Human papillomavirus (HPV) is a sexually transmitted pathogen that can cause HPV-associated cancers in both men and women. Cervical cancer primarily associated with HPV, and anogenital cancers such as vaginal, vulvar, penile, and anal cancers are also linked to HPV. Interestingly, there are an increasing number of head and neck squamous cell carcinoma (HNSCC) cases that are attributed to HPV infection (Rettig et al., 2022). Surprisingly, HPV-positive HNSCC patients tend to have better prognosis and survival rates compared to HPV-negative patients, although the reasons for this remain unclear (Gameiro et al., 2022, Williams et al., 2022). Therefore, investigating the biological characteristics and metabolic regulation mechanisms of HPV-positive HNSCC is of growing importance.

Metabolic reprogramming is a crucial characteristic of cancer, involving alterations in glucose, lipid, and amino acid metabolism (AAM) (Tripathi et al., 2012; Y. H. Wang et al., 2022; Yang et al., 2020). Cancer cells adapt their metabolic pathways to cope with environmental stress and meet their growth requirements. Beyond glucose, elevated levels of glutamate, glutamine, aspartate, and alanine in HNSCC cells indicate a dependency on glutamine degradation for carbon and nitrogen sources (Lee et al., 2022, Miao et al., 2022, Ohashi et al., 2022, Somashekar et al., 2011). Consequently, many cancers exhibit an increased demand for specific amino acids and gradually rely on upregulated exogenous supply or de novo synthesis (Yang et al., 2019). Amino acid metabolism, in conjunction with glucose metabolism, provides cells with essential energy and nutrients, playing a pivotal role in maintaining cell growth, proliferation, and survival (Zuo et al., 2021). However, there is currently no existing literature on the variations in amino acid metabolic pathways between HPV-positive and HPV-negative HNSCC patients.

Given the characteristics of HPV infection and amino acid metabolism in HNSCC, identifying amino acid metabolism biomarkers associated with HPV infection is crucial for early diagnosis, treatment planning, and prognosis assessment. However, the complex relationship between HPV infection and amino acid metabolism reprogramming in HNSCC is not yet fully understood. Therefore, gaining a comprehensive understanding of the intricate interactions between amino acid metabolism and HPV infection will provide valuable insights into exploring the development of HNSCC and developing more effective treatments to improve patient survival. In this study, we employed bioinformatics methods to comprehensively analyze the relationship between HPV infection and amino acid metabolism patterns in large datasets, elucidating the connection between the two in HNSCC more explicitly. Additionally, we conducted further screening for prognostic biomarkers, thereby establishing a theoretical foundation for clinical translation.