The tumor immune microenvironments of HPV⁺ and HPV⁻ head and neck cancers

Abstract

Human papillomaviruses (HPVs) are the etiological agent of a significant, and increasing, fraction of head and neck squamous cell carcinomas (HNSCC)-a heterogenous group of malignancies in the head and neck region. HPV infection accounts for approximately 25% of all cases, with the remainder typically caused by smoking and excessive alcohol consumption. These distinct etiologies lead to profound clinical and immunological differences between HPVpositive (HPV + ) and HPV-negative (HPV À ) HNSCC, likely related to the expression of exogenous viral antigens in the HPV + subtype. Specifically, HPV + HNSCC patients generally exhibit better treatment response compared to those with HPV À disease, leading to a more favorable prognosis, with lower recurrence rate, and longer overall survival time. Importantly, a plethora of studies have illustrated that the tumor immune microenvironment (TIME) of HPV + HNSCC has a strikingly distinct immune composition to that of its HPV À counterpart. The HPV + TIME is characterized as being immunologically "hot," with more immune infiltration, higher levels of T-cell activation, and higher levels of immunoregulation compared to the more immunologically "cold" HPV À TIME. In general, cancers with an immune "hot" TIME exhibit better treatment response and superior clinical outcomes in comparison to their immune "cold" counterparts. Indeed, this phenomenon has also been observed in HPV + HNSCC patients, highlighting the critical role of the TIME in influencing prognosis, and further validating the use of cancer therapies that capitalize on the mobilization and/or modulation of the TIME.

Efficacy of immune checkpoint inhibitors differs in various status of carcinoma: a study based on 29 cohorts with 3255 participants

“…In contrast, the immune-inflamed phenotype, referred to as "hot tumors", exhibited a significantly stronger response to ICIs [ 8 , 10 ]. Studies demonstrated that tumors associated viral infection often exhibit an “hot tumor” [ 11 , 12 ]. However, the impact of viral infection in tumors on the efficacy of ICIs remains a topic of debate in clinical practice, with no established consensus.…”

Identification of HPV oncogene and host cell differentiation associated cellular heterogeneity in cervical cancer via single‐cell transcriptomic analysis

“…[1][2][3] Specifically, persistent HPV infection in the host epithelium is one of the critical steps of cervical cancer development. 4,5 Current prophylactic HPV vaccines have enabled the prevention of initial infection and HPV-associated malignancies. However, HPV vaccination rates vary by state in the United States (from 31% to 79% of adolescents being HPV UTD [up-to-date]), certain high-risk HPV types are not covered in vaccines, and these vaccines will not eliminate viruses from infected individuals.…”

“…Human Papillomavirus (HPV) infection causes the most common sexually transmitted diseases and up to 5% of human cancer, including anogenital cancer, and head and neck cancer 1–3 . Specifically, persistent HPV infection in the host epithelium is one of the critical steps of cervical cancer development 4,5 . Current prophylactic HPV vaccines have enabled the prevention of initial infection and HPV‐associated malignancies.…”

HPV16 Intratypic Variants in Head and Neck Cancers: A North American Perspective

“…Viruses 2023, 15, 2411 2 of 18 HNCs are a heterogeneous group of malignancies in the head and neck region that includes the oral cavity, oropharynx, hypopharynx, and larynx [6,10,11]. It is the 7th most diagnosed cancer worldwide, with approximately 890,000 new cases and 453,000 deaths in 2018 [5].…”

“…HR HPVs are responsible for approximately 25% of all HNCs, with 83% of the HPV-positive (HPV + ) subtype being caused by HR HPV16 [10,12]. In comparison to the HPV-negative (HPV − ) subtype-caused by excessive drinking and smoking-HPV + HNCs are a distinct epidemiological, molecular, and clinical entity with patients exhibiting strikingly better responses to treatment and clinical outcomes [10,11,[13][14][15][16][17]. Interestingly, HNCs caused by other HR HPVs other than HPV16 have been associated with different patient outcomes [18][19][20].…”