P53 Mutations and Human Papillomavirus Infection in Oral Squamous Cell Carcinomas: Correlation with Overall Survival (original) (raw)
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Journal of Oral Pathology & Medicine, 1997
We analyzed specimens of head and neck squamous cell carcinomas (HNSCC) from 110 patients for p53 gene mutations, and 92 of them for human papillomavirus (HPV) infection, in order to evaluate the prognostic significance of these factors by comparison with clinical follow‐up data. Mutations within the exons 5 to 8 of the p53 gene were found in 48 tumors (44%). Sequencing revealed in most cases mis‐sense mutations (16/21). Frequency of p53 gene mutations was not related to the tumor stage or the presence of lymph node metastases. Of the 46 tumors that were analyzed by immunohistochemistry. 26 stained positively (56%). The number of positively stained nuclei increased slightly with decreasing differentiation of the tumors, whereas no correlation was found between tumor stage and immunoreactivity. An infection with the high‐risk HPV types 16 and 18 could be detected in 39/92 tumor specimens (42%.). Follow‐up data were obtained from 99 patients within a range of 2 to 112 months. No depen...
The International Journal of Biological Markers, 2007
The aim of this study was to analyze the prognostic impact of mutated TP53 in patients with oral squamous cell carcinoma (OSCC) whose tumors were infected with human papillomavirus (HPV). Methods: Thirty-two HPV-positive OSCC patients were included. Most of them were clinically classified as stage III (n=29). All patients underwent postoperative radiotherapy (follow-up from 12 to 60 months, median 32). There were 21 relapses. DNA was isolated by phenol extraction from tumor tissue. HPV DNA (type 16, 18, 31, 33) was detected in genomic DNA of the tumors by the PCR-PAGE method. TP53 mutations (exons 4-8) were detected by the PCR-SSCP method. Results: A statistically significant difference in the number of relapses in HPV-infected (13/21) versus HPV-infected and TP53-mutated (8/8) patients was observed. Patients with both TP53 mutation and HPV infection had a significantly shorter disease-free interval than patients with HPV infection only (median 6 versus 31 months, respectively). Conclusions: TP53 mutations are associated with a higher risk of relapse and contribute to an even worse prognosis of patients with OSCC when the tumors are HPV infected. The shorter disease-free interval in patients with TP53 mutations indicates that the response to postoperative radiotherapy may be influenced by TP53 status. The presence of both HPV infection and TP53 mutations may define a particular group of tumors with a more aggressive phenotype in advanced OSCC.
Role of human papilloma virus in oral tongue squamous cell carcinoma
Asian Pacific Journal of Cancer Prevention Apjcp, 2011
Background: Human papilloma virus (HPV) is an important risk factor for head and neck cancer, specifically oropharyngeal cancer, but its association with oral tongue squamous cell carcinoma (SCC) is uncertain. The objectives were to determine the HPV16 prevalence in oral tongue SCCs, its integration status and to correlate the expression of oncogenic proteins with targets. Methods: In this case-control study with oral tongue SCC cases (n=60) and normal oral mucosa (n=46), HPV positivity was determined by polymerase chain reaction (PCR) using consensus and HPV 16 type specific primers and p16 immunohistochemistry (IHC). The viral integration status was determined with primers specific to the E2 gene and in situ hybridization (ISH). Immunohistochemical analysis of HPV oncogenic proteins (E6, E7) and their target proteins (p53, pRb, cyclinD1, p16, Notch-1, EGFR) proteins was carried out in HPV positive cases. The data was analyzed with SPSS software (v 11.0). Survival analysis was carried out by the Kaplan-Meier method. Results: HPV16 was detected in 48% (n=29) of the cases and none of the controls by PCR assay (p<0.001) while p16 IHC, as a surrogate HPV marker, detected 33% (n=18) of the cases; 18% (n=10) were detected by both the methods. Integration was observed in 83% (n=24) by E2-PCR and 67% (n=18) by ISH. The E6-p53 pathway was active in 33% of the cases; E7-pRb in 52% and both in 11%. HPV positivity was associated with well-differentiated cancers (p=0.041) and low recurrence rate (p=0.014). Conclusion: Our study confirms a positive correlation of HPV infection with oral tongue cancer.
