CDKN2A negative

P=N/A, N=10, Active, not recruiting, Oslo University Hospital | Trial completion date: Dec 2024 --> Aug 2025

Tumors with p53 abnormal expression and absence of p16 showed a greater DOI. Our data suggest an association between PDL1 expression and increased inflammatory infiltrates in vulvar SCC.

SCC-CUPdef patients with positive vs. negative p16-status had significantly longer overall survival (53 vs. 41 Monate, p=0,037), as well as patients with cN1- vs. cN3-status and M0- vs. M1-status.p16-status influences diagnosis and therapy response in patients with SCC-CUP: in p16-positive SCC-CUPinit, primary tumor detection rates were significantly higher than in p16-negative SCC-CUPinit. In patients with SCC-CUPdef, p16-positivity was associated with improved overall survival, albeit to an extent which does not justify therapy de-escalation.

Syringocystadenocarcinoma papilliferum is an extremely rare tumor, with its occurrence in the perianal region being particularly uncommon. This case contributes to the limited literature on this malignancy, highlighting its clinical and pathological features.

The PI3K/AKT pathway regulates cell survival and apoptosis and is associated with the malignant transformation of oropharyngeal tumors. AKT expression in p16-negative tumors is a strong predictor of poor prognosis.

In high-risk HPV-positive CC patients, HPV seems to play a role in recurrent disease. Our findings support ongoing research on targeting HPV oncogenes in CC, also in metastatic disease.

A precise and accurate diagnosis is required in order to adequately stage and manage p16+ OPSCC, particularly with neck metastasis. The role of tobacco exposure and/or p53 mutations must be considered not only in p16+ OPSCC but especially in HPV-positive OPSCC. Until a more accurate diagnosis is possible, ENE should be considered even in p16+HPV+ OPSCC. Primary surgery with unilateral ND and bilateral tonsillectomy might be the treatment of choice given the numerous diagnostic and prognostic pitfalls. Therefore, it is inappropriate and risky to propose de-escalation protocols in routine clinical practice due to the risk of undertreatment.

P=N/A, N=180, Completed, Medical University of South Carolina | Active, not recruiting --> Completed | Trial completion date: Aug 2024 --> Jan 2024 | Trial primary completion date: Aug 2024 --> Dec 2023

A clonal rearrangement of the TRB gene was revealed in 6 out of 7 cases with 7q34 biallelic loss. Both biallelic deletions can be considered favorable prognostic factors, with an association with 9p21 being statistically significant (p = 0.01) and a trend for 7q34 (p = 0.12) being observed.

EGFR expression was found to be high in basal-non-p53 type and was further correlated with adverse prognostic indicators, lamina propria invasion, and high-grade cytology. The identification of molecular subtypes and EGFR expression through immunohistochemistry, alongside traditional bladder cancer classifications, enhances tumor behavior prediction and supports effective clinical management.

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.

The detection of HPV had a significant impact on survival probability for OPSCC patients with both p16-positive and p16-negative tumors. HPV testing should be integrated in cancer staging, especially in regions of low attributable fraction, alongside p16 evaluation to ensure a comprehensive assessment of prognosis.

P=N/A, N=150, Recruiting, University College, London | Phase classification: P2 --> P=N/A

P3, N=804, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed

There are two main patterns of P16 and P53 expression, P16-positive/P53 wild-type and P16-negative/P53-mutant, but no positive expression of both has been seen so far. It is worth noting that we reported the second case of PESCC with a history of breast cancer, where the patient had been taking the oral aromatase inhibitor drug (exemestane) for a long period of time to reduce the estrogen level, indicating the low estrogen level may be also a key factor in the pathogenesis of PESCC.

Systematic molecular profiling of these pts's tumors will improve our understanding in this rare entity. In a significant percentage of cases, it could provide the access to molecules targeting actionable MA.

Furthermore, the deletion of p16 significantly enhances the persistence of CD8+ T cells within tumors and suppresses the terminal exhaustion of tumor-infiltrating T cells. Overall, our findings elucidate how increased p16 expression reshapes T cell intracellular metabolism, drives T cell apoptosis and exhaustion differentiation, and ultimately impairs T cell anti-tumor function.

P1, N=42, Not yet recruiting, University of Chicago | Initiation date: Jan 2024 --> Jan 2025

P1, N=46, Suspended, University of Colorado, Denver | Phase classification: P1/2 --> P1

P1/2, N=46, Suspended, University of Colorado, Denver | Trial completion date: Nov 2025 --> Nov 2024 | Recruiting --> Suspended | Trial primary completion date: Nov 2024 --> Nov 2023

SPINK5, a known tumor suppressor gene in HNSCC, was already downregulated in low-grade dysplastic lesions, indicating an early deactivation in the evolution of the disease. Genomic alterations as well as aberrant immune gene expression can be observed early in the evolution of tumors of the upper aerodigestive tract, highlighting the potential for targeting early mechanisms of disease progression.

