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Background:
Recent epidemiological data have implicated human papilloma virus (HPV) infection in the pathogenesis of head and neck cancers, especially oropharyngeal cancers. Although, HPV has been detected in varied amounts in persons with oral dysplasia, leukoplakias and malignancies, its involvement in oral tongue carcinogenesis remains ambiguou...
Contexts in source publication
Context 1
... rest of the samples were tested for presence of HPV DNA by PCR using two sets of primers. The sequences for the SPF10 and GP5+/GP6+ primers are shown in (Table 1) (Snijders et al., 1990). The PCR reaction mixture of 25 µl included 1XPCR buffer, 2.5 mM MgCl 2 , 0.2 mM of each dNTP, 40 pmoles of each primer, 0.5 µg/µl BSA, 1U Taq DNA polymerase and 100ng of genomic DNA. ...
Context 2
... PCR to detect HPV 16 physical status: A TaqMan-based 5' exonuclease quantitative real-time PCR assay was used to determine the ratio of HPV16 E2 and E6 open reading frames (ORF) as described previously ( Lee et al., 2010). Briefly, primers and probes specific for the E2 ORF and E6 ORF of HPV16 were used in the assay (Table 1). The 76-bp product of the E2 primers is part of the hinge region of the HPV16 E2 ORF, which is deleted during the viral integration process. ...
Citations
... The studies are conducted across multiple states and regions of India, representing a broad geographic distribution, and include participants across different age groups, offering insights into age-related variations in HPV prevalence. The proportion of male Multiple studies were conducted in South India [43,44], Haryana [45][46][47], and Tamil Nadu [48,49]. Single studies were conducted in several other locations: Andhra Pradesh [50], Kerala [51], Kolkata [52], Mumbai [53,54], Karnataka [55,56], Chandigarh [57,58], and Assam [59,60]. ...
Background
Human papillomavirus (HPV) is increasingly recognized as a significant risk factor in the development of head and neck cancers (HNCs), with varying prevalence and impact. This study aims to systematically review and analyze the prevalence of HPV in HNCs in India, providing insights into regional variations.
Methods
A comprehensive literature search was carried out using PubMed, Embase, and Web of Science up to November 10, 2023. Inclusion criteria focused on original research reporting HPV-positive cases among HNC patients in India. We used Nested-Knowledge software, for screening, and data extraction. The modified Newcastle-Ottawa Scale was used for quality assessment of included studies. We pooled the prevalence of HPV among HNC patients and performed a random-effects model meta-analysis using R software (version 4.3).
Results
The search yielded 33 studies, encompassing 4654 HNC patients. The pooled prevalence of HPV infection was found to be 33% (95% CI: 25.8–42.6), with notable heterogeneity (I² = 95%). Analysis of subgroups according to geographical location indicated varying prevalence rates. Specifically, the prevalence was 47% (95% CI: 32.2–62.4) in the eastern regions and 19.8% (95% CI: 10.8–33.4) in the western regions. No evidence of publication bias was detected.
Conclusion
The observed considerable regional disparities on the prevalence of HPV in HNC patients in India emphasizes the need for integrated HPV vaccination and screening programs in public health strategies. The findings underline the necessity for further research to explore regional variations and treatment responses in HPV-associated HNCs, considering the impact of factors such as tobacco use and the potential benefits of HPV vaccination.
... 19 Although the incidence of HPV-associated OPC appears to be highest in high-income countries, more epidemiologic data are needed from lowand middle-income countries. Most of the global data on 47 Bandhary et al 24 Bhattacharya et al 48 Bhosale et al 32 Bijina et al 49 Chaudhary et al 50 Dalakoti et al 51 Elango et al 52 Gheit et al 53 Gholap et al 54 Gupta et al 25 Kundu et al 55 Koppikar et al 26 Kulkarni et al 56 Laprise C et al 57 Maitra et al 58 Mitra et al 59 Mondal et al 60 Pal et al 61 Palve et al 40 Patel et al 62 Rajesh et al 63 Ramshankar et al 41 Rathore et al 64 Sannigrahi et al 65 Sarmah et al 66 Singh et al 27 20 Among the two studies on LC, only a single study reporting a prevalence of 13.3% was taken for analysis as it fulfills the eligibility criteria. 21 The differences in the proportion between the sites indicate that HPV has a varying degree of pathogenicity in these anatomic sites. ...
... At the same time, it was overexpressed in some HPV-negative tumors, suggesting that the p16 levels might not indicate active HPV status. 41 Another study has shown that p16 expression in OC was associated with a higher tumor grade with 21.4% overexpression; however, none of the p16-positive tumors were associated with HPV. 42 Studies with only p16INK4a as an HPV detection method in HNC were not included, as many studies have found discordance between p16 and HPV positivity. ...
PURPOSE
Head and neck cancer accounts for about one third of the global burden in India. Mucosal high-risk human papillomavirus (