Oropharyngeal Cancer

A combined score derived from TPS and ISS optimized recurrence prediction and stratified survival in a manner generalizable to three external cohorts. We provide novel evidence that limiting genomic instability makes tumor-intrinsic and immune-mediated contributions to HPV+ OPSCC recurrence risk, opening opportunities to detect and target this treatment-resistant biology.

P2, N=153, Not yet recruiting, Washington University School of Medicine

P=N/A, N=107, Completed, Helsinki University Central Hospital

Loco-regional treatments may also play a key role in the management of metastatic HPV OPSCC depending on the pattern of presentation. Our case series highlights all these novelties that could lead to better treatment outcomes.

P2, N=98, Not yet recruiting, NRG Oncology | Trial completion date: Sep 2026 --> Jan 2027 | Initiation date: Oct 2024 --> Apr 2025 | Trial primary completion date: Sep 2026 --> Jan 2027

Our study unveils the intricate interplay of ICMs in OPSCC, emphasizing the necessity for personalized therapeutic approaches based on HPV status and immune profiles. The identified ICMs, including PD1, CD27, and CTLA4, are promising candidates for further investigation and may enhance immunotherapeutic interventions in the HPV-dependent treatment strategies for OPSCC.

P3, N=500, Recruiting, Nanobiotix | Trial completion date: Jan 2026 --> Jun 2027 | Trial primary completion date: Jul 2024 --> Jun 2026

We concluded that the incidence of abnormal 53BP1 expression in OPSCC is significantly associated with stage classification and overall survival. Therefore, double IF analysis of 53BP1 and Ki-67 expression may be a useful tool for estimating the malignant potential and prognosis of OPSCC.

P=N/A, N=25, Not yet recruiting, Royal North Shore Hospital | Initiation date: Apr 2024 --> Nov 2024

P2, N=29, Recruiting, National Cancer Institute (NCI) | Trial completion date: Nov 2027 --> Nov 2028 | Trial primary completion date: Nov 2024 --> Nov 2025

P=N/A, N=120, Recruiting, AIO-Studien-gGmbH | Not yet recruiting --> Recruiting | Trial completion date: May 2030 --> Nov 2030 | Initiation date: May 2024 --> Nov 2024 | Trial primary completion date: May 2029 --> Nov 2029

P=N/A, N=60, Not yet recruiting, Virginia Commonwealth University

P2, N=77, Terminated, Regeneron Pharmaceuticals | Active, not recruiting --> Terminated; Sponsor Decision related to study drug supply

P=N/A, N=150, Active, not recruiting, Abramson Cancer Center at Penn Medicine | Trial completion date: Oct 2024 --> Jan 2025

A combined risk score incorporating clinical, nutritional, and immune factors can improve the prediction of treatment outcomes for OPC patients. This risk stratification may enable personalized treatment plans and improve ΟS rates.

It also serves as a biomarker for notable variations found in Firmicutes, Actinobacteria, Fusobacteriales, Fusobacteriia, Fusobacterium, and Fusobacteriaceae. Therefore, based on this we evidence, we could investigate the role of oral microbiota as a maker for the HPV associated HNSCC.

P2, N=123, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Oct 2024 --> Feb 2025

High xCT expression was associated with poor prognosis in OPSCC. Our findings suggest that joint analysis of xCT and p16 may add significant value in OPSCC treatment stratification.

P2, N=90, Recruiting, University of Virginia | Not yet recruiting --> Recruiting

P=N/A, N=118, Not yet recruiting, Emory University

P3, N=987, Active, not recruiting, Radiation Therapy Oncology Group

High TcellinfGEP status, but not PD-L1 or PD-L2 expression, was independently associated with longer survival in patients with LA HNSCC. Results may have implications for evaluating therapies targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) in HNSCC.

P2, N=24, Terminated, Regeneron Pharmaceuticals | Completed --> Terminated; Business Decision

P1, N=160, Terminated, Inhibrx Biosciences, Inc | Trial completion date: Dec 2025 --> Oct 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Aug 2025 --> Oct 2024; Program terminated due to lack of meaningful efficacy signal.

P2, N=37, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=180 --> 37

P2, N=24, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial primary completion date: Aug 2024 --> Apr 2025

The low-cost lateral flow immunochromatographic assay for detecting HPV16/18 E6 oncoproteins confirmed high accuracy for identifying HPV-associated OPSCC, particularly in primary tumors, suggesting its potential as a valuable diagnostic tool in clinical practice. Its rapid diagnostic capability could significantly accelerate the process of treatment decision-making, enhancing the timely management of patients.

P2, N=28, Not yet recruiting, Emory University

P=N/A, N=550, Recruiting, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

P2, N=76, Completed, University of Chicago | Active, not recruiting --> Completed

IGHM may be the key contributors to the prognostic differences in HPV-associated OPSCC. This nomogram model was able to accurately predict the prognosis of patients.

P3, N=117, Terminated, GlaxoSmithKline | Phase classification: P2/3 --> P3

P1/2, N=72, Recruiting, Theravectys S.A. | Not yet recruiting --> Recruiting | Initiation date: Mar 2024 --> Aug 2024

Compared to standalone p16, the combination of p16 overexpression and Rb-partial/complete loss showed equally excellent sensitivity and negative predictive value (each 100 %) as well as improved specificity (100 % versus 93.1 %) and positive predictive value (100 % versus 91.3 %). Our results suggest that combining p16 and Rb expression patterns may be helpful in screening for HR-HPV infection in metastatic lymph nodes and in estimating the primary site of SCC.

Integrating H&E and IHC data enhances the functional characterization of immune phenotypes of the TME with biological interpretability, and improves patient stratification in HPV( + ) OPSCC.

The association between PD-L1 positivity and HPV positivity (78.57%) was confirmed by meta-analysis. The conclusion was that HPV-positive status has an impact on immunohistochemical expression of PD-L1 in OPSCC.

P=N/A, N=180, Recruiting, Mayo Clinic | Trial completion date: Dec 2025 --> Nov 2029 | Trial primary completion date: Dec 2024 --> Nov 2029

P3, N=730, Terminated, EMD Serono Research & Development Institute, Inc. | Trial completion date: Apr 2027 --> Sep 2024 | Active, not recruiting --> Terminated; Study has crossed the pre-defined futility boundary at the Interim Analysis.

This study demonstrated for the first time a positive relationship between HPV presence and cIAP2 levels in OPCs. Additionally, cIAP2 knocking down sensitizes HNC cells to apoptosis promoted by radiation. Therefore, cIAP2 is a potential therapeutic target for radiation in HPV-driven HNC.

Indeed, INSM1 expression is more commonly observed in nonaggressive cancers. Reliance on INSM1 staining alone in recognizing NE differentiation in HPV-OPSCC could be calamitous.

In terms of immune-oncology-related gene expression, discordant p16+/HPV- OPCs are much more closely aligned with p16-/HPV-OPCs and quite distinct from p16+/HPV+ tumours. This is consistent with previously described prognostic patterns (p16+/HPV+ >> p16+/HPV- > p16-/HPV-) and underlines the need for dual p16 and HPV testing to guide clinical decision making.

P2, N=62, Completed, University of Chicago | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Sep 2024 | Trial primary completion date: Mar 2019 --> Sep 2024