{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:49:04Z","timestamp":1790124544170,"version":"4.0.1"},"reference-count":38,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,12,29]],"date-time":"2023-12-29T00:00:00Z","timestamp":1703808000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Penile squamous cell carcinoma (PSCC) is a human papillomavirus (HPV)\u2010associated malignancy. Immunotherapy is emerging as a potential treatment for advanced PSCC. In this study, the authors analyzed the association of HPV status with outcomes and the immune microenvironment in patients with advanced PSCC undergoing programmed cell death protein 1 (PD1) inhibitor\u2013based combination therapy (PCT).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>HPV status was assessed using quantitative polymerase chain reaction in 87 patients with advanced PSCC treated with PCT. Objective response rate (ORR), disease control rate (DCR), progression\u2010free survival (PFS), and overall survival (OS) in the HPV+ and HPV\u2013 groups were compared. Additionally, bulk RNA sequencing was performed to investigate the potential impact of HPV on the immune microenvironment in advanced PSCC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among patients receiving first\u2010line PCT, ORR (91.7% vs. 64.6%, <jats:italic>p<\/jats:italic>\u00a0=\u00a0.014) and DCR (100.0% vs. 79.2%, <jats:italic>p<\/jats:italic>\u00a0=\u00a0.025) in the HPV+\u00a0group were higher compared to the HPV\u2013 group. Kaplan\u2013Meier curves demonstrated that the HPV+\u00a0group exhibited superior PFS (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.005) and OS (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.004) for patients in the first\u2010line setting. However, these advantages of HPV infection were not observed in multi\u2010line PCT (<jats:italic>p<\/jats:italic>\u00a0&gt;\u00a0.050). HPV status remained an independent prognostic factor for predicting better ORR (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.024), PFS (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.002), and OS (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.020) in the multivariate analyses. Landmark analyses showed that the HPV\u2010induced superiority of PFS occurred at an early stage (within 3\u00a0months) and OS occurred at a relatively late stage (within 9\u00a0months). Bioinformatic analyses identified potential immune\u2010activated genes (GLDC, CYP4F12, etc.) and pathways (RAGE, PI3K\/AKT, etc.), antitumor immune cell subtypes, and lower tumor immune dysfunction and exclusion scores in HPV+\u00a0tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>HPV infection may confer treatment efficacy and survival benefits in patients with advanced PSCC receiving first\u2010line PCT because of the possible stimulation of the antitumor immune microenvironment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Plain Language Summary<\/jats:title><jats:p>\n<jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Human papillomavirus (HPV) infection may induce better objective response rate, progression\u2010free survival (PFS), and overall survival (OS) for advanced penile squamous cell carcinoma (PSCC) patients receiving first\u2010line programmed cell death protein 1 inhibitor\u2013based combination therapy (PCT) instead of multi\u2010line PCT.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>HPV infection\u2010induced PFS advantage occurs at an early stage (within 3\u00a0months) whereas OS superiority occurs at a relatively late stage (within 9\u00a0months).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Antitumor immune microenvironment could be stimulated by HPV infection in advanced PSCC tissues.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.35177","type":"journal-article","created":{"date-parts":[[2023,12,29]],"date-time":"2023-12-29T12:15:35Z","timestamp":1703852135000},"page":"1650-1662","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Human papillomavirus infection affects treatment outcomes and the immune microenvironment in patients with advanced penile squamous cell carcinoma receiving programmed cell death protein 1 inhibitor\u2013based combination therapy"],"prefix":"10.1002","volume":"130","author":[{"given":"Lichao","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Urology Sun Yat\u2010sen University Cancer Center State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaishang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Urology Shenzhen People\u2019s Hospital The First Affiliated Hospital of Southern University of Science and Technology  Shenzhen China"},{"name":"Department of Urology The Second Clinical College of Jinan University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7953-8775","authenticated-orcid":false,"given":"Shengjie","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Urology Sun Yat\u2010sen University Cancer Center State Key Laboratory 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Yat\u2010sen University Cancer Center State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangbo","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Urology Sun Yat\u2010sen University Cancer Center State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longbin","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Urology Sun Yat\u2010sen University Cancer Center State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Urology Sun Yat\u2010sen University Cancer 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