Evaluating the Feasibility of Nested PCR as a Screening Tool to Detect HPV Infection in Saliva of Oral Squamous Cell Carcinoma Subjects

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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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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P179 High risk HPV infection is associated with oral squamous cell carcinoma in Mexican patients: a case control study

Oral Oncology Supplement ◽

10.1016/s1744-7895(07)70456-x ◽

2007 ◽

Vol 2 (1) ◽

pp. 185

Author(s):

G. Anaya-Saavedra ◽

V.A. Ramírez-Amador ◽

M.E. Irigoyen-Camacho ◽

C.M. García-Cuellar ◽

A. García-Cuellar

Keyword(s):

Squamous Cell Carcinoma ◽

High Risk ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Case Control Study ◽

Hpv Infection ◽

Case Control ◽

High Risk Hpv ◽

Control Study

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Clinical significance of the G8 screening tool in elderly patients with oral squamous cell carcinoma

Clinical Oral Investigations ◽

10.1007/s00784-019-03056-y ◽

2019 ◽

Vol 24 (6) ◽

pp. 1953-1961 ◽

Cited By ~ 1

Author(s):

Shin-ichi Yamada ◽

Takumi Hasegawa ◽

Kohei Okuyama ◽

Nobuhiro Yamakawa ◽

Masaya Okura ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Elderly Patients ◽

Cell Carcinoma ◽

Clinical Significance ◽

Squamous Cell ◽

Screening Tool ◽

G8 Screening Tool

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Role of HPV-16 in Pathogenesis of Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma and Correlation of p16INK4A Expression in HPV-16 Positive Cases: An Immunohistochemical Study

ISRN Pathology ◽

10.1155/2013/807095 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 10

Author(s):

Gaurav Pralhad Agrawal ◽

Priya Shirish Joshi ◽

Anshita Agrawal

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Hpv Infection ◽

Hpv 16 ◽

Oral Epithelial Dysplasia ◽

Tissue Sections ◽

Oral Epithelial

The objective of current study is to evaluate the role of HPV-16 in the pathogenesis of oral epithelial dysplasias (OED) and oral squamous cell carcinoma (OSCC) by immunohistochemistry (IHC) and to know whether HPV-16 participates in disruption of the regulation of p16 INK4A suppressor protein in OED and OSCC by IHC. Histopathologically diagnosed 20 cases of OED and 20 cases of OSCC were selected from amongst the patients attending the OPD of Vasantdada Patil Dental College and Hospital, Sangli. Biopsy tissue section were then tested for HPV-16 by IHC. HPV-16 positive tissue sections were then again tested by p16 by IHC. Overall 22.5% of cases in our study were found to be positive for HPV 16 which includes 10% of cases of OED and 35% cases of OSCC. Amongst the HPV 16 positive cases, more than 60% of cells were positive for p16INK4A IHC in OED (50%) and OSCC (85.71%). Thus, HPV 16 participates in disruption of the regulation of p16INK4A suppressor protein and can be used as surrogate biomarker for detection of HPV infection in OED and OSCC.

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