A pathway analysis of genes correlated with Th2 cells revealed the potential repression of the antitumor immune response and the activation of BRCA1-associated DNA damage repair in multiple cohorts. The Th2 infiltrates were enriched in the HPV/p16-negative HNSCC tumors and associated with LRR and mutations in CASP8, CREBBP/EP300, and pathways previously shown to impact the response to radiation.

The negative conization rate was 11.9%, with diagnostic errors identified across pre-surgical biopsy, cone specimen, and deeper levels. Risk factors included older age, higher parity, low expression of p16, Ki-67 and geminin (p<0.05). Recurrence represented 8.1% of the negative cones, without identification of statistically significant risk factors. Pathological review with deeper level sections and 2-year follow-up are recommended for patients with negative conizations.

The verrucous (warty) SCC subtype case was HPV6-positive and p16-negative. The presence of HPV16 and p16 overexpression in the examined tissue specimens lends additional support for the role of HPV in the etiology of scrotal SCC.

There is strong correlation between EGFR overexpression and M2 polarization in patients with p16-negative OPC. Immunotherapy with or without EGFR inhibitor could be considered in these high-risk patients.

P2, N=60, Recruiting, IO Biotech | N=30 --> 60

P2, N=180, Not yet recruiting, ECOG-ACRIN Cancer Research Group | Initiation date: Jan 2024 --> Apr 2024

The large amount of ascites decreased after the start of administration of fulvestrant and CDK4/6 inhibitor(PAL). Fifty months later, she continues to do good ADL and PR status. We experienced a case of metastatic breast cancer with massive ascites and peritoneal metastasis that was successfully treated with a CDK4/6 inhibitor(PAL)and achieved long- term survival.

To conclude, the mean viral load in HPVDNA+/p16+ OPSCC was higher than in HPVDNA+/p16- OPSCC, but there was no statistically significant difference in viral load depending on OPSCC subsite or on clinical outcome.

SPINK5, a known tumour suppressor gene in HNSCC, was already downregulated in low-grade dysplastic lesions, indicating an early deactivation in the evolution of the disease. Genomic alterations as well as aberrant immune gene expression can be observed early on in the evolution of tumours of the upper aerodigestive tract, highlighting the potential for targeting early mechanisms of disease progression.

Our study revealed that CDKN2A LOF NSCLC patients treated with immune checkpoint inhibitor (ICI) mono-therapy or combined therapy had a worse prognosis than those with CDKN2A wild-type NSCLC. However, our study also suggested that ICI could work quite effectively in selective CDKN2A LOF patients.

In the patients with T3 & T4a EACSCC, prognosis of the patients with positive p16 expression EACSCC tended to be better than those with negative p16 expression. These results suggest the clinical significance of EGFR and p16 expressions in the patients with advanced EACSCC to predict oncological outcomes.

P2, N=30, Recruiting, IO Biotech | Trial completion date: Aug 2028 --> Jan 2027 | Trial primary completion date: Sep 2025 --> Apr 2025

1. Ours is the first study to demonstrate that SP263 and E3L1N can reliably be used to evaluate PD-L1 in PCs as there is good concordance with the reference clone 22C3. 2.

P=N/A, N=420, Recruiting, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano | Trial completion date: Jan 2025 --> Jun 2025 | Trial primary completion date: Apr 2024 --> Sep 2024

P2, N=45, Recruiting, UNC Lineberger Comprehensive Cancer Center | Trial completion date: Oct 2025 --> Oct 2026 | Trial primary completion date: Oct 2024 --> Oct 2025

The P value was not significant when p16 positivity with other parameters. HPV-associated were 90%, HPV-independent were 10%.

Tumor volume, p16, and CSC markers are potential biomarkers for HDF for patients with HNSCC treated with (C-)RT. Lower expression of CSC in p16+ OPSCC may contribute to better tumor control.

P1, N=42, Not yet recruiting, University of Chicago | Trial primary completion date: Nov 2025 --> Oct 2027

P2, N=97, Recruiting, University Medical Center Groningen | Not yet recruiting --> Recruiting

P2, N=0, Withdrawn, Replimune Inc. | N=130 --> 0 | Not yet recruiting --> Withdrawn

P=N/A, N=100, Completed, Tata Medical Center | Recruiting --> Completed | Phase classification: P1/2 --> PN/A