Immunohistochemical analysis of p16 expression, HPV infection and its prognostic utility in oral squamous cell carcinoma

ObjectiveOur goal was to analyze the demographic and pathologic characteristics as well as prognosis in nonsmoking and nondrinking (NSND) oral squamous cell carcinoma (SCC) patients compared with typical oral SCC patients.Patients and MethodsA total of 353 patients were retrospectively enrolled and divided into two groups: the NSND group and the current smoking/current drinking (CSCD) group. Demographic, pathologic, and molecular data were compared between the two groups. The main research endpoints were locoregional control (LRC) and disease-specific survival (DSS).ResultsIn the NSND group, 16.3%, 41.9%, and 53.5% of patients were aged no more than 40 years, were female, and had an educational background of high school or above compared to 3.7%, 6.0%, and 38.2% of patients in the CSCD group, respectively. A total of 15.1% of the NSND patients had SCC of the lower gingiva and floor of the mouth, which was lower than the 35.6% of patients in the CSCD group. CSCD patients were likely to have an advanced disease stage (48.7% vs 32.5%, p=0.042) and poorly differentiated cancer (26.6% vs 16.3%, p=0.042). The NSND patients had a mean Ki-67 index of 24.5%, which was lower than the mean of 35.7% in the CSCD patients. The two groups had no HPV infection and similar p16 expression (4.7% vs 10.1%, p=0.132), but there was higher expression of p53 (38.6% vs 17.4%, p<0.001) and p63 (59.9% vs 29.1%, p<0.001) in the CSCD group. The 5-year LRC rates for NSND patients and CSCD patients were 48% and 38%, respectively, and the difference was significant (p=0.048). The 5-year DSS rates for NSND patients and CSCD patients were 56% and 39%, respectively, and the difference was significant (p=0.047). Further, a Cox model confirmed the independence of smoking and drinking status for affecting LRC and DSS.ConclusionNSND oral SCC patients are a different entity. HPV infection has a limited role in carcinogenesis in NSND patients, and p16 expression is associated with worse locoregional control.

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Features and prognostic utility of biopsy in oral squamous cell carcinoma

Head & Neck ◽

10.1002/hed.24335 ◽

2015 ◽

Vol 38 (S1) ◽

pp. E1857-E1862 ◽

Cited By ~ 7

Author(s):

Jagtar Dhanda ◽

Nugdeep Uppal ◽

Harpreet Chowlia ◽

Neil Opie ◽

Laith Al-Qamachi ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Prognostic Utility

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Heterozygosity of p16 expression in an oral squamous cell carcinoma with associated loss of heterozygosity and copy number alterations

Head & Neck ◽

10.1002/hed.25566 ◽

2018 ◽

Vol 41 (5) ◽

pp. E62-E65 ◽

Cited By ~ 1

Author(s):

Melvin A. Ambele ◽

Michael S. Pepper ◽

Marlene B. Heerden ◽

Willie F. P. Heerden

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Loss Of Heterozygosity ◽

Squamous Cell ◽

Copy Number ◽

Copy Number Alterations ◽

P16 Expression

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Assesment and clinicopathological correlation of P16 expression in oral squamous cell carcinoma

International Journal of Clinical and Diagnostic Pathology ◽

10.33545/pathol.2020.v3.i4a.303 ◽

2020 ◽

Vol 3 (4) ◽

pp. 01-06

Author(s):

Patle Goldy ◽

Kudrimoti Jyoti ◽

Nakate Leena

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Clinicopathological Correlation ◽

P16 Expression

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Immunohistochemical analysis of angiogenesis by CD34 and mast cells by toluidine blue in different grades of oral squamous cell carcinoma

Journal of Oral and Maxillofacial Pathology ◽

10.4103/0973-029x.190950 ◽

2016 ◽

Vol 20 (3) ◽

pp. 467 ◽

Cited By ~ 7

Author(s):

PramodSangamesh Ingaleshwar ◽

Siddharth Pandit ◽

Dinkar Desai ◽

CPramod Redder ◽

AkhilS Shetty ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Mast Cells ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Toluidine Blue ◽

Immunohistochemical Analysis

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Association of DFNA5, SYK, and NELL1 variants along with HPV infection in oral cancer among the prolonged tobacco-chewers

Tumor Biology ◽

10.1177/1010428318793023 ◽

2018 ◽

Vol 40 (8) ◽

pp. 101042831879302 ◽

Cited By ~ 3

Author(s):

Sharbadeb Kundu ◽

Vijayalakshmi Ramshankar ◽

Akalesh Kumar Verma ◽

Soundara Viveka Thangaraj ◽

Arvind Krishnamurthy ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Genetic Susceptibility ◽

Squamous Cell ◽

Odds Ratio ◽

Mrna Decay ◽

Hpv Infection ◽

Nonsense Mediated Mrna Decay

Southeast Asia, especially India, is well known for the highest use of smokeless tobacco. These products are known to induce oral squamous cell carcinoma. However, not all long-term tobacco-chewers develop oral squamous cell carcinoma. In addition, germline variants play a crucial role in susceptibility, prognosis, development, and progression of the disease. These prompted us to study the genetic susceptibility to oral squamous cell carcinoma among the long-term tobacco-chewers. Here, we presented a retrospective study on prolonged tobacco-chewers of Northeast India to identify the potential protective or risk-associated germline variants in tobacco-related oral squamous cell carcinoma along with HPV infection. Targeted re-sequencing (n = 60) of 170 genetic regions from 75 genes was carried out in Ion-PGM™ and validation (n = 116) of the observed variants was done using Sequenom iPLEX MassARRAY™ platform followed by polymerase chain reaction–based HPV genotyping and p16-immunohistochemistry study. Subsequently, estimation of population structure, different statistical and in silico approaches were undertaken. We identified one nonsense-mediated mRNA decay transcript variant in the DFNA5 region (rs2237306), associated with Benzo(a)pyrene, as a protective factor (odds ratio = 0.33; p = 0.009) and four harmful (odds ratio > 2.5; p < 0.05) intronic variants, rs182361, rs290974, and rs169724 in SYK and rs1670661 in NELL1 region, involved in genetic susceptibility to tobacco- and HPV-mediated oral oncogenesis. Among the oral squamous cell carcinoma patients, 12.6% (11/87) were HPV positive, out of which 45.5% (5/11) were HPV16-infected, 27.3% (3/11) were HPV18-infected, and 27.3% (3/11) had an infection of both subtypes. Multifactor dimensionality reduction analysis showed that the interactions among HPV and NELL1 variant rs1670661 with age and gender augmented the risk of both non-tobacco- and tobacco-related oral squamous cell carcinoma, respectively. These suggest that HPV infection may be one of the important risk factors for oral squamous cell carcinoma in this population. Finally, we newly report a DFNA5 variant probably conferring protection via nonsense-mediated mRNA decay pathway against tobacco-related oral squamous cell carcinoma. Thus, the analytical approach used here can be useful in predicting the population-specific significant variants associated with oral squamous cell carcinoma in any heterogeneous population.

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