Dataset Information

Immunotherapy in HPV-Related Oropharyngeal Cancers.

ABSTRACT:

Opinion statement

Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) incidence has been increasing in recent decades. Treatment of the locally advanced HPV-related OPSCC includes a multidisciplinary approach. Immunotherapy with immune checkpoint inhibitors is used in the treatment of patients with recurrent/metastatic head and neck squamous cell carcinomas (HNSCC), including HPV-related OPSCC patients. There is increasing knowledge of the role of HPV in the tumor immune microenvironment. Therefore, HPV status of OPSCC plays an essential role in the design of immunotherapy clinical trials in both curative intent and metastatic settings. Moreover, HPV has become a potential therapeutic target, with vaccines and adoptive T-cell therapies being developed against HPV for the treatment of OPSCC. Several novel studies are designed to target HPV in combination with immune checkpoint inhibitors. Thus, HPV-related OPSCC remains a unique subgroup in the immunotherapy era.

SUBMITTER: Roof L

PROVIDER: S-EPMC9887557 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Immunotherapy in HPV-Related Oropharyngeal Cancers.

Roof Logan L Yilmaz Emrullah E

Current treatment options in oncology 20230131 3

<h4>Opinion statement</h4>Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) incidence has been increasing in recent decades. Treatment of the locally advanced HPV-related OPSCC includes a multidisciplinary approach. Immunotherapy with immune checkpoint inhibitors is used in the treatment of patients with recurrent/metastatic head and neck squamous cell carcinomas (HNSCC), including HPV-related OPSCC patients. There is increasing knowledge of the role of HPV in the ...[more]

PMID: 36719604

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Project description:Head and neck cancer (HNC) is the fifth most common malignancy worldwide with an annual mortality rate of 200,000. About 90% of HNC can be classified as head and neck squamous cell carcinomas (HNSCC), of which approximately 75% are attributed to alcohol and tobacco consumption and 25 are associated with human papillomavirus (HPV), predominantly HPV16. HPV-associated OPC have better prognosis and a more favorable response to therapy as compared to HPV-negative tumors. Viral oncoproteins are capable of transforming primary human keratinocytes from either genital or oral epithelia in vitro and most likely play the same role in vivo, by disrupting cell-cycle regulatory pathways leading to a genetic progression to ano-genital cancer and OPC. However, the precise mechanisms by which HPV mediates malignant transformation of keratinocytes in the upper digestive tract epithelia are not entirely clear. HPV E7-mediated inactivation of pRb results in overexpression of p16INK4A, which is commonly used as a clinical surrogate marker for HPV positivity/activity. However, high p16INK4A alone has insufficient sensitivity and specificity as a biomarker of HPV positivity in different mucosal sub-sites of HNC. Therefore, increasing emphasis is being placed on the assessment of viral load and E7 oncogene expression, resulting in further classification of HPV positive OPC as HPV-active and HPV-inactive. Differences in risk factors, age of presentation, clinical behavior and gene expression profiles indicate that HPV-positive and HPV-negative tumors develop via different molecular mechanisms and are biologically distinct. This study aimed to compare the gene expression profiles of HPV-negative and HPV-inactive OPCs from both African American and European American patients, and determine their biological and racial differences. ANALYSIS 4: Four-condition, one-color experiment: African American (AA) HPV-inactive, African American (AA) HPV-negative, European American (EA) HPV-inactive, European American (EA) HPV-negative oropharyngeal tumor samples. Biological replicates: 4 AA HPV Inactive samples, 8 AA HPV Negative samples, 4 EA HPV Inactive samples and 8 EA HPV Negative samples,

Project description:BackgroundHerein, we evaluated the attributable fraction (AF) of human papillomavirus (HPV)-mediated (HPV+) oropharyngeal carcinomas (OPCs) in Greece over a recent calendar period.Patients and methodsORPHEAS, a retrospective, observational, multicenter, cross-sectional study with prospective recruitment, included adult patients with OPC in 2017-2022, each of them with a high-quality, treatment-naïve tumor specimen. The primary endpoint was the HPV-AF, defined as combined positivity for p16INK4a (p16) overexpression and HPV DNA presence by central laboratory testing, among included patients. Other endpoints evaluated the HPV+/HPV- patient/disease characteristics at OPC diagnosis and the HPV subtypes for HPV+ patients.Results144/147 patients with available HPV status by central laboratory testing were analyzed [median age: 60.0 years; males: 111 (77.1%)]. The most common tumor anatomical sites were the tonsils (70/147, 48.6%) and the base of the tongue (51, 35.4%), and most patients were at the American Joint Committee on Cancer eighth edition TNM (tumor-node-metastasis) stages III (25, 22.7%) and IV (43, 39.1%). The HPV-AF was 52.1% (75/144; 95% confidence interval 43.6% to 60.5%). Most HPV+ patients were infected by an HPV type targeted by the 9-valent HPV vaccine (72/75, 96.0%), especially HPV16 (70/75, 93.3%). HPV+ compared with HPV- patients were younger (median age 58.0 versus 64.0 years; P = 0.003); more likely to have tumors in the tonsils (65.0% versus 30.4%; P < 0.001); less likely to have tumors in the base of the tongue (25.3% versus 46.4%; P = 0.008); and less frequently at TNM stage IV (20.4% versus 57.1%; overall P < 0.001).ConclusionsIn Greece, we observed a high HPV-AF (52.1%) in OPC, approximating the AFs reported for some Northern European countries. HPV+ versus HPV- patients were younger, more frequently with tonsillar tumors, and less frequently at TNM stage IV. Since most patients were infected by ≥1 HPV type targeted by the 9-valent vaccine, the HPV+ OPC burden could be mitigated through a routine HPV gender-neutral vaccination program.

Dataset Information

Immunotherapy in HPV-Related Oropharyngeal Cancers.

Opinion statement

Publications

Immunotherapy in HPV-Related Oropharyngeal Cancers.

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