TITLE PAGE:Title:Letter to the Editor: Human papillomavirus 16 infection in patients with esophageal squamous cell carcinoma undergoing chemoradiotherapyAuthors:Shih-Kuei Peng1James Cheng-Chung Wei2Qi Mei3,4Affiliations:1Department of Anesthesiology, Chung Shan Medical University Hospital, Taichung, Taiwan2Chung Shan Medical University, Taichung, Taiwan3Cancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China4Department of Oncology，Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, Wuhan, People’s Republic of China.CorrespondenceShih-Kuei Department of Anesthesiology, Chung Shan Medical University Hospital, 40201 Taichung, Taiwan.Email: [email protected] address of the corresponding author:James Cheng-Chung Wei: [email protected] Mei: [email protected] Penghttps://orcid.org/0009-0002-2038-8594Letter to the Editor: Human papillomavirus 16 infection in patients with esophageal squamous cell carcinoma undergoing chemoradiotherapyDear Editor,We are writing to express our appreciation and to discuss the recent study published in your journal titled ”Survival benefits of human papillomavirus 16 infection in patients with esophageal squamous cell carcinoma undergoing chemoradiotherapy.1” This study provides insightful data into the prognostic impact of HPV 16 on ESCC treated with chemoradiotherapy, emphasizing its potential role in personalized treatment strategies. While the findings are promising, showing that HPV 16-positive patients had significantly longer overall survival, we would like to raise some concerns regarding the study’s limitations which might affect the interpretation of these results.Firstly, the retrospective nature of the study may contribute to inherent biases such as selection and recall bias2-4. Additionally, the study’s single-center design may not reflect a broader demographic, which could limit the generalizability of the findings.Furthermore, it is crucial to consider the external validation of these results to strengthen the study’s conclusions. The impact of HPV 16 on survival seems substantial, but without validation from external cohorts, the findings remain provisional. HPV virus infection can sometimes have local variation on genotypes, serotypes, and clinical phenotypes.Finally, while the study offers valuable insights into the role of HPV 16 in ESCC, further prospective studies with diverse and larger populations are necessary to confirm these findings and to consider them in clinical applications5,6. We appreciate the efforts of the authors and look forward to future research that may expand on these initial findings.CONFLICT OF INTEREST STATEMENTThe authors declare no conflict of interest.Shih-Kuei Peng1James Cheng-Chung Wei2Qi Mei3,41Department of Anesthesiology, Chung Shan Medical University Hospital, Taichung, Taiwan2Chung Shan Medical University, Taichung, Taiwan3Cancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China4Department of Oncology，Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, Wuhan, People’s Republic of China.Correspondence: James Cheng-Chung Wei and Qi Mei contribute equallyORCIDShih-Kuei Penghttps://orcid.org/0009-0002-2038-8594REFERENCESQu F, Ji C, Wang Y, et al. Survival benefits of human papillomavirus 16 infection in patients with esophageal squamous cell carcinoma undergoing chemoradiotherapy: A retrospective cohort study. J Med Virol. 2024;96(4): e29592. doi: 10.1002/jmv.29592.Morgan E, Soerjomataram I, Rumgay H, et al. The global landscape of esophageal squamous cell carcinoma and esophageal adenocarcinoma incidence and mortality in 2020 and projections to 2040: new estimates from GLOBOCAN 2020. Gastroenterology. 2022;163(3):649‐658.e2.Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209‐249.Lagergren J, Smyth E, Cunningham D, Lagergren P. Oesophageal cancer.Lancet. 2017;390(10110):2383‐2396.Spiotto MT, Taniguchi CM, Klopp AH, et al. Biology of the radio‐ and Chemo‐Responsiveness in HPV malignancies. Semin Radiat Oncol.2021;31(4):274‐285.Wang WL, Wang YC, Lee CT, et al. The impact of human papillomavirus infection on the survival and treatment response of patients with esophageal cancers. J Dig Dis. 2015;16(5):256‐263.