High P16INK4A Expression, Keratinizing Features, and Surgical Margin-Free Status are Associated with Improved Survival in Patients with Oral Squamous Cell Carcinomas

Q: What is the study’s main focus regarding p16INK4A in OSCC?

The study evaluates p16INK4A expression in OSCC tissues and examines how it relates to recurrence risk and overall survival outcomes.

Q: What follow-up findings were reported for OSCC recurrences and mortality?

With a median follow-up of 32 months, recurrences and mortality were observed in 82% and 78% of patients, respectively (N=60).

Q: Which clinical factors were associated with improved prognosis in OSCC patients?

Better recurrence-free and overall survivals were associated with p16INK4A positive staining, early stages, non-keratinizing tumors, negative cervical node status, and free surgical margins.

Sep 21, 2026

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Oral squamous cell carcinoma (OSCC) remains a highly prevalent cancer in Southeast Asia, creating significant health burden due to recurrence and mortality. The study stratifies risk by analyzing p16 expression in formalin-fixed paraffin-embedded OSCC tissues and comparing clinicopathologic parameters to identify factors linked to recurrence and overall survival. After 32 months median follow-up, 82% recurrence and 78% mortality were observed. Larger tumors, p16 positivity, and favorable clinical features, including free surgical margins and negative cervical nodes, correlated with better outcomes.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages9

Reading Time23 min

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Abstract

Background

Methods

Results

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Materials and Methods

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RESEARCH ARTICLE Editorial Process: Submission:08/18/20 Acceptance:03/01/2024 High P16INK4A Expression, Keratinizing Features, and Surgical Margin-Free Status are Associated with Improved Survival in Patients with Oral Squamous Cell Carcinomas Sumadi Lukman Anwar1*, EryKus Dwianingsih2, SetyaniPuji Lestari2, William Sugandhi1, Roby Cahyono1, Gizza Dandy Pradana1 Abstract Background: Oral squamous cell carcinoma (OSCC) continues to prevail as a highly prevalent cancer in Southeast Asia and causes a significant health burden. Stratification of patients with high risks of recurrence and mortality is important in the planning of treatment and surveillance. Methods: Formalin-fixed paraffin-embedded (FFPE) tissues of OSCC were immuno-stained and analyzed for p16 expression. Risk factors and clinical parameters ofOSCC patients were collected and compared to identify factors associated with recurrences and overall survival. Results: After a median follow-up of 32 months, OSCC recurrences and mortality were observed in 82% and 78% of patients (N=60), respectively. Larger and more extensive tumors (T3 and T4) were significantly associated with both recurrences and cancer-associated mortality (OR = 3.967, 95% CI = 1.007-15.618 and OR = 5.885, 95% CI = 1.541-22.47, respectively) . P16INK4A positive staining was found in 31% of tumors. Patients with p16INK4A positive staining were significantly associated with better recurrence-free and overall survivals (medians of recurrence-free survivals were 31.2 vs 19.0 months, P=0.038 and overall survivals were 39.0 vs 28.8 months, P=0.048; respectively) . Some other clinical characteristics including early stages, non-keratinizing tumors, negative cervical node, and free-surgical margin were significantly associated with better recurrence-free and overall survivals (log-rank tests, P<0.05) . Conclusion: P16INK4A positive staining, early stages, negative cervical lymph node infiltration, and free-surgical margins are associated with better prognosis in OSCC patients. The study emphasizes the importance of early detection and the potential use of p16INK4A and other clinical variables to stratify OSCC patients with high risks of recurrence and worse overall survivals. Keywords: Squamous cell carcinoma-buccal and tongue-p16-prognosis Asian Pac J Cancer Prev, 25 (3), 857-865 Introduction Squamous cell carcinoma of the head and neck (HNSCC) is the sixth most common cancer worldwide, with relatively high recurrence and mortality rates [1] . There has been a significant improvement in the management of oral cancer with the introduction of multimodal treatment of surgery, concomitant chemotherapy-radiotherapy, the addition of taxanebased induction chemotherapy, and the emergence of some novel targeted therapies [2] . The high prevalence in South Asia and South East Asia has been associated with the consumption of specific substances of betel quid, tobacco products, and smokeless tobacco [3, 4]. Smoking and alcohol consumption are two principal predisposing factors for oral squamous cell carcinomas (OSCCs) [4] . Tobacco use is a very common practice among Indonesian men yet alcohol isnot regularly consumed [5]. In addition, evidence shows that high-risk human papilloma virus (HPV) infection is involved in oral cancer [6] . Patients with chronic HPV infection often have specific biological mechanisms and clinical consequences [7] . P16 protein acts as a tumor suppressor and it is negatively regulated by protein retinoblastoma (pRB) [8] . In the presence of HPV infection, the virus can express viral oncoproteins, E6 and E7 [9, 8] . E6 protein can degrade p53 causing cell cycle arrest and induction of apoptosis [9] . E7 oncoprotein induces breakdown of retinoblastoma protein (pRb) that is involved in cell cycle regulation . Retinoblastoma protein is a negative regulator of p16 protein, therefore, depletion of pRb can cause p16 over-expression [9]. HPV-associated oral cancer is usually ac

FAQs

What is the study’s main focus regarding p16INK4A in OSCC?

The study evaluates p16INK4A expression in OSCC tissues and examines how it relates to recurrence risk and overall survival outcomes.

What follow-up findings were reported for OSCC recurrences and mortality?

With a median follow-up of 32 months, recurrences and mortality were observed in 82% and 78% of patients, respectively (N=60).

Which clinical factors were associated with improved prognosis in OSCC patients?

Better recurrence-free and overall survivals were associated with p16INK4A positive staining, early stages, non-keratinizing tumors, negative cervical node status, and free surgical margins.

Sep 21, 2026

Uploaded by Ivy