Iranian Journal of Cancer Prevention, 2016
Background: Squamous cell carcinoma (SCC) is the most common malignancy of the oral cavity. A relationship between the human papilloma virus (HPV) infection and the prognosis of oral cavity SCC (OCSCC) has been discussed before. Objectives: We investigated the prevalence rate of HPV status in patients with OCSCC, and its effects on clinicopathological characteristics of tumors and patients' prognosis. Patients and Methods: Sections of formalin-fixed, paraffin-embedded tissue blocks from 114 histopathologically confirmed OCSCC cases were investigated in this study. Polymerase chain reaction (PCR) was applied to evaluate the HPV status in the samples. Results: Fifteen (13.16%) cases were identified as HPV positive. The detected viral subtypes in this study were the subtypes 6 and 11. The stage and especially lymph node stage was significantly higher in the HPV positive group compared to the HPV negative group (P = 0.04). Disease free survival (DFS) was remarkably lower in the HPV positive group compared to the HPV negative group (13.9 vs. 49.9 months, P = 0.02). Overall survival (OS) was also significantly inferior in the HPV positive group (15.7 vs. 49.6 months, P = 0.01). In the current study, no significant differences were observed between two groups in relation to the variables of age, gender, tumors site, tumor size, tumor grading and also the recurrence rate. Conclusions: The observed higher mortality rate among the HPV positive group indicates the poorer prognosis of this group in comparison with the HPV negative patients. The incidence rate of HPV infection was low in the studied samples; however, interaction of subtypes 6 and 11 of HPV in poorer prognosis of the patients and a carcinogenic role of HPV in OCSCC cannot be ruled out.
Open Medicine, 2012
Survival of patients with head and neck squamous cell carcinoma (HNSCC) is dependent on many factors-stage of the disease, treatment regimen, operation technique etc. Many authors discuss on association of survival with various biomarkers as HPV infection, p53 mutation and polymorphism or p16 expression. The objective of our study was to analyze the survival of HNSCC patients in association with HPV infection and p53 polymorphism. Methods. 39 patients with primary diagnosed HNSCC were investigated. HPV DNA was detected using PCR with general primers MY09/11; p53 polymorphism was analyzed using single nucleotide polymorphism assay by PCR. Results. Of the 39 patients, 12 (30.8%) had detectable HPV. After p53 polymorphism analysis heterozygous Prol/Arg type was found in 34 cases (87.2%). Survival was higher in laryngeal cancer patients and in patients when tumour was classified as T 1-2. Somewhat higher survival was in the HPV positive patients, however difference was not statistically significant (P = 0.7). Only significant factor influencing survival in our study group was site of primary tumour (P < 0.05). Conclusion. HNSCC patients' survival in our study depend on primary tumour site; HPV infection and p53 SNP was not associated with better survival.
Human papilloma virus: An etiological and prognostic factor for oral cancer?
Journal of investigative and clinical dentistry, 2018
The increasing prevalence of human papilloma virus (HPV)-positive oral tumors can be considered an epidemic. Although the incidence of HPV cervical cancer is decreasing, the incidence of oral cavity and oropharyngeal cancers associated with HPV is increasing. The presence of certain HPV genotypes could be a predictor of future oral cancer lesions, although lesions associated with HPV could be less aggressive and exhibit a higher survival rate. In the present study, we review the most important biologic, clinic, epidemiologic, and prognostic factors associated with HPV infection and oral cancer.
Oral Surgery, 2008
Aim: Cancer of the oral cavity is extremely prevalent in Pakistan. Human papillomavirus (HPV) has been shown to play a role in the development of oral squamous cell carcinoma (OSCC) and may even improve overall and disease-free survival. The purpose of this study was to determine prevalence and types of HPV in a high risk population and its correlation with overall and disease-free survival, chewing habits and histologic variables.Material and methods: A total of 140 patients of OSCC, having a long-term follow-up, were included in this study. HPV-general and type-specific 16 and 18 infection were investigated by means of polymerase chain reaction.Results: Out of 140 patients, HPV was detected in 95 (68%) patients, out of whom, 85 (90%) contained HPV16. HPV positive patients had comparatively prolonged overall survival when compared with HPV-negative patients, but this difference was not statistically significant (P = 0.97). HPV presence was also not found to correlate significantly with disease-free survival (P = 0.58). The male were significantly correlated [odds ratio (OR) = 2.34; 95% confidence interval (CI) = 1.13–4.84] with the HPV infection. Betel quid chewer were comparatively more prone to HPV positivity (OR = 2; 95% CI = 1.1–4.31).Conclusion: Our study found a high prevalence of HPV16 in OSCC of Pakistani patients with male sex showing significant correlation with HPV infection. However, we did not find a statistically significant favourable association between HPV, survival and histologic variables. Borderline significance of HPV positivity was also seen with betel quid chewing (P = 0.049).
