. International Collaboration on Cancer Reporting; Sydney, Australia. ISBN: 978-1-925687-05-7. 2017. 
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85.Guimaraes, G.C., et al. Front pattern of invasion in squamous cell carcinoma of the penis: new prognostic factor for predicting risk of lymph node metastases. Urology, 2006. 68: 148. 
https://www.ncbi.nlm.nih.gov/pubmed/16844455

86.Sanchez, D.F., et al. What Is New in the Pathologic Staging of Penile Carcinoma in the 8th Edition of AJCC TNM Model: Rationale for Changes With Practical Stage-by-stage Category Diagnostic Considerations. Adv Anat Pathol, 2021. 28: 209. 
https://www.ncbi.nlm.nih.gov/pubmed/34050061

87.Sali, A.P., et al. Histopathological risk scoring system as a tool for predicting lymph nodal metastasis in penile squamous cell carcinoma. Pathology, 2019. 51: 696. 
https://www.ncbi.nlm.nih.gov/pubmed/31635947

88.Winters, B.R., et al. Predictors of Nodal Upstaging in Clinical Node Negative Patients With Penile Carcinoma: A National Cancer Database Analysis. Urology, 2016. 96: 29. 
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89.Feng, M.A., et al. Concordance of lymphovascular invasion diagnosed in penile carcinoma with and without the immunohistochemical markers ERG and CD31. Histol Histopathol, 2016. 31: 293. 
https://www.ncbi.nlm.nih.gov/pubmed/26452171

90.Dorofte, L., et al. Low level of interobserver concordance in assessing histological subtype and tumor grade in patients with penile cancer may impair patient care. Virchows Arch, 2022. 480: 879. 
https://www.ncbi.nlm.nih.gov/pubmed/34889977

91.Aita, G., et al. Pattern of invasion is the most important prognostic factor in patients with penile cancer submitted to lymph node dissection and pathological absence of lymph node metastasis. BJU Int, 2015. 116: 584. 
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92.Dorofte, L., et al. New histological risk grading system for prediction of lymph node metastasis in patients with penile cancer. Virchows Arch, 2025. 486: 759. 
https://www.ncbi.nlm.nih.gov/pubmed/39251424

93.Cubilla, A.L. The role of pathologic prognostic factors in squamous cell carcinoma of the penis. World J Urol, 2009. 27: 169. 
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94.Zekan, D.S., et al. Prognostic predictors of lymph node metastasis in penile cancer: a systematic review. Int Braz J Urol, 2021. 47: 943. 
https://www.ncbi.nlm.nih.gov/pubmed/33650835

95.Fankhauser, C.D., et al. Lymphovascular and perineural invasion are risk factors for inguinal lymph node metastases in men with T1G2 penile cancer. J Cancer Res Clin Oncol, 2022. 148: 2231. 
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96.Brierley, J., et al., TNM Classification of Malignant Tumours, 9th Edn. 2025. 
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97.Li, Z., et al. Corpora Cavernos invasion vs. Corpus Spongiosum invasion in Penile Cancer: A systematic review and meta-analysis. J Cancer, 2021. 12: 1960. 
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98.Sali, A.P., et al. A comparative study of AJCC and the modified staging system in pT2/pT3 penile squamous cell carcinoma - a validation on an external data set. Histopathology, 2022. 80: 566. 
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99.Zhang, Z.L., et al. The importance of extranodal extension in penile cancer: a meta-analysis. BMC Cancer, 2015. 15: 815. 
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100.Gunia, S., et al. Does the width of the surgical margin of safety or premalignant dermatoses at the negative surgical margin affect outcome in surgically treated penile cancer? J Clin Pathol, 2014. 67: 268. 
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101.Wang, J.Y., et al. Prognostic significance of the degree of extranodal extension in patients with penile carcinoma. Asian J Androl, 2014. 16: 437. 
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102.Chaux, A., et al. The prognostic index: a useful pathologic guide for prediction of nodal metastases and survival in penile squamous cell carcinoma. Am J Surg Pathol, 2009. 33: 1049. 
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103.Zito Marino, F., et al. Discrepancy of p16 immunohistochemical expression and HPV RNA in penile cancer. A multiplex in situ hybridization/immunohistochemistry approach study. Infect Agent Cancer, 2021. 16: 22. 
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104.Cubilla, A.L., et al. Value of p16(INK)(4)(a) in the pathology of invasive penile squamous cell carcinomas: A report of 202 cases. Am J Surg Pathol, 2011. 35: 253. 
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105.Canete-Portillo, S., et al. Report From the International Society of Urological Pathology (ISUP) Consultation Conference on Molecular Pathology of Urogenital Cancers V: Recommendations on the Use of Immunohistochemical and Molecular Biomarkers in Penile Cancer. Am J Surg Pathol, 2020. 44: e80. 
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106.Amin, M.B., et al. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin, 2017. 67: 93. 
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107.Velazquez, E.F., et al. Histologic grade and perineural invasion are more important than tumor thickness as predictor of nodal metastasis in penile squamous cell carcinoma invading 5 to 10 mm. Am J Surg Pathol, 2008. 32: 974. 
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108.Leijte, J.A., et al. Evaluation of current TNM classification of penile carcinoma. J Urol, 2008. 180: 933. 
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109.Sun, M., et al. Development and external validation of a prognostic tool for prediction of cancer-specific mortality after complete loco-regional pathological staging for squamous cell carcinoma of the penis. BJU Int, 2015. 116: 734. 
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110.Li, Z.S., et al. Modification of N staging systems for penile cancer: a more precise prediction of prognosis. Br J Cancer, 2015. 113: 1746. 
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111.Chipollini, J., et al. Patient presentation, differential diagnosis, and management of penile lesions. Can Urol Assoc J, 2019. 13: S2. 
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112.Lont, A.P., et al. A comparison of physical examination and imaging in determining the extent of primary penile carcinoma. BJU Int, 2003. 91: 493. 
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113.Bertolotto, M., et al. Primary and secondary malignancies of the penis: ultrasound features. Abdom Imaging, 2005. 30: 108. 
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114.Kayes, O., et al. The role of magnetic resonance imaging in the local staging of penile cancer. Eur Urol, 2007. 51: 1313. 
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115.Hanchanale, V., et al. The accuracy of magnetic resonance imaging (MRI) in predicting the invasion of the tunica albuginea and the urethra during the primary staging of penile cancer. BJU Int, 2016. 117: 439. 
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116.Krishna, S., et al. Diagnostic Accuracy of MRI in Local Staging (T Category) of Penile Cancer and the Value of Artificial Erection: A Systematic Review and Meta-Analysis. AJR Am J Roentgenol, 2022. 219: 28. 
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117.Bozzini, G., et al. Role of Penile Doppler US in the Preoperative Assessment of Penile Squamous Cell Carcinoma Patients: Results From a Large Prospective Multicenter European Study. Urology, 2016. 90: 131. 
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