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-based combination therapy

Wei, Lichao1; Li, Zaishang2,3; Guo, Shengjie1; Ma, Huali4; Shi, Yanxia5; An, Xin5; Huang, Kangbo1; Xiong, Longbin1; Xue, Ting1; Zhang, Zhiling1; Yao, Kai1; Luo, Junhang6,7; Han, Hui1

2024-05-01

10.1002/cncr.35177

CANCER   影响因子和分区

0008-543X

1097-0142

Background: Penile squamous cell carcinoma (PSCC) is a human papillomavirus (HPV)-associated 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-based combination therapy (PCT).Methods: 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-free survival (PFS), and overall survival (OS) in the HPV+ and HPV- groups were compared. Additionally, bulk RNA sequencing was performed to investigate the potential impact of HPV on the immune microenvironment in advanced PSCC.Results: Among patients receiving first-line PCT, ORR (91.7% vs. 64.6%, p = .014) and DCR (100.0% vs. 79.2%, p = .025) in the HPV+ group were higher compared to the HPV- group. Kaplan-Meier curves demonstrated that the HPV+ group exhibited superior PFS (p = .005) and OS (p = .004) for patients in the first-line setting. However, these advantages of HPV infection were not observed in multi-line PCT (p > .050). HPV status remained an independent prognostic factor for predicting better ORR (p = .024), PFS (p = .002), and OS (p = .020) in the multivariate analyses. Landmark analyses showed that the HPV-induced superiority of PFS occurred at an early stage (within 3 months) and OS occurred at a relatively late stage (within 9 months). Bioinformatic analyses identified potential immune-activated genes (GLDC, CYP4F12, etc.) and pathways (RAGE, PI3K/AKT, etc.), antitumor immune cell subtypes, and lower tumor immune dysfunction and exclusion scores in HPV+ tissues.Conclusions: HPV infection may confer treatment efficacy and survival benefits in patients with advanced PSCC receiving first-line PCT because of the possible stimulation of the antitumor immune microenvironment.

advanced penile squamous cell carcinoma combination therapy efficacy human papillomavirus immune microenvironment PD1 inhibitor prognosis

SCI

英语

其他

Guangdong Province Nature Foundation of China Project["2021A1515220182","2022A1515012321","2022A1515012200"] ; Science and Technology Planning Project of Shenzhen Municipality (CN)[JCYJ20190807145409328] ; null[RCYX20221008093032008]

Oncology

Oncology

WOS:001134175400001

WILEY

CLINICAL MEDICINE

Web of Science

1.Sun Yat Sen Univ, Guangdong Prov Clin Res Ctr Canc, Dept Urol, State Key Lab Oncol South China,Canc Ctr, 651 Dongfeng Rd East, Guangzhou 510060, Peoples R China
2.Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Dept Urol, Affiliated Hosp 1, Shenzhen, Peoples R China
3.Jinan Univ, Clin Coll 2, Dept Urol, Shenzhen, Peoples R China
4.Sun Yat Sen Univ, Guangdong Prov Clin Res Ctr Canc, Dept Radiol, State Key Lab Oncol South China,Canc Ctr, Guangzhou, Peoples R China
5.Sun Yat Sen Univ, Guangdong Prov Clin Res Ctr Canc, Dept Med Oncol, State Key Lab Oncol South China,Canc Ctr, Guangzhou, Peoples R China
6.Sun Yat Sen Univ, Affiliated Hosp 1, Dept Urol, 58 Zhongshan Rd East, Guangzhou 510080, Peoples R China
7.Sun Yat Sen Univ, Affiliated Hosp 1, Inst Precis Med, Guangzhou, Peoples R China

Wei, Lichao,Li, Zaishang,Guo, Shengjie,et al. 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-based combination therapy[J]. CANCER,2024,130(9).

Wei, Lichao.,Li, Zaishang.,Guo, Shengjie.,Ma, Huali.,Shi, Yanxia.,...&Han, Hui.(2024).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-based combination therapy.CANCER,130(9).

Wei, Lichao,et al."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-based combination therapy".CANCER 130.9(2024).