Clinical Cancer Research, 2008
Purpose: Squamous cell carcinomas of the head and neck (HNSCC) often harbor p53 mutations, but p53 protein degradation by the viral oncoprotein E6 may supercede p53 mutations in human papillomavirus 16 (HPV16)^positive tumors. The prevalence of p53 mutations in HPV-positive HNSCCs is indeed lower, but in some tumors these alterations coexist. The purpose of this study was to discern whether HNSCCs differ in the type of p53 mutations as a function of HPV16 status. Experimental Design: The study was nested within a prospective multicenter study (ECOGE 4393/RTOG R9614) of patients with HNSCC treated surgically with curative intent. Tumors from one study center were used to construct a tissue microarray. The tumors were well characterized with respect to p53 mutational status. The tissue microarray was evaluated by HPV16 in situ hybridization. HPV16 analysis was also done on a select group of tonsillar carcinomas known to harbor disruptive p53 mutations defined as stop mutations or nonconservative mutations within the DNA binding domain. Results: HPV16 was detected in 12 of 89 (13%) HNSCCs. By tumor site, HPV16 was detected in 12 of 21 (57%) tumors from the palatine/lingual tonsils, but in none of 68 tumors from nontonsillar sites (P < 0.00001). Both HPV16-positive and HPV16-negative HNSCCs harbored p53 mutations (25% versus 52%), but disruptive mutations were only encountered in HPV16-negative carcinomas. Of seven tonsillar carcinomas with disruptive p53 mutations, none were HPV16 positive, in contrast to HPV16-positive tonsillar carcinomas without disruptive p53 mutations (0% versus 57%; P = 0.008). Conclusions: Although HPV16 and mutated p53 may coexist in a subset of HNSCCs, HPV16 and disruptive p53 mutations seem to be nonoverlapping events. A less calamitous genetic profile, including the absence of disruptive p53 mutations, may underlie the emerging clinical profile of HPV16-positive HNSCC such as improved patient outcome.
JNCI Journal of the …, 2003
Background: Human papillomavirus (HPV), the causal agent of cervical cancer, appears to be involved in the etiology of cancer of the oral cavity and oropharynx. To investigate these associations, we conducted a multicenter case-control study of cancer of the oral cavity and oropharynx in nine countries. Methods: We recruited 1670 case patients (1415 with cancer of the oral cavity and 255 with cancer of the oropharynx) and 1732 control subjects and obtained an interview, oral exfoliated cells, and blood from all participants and fresh biopsy specimens from case patients. HPV DNA was detected by polymerase chain reaction (PCR). Antibodies against HPV16 L1, E6, and E7 proteins in plasma were detected with enzyme-linked immunosorbent assays. Multivariable models were used for case-control and casecase comparisons. Results: HPV DNA was detected in biopsy specimens of 3.9% (95% confidence interval [CI] ؍ 2.5% to 5.3%) of 766 cancers of the oral cavity with valid PCR results and 18.3% (95% CI ؍ 12.0% to 24.7%) of 142 cancers of the oropharynx (oropharynx and tonsil combined) with valid PCR results. HPV DNA in cancer biopsy specimens was detected less frequently among tobacco smokers and paan chewers and more frequently among subjects who reported more than one sexual partner or who practiced oral sex. HPV16 DNA was found in 94.7% of HPV DNA-positive case patients. HPV DNA in exfoliated cells was not associated with cancer risk or with HPV DNA detection in biopsy specimens. Antibodies against HPV16 L1 were associated with risk for cancers of the oral cavity (odds ratio [OR] ؍ 1.5, 95% CI ؍ 1.1 to 2.1) and the oropharynx (OR ؍ 3.5, 95% CI ؍ 2.1 to 5.9). Antibodies against HPV16 E6 or E7 were also associated with risk for cancers of the oral cavity (OR ؍ 2.9, 95% CI ؍ 1.7 to 4.8) and the oropharynx (OR ؍ 9.2, 95% CI ؍ 4.8 to 17.7). Conclusions: HPV appears to play an etiologic role in many cancers of the oropharynx and possibly a small subgroup of cancers of the oral cavity. The most common HPV type in genital cancers (HPV16) was also the most common in these tumors. The mechanism of transmission of HPV to the oral cavity warrants further investigation. [J Natl Cancer Inst 2003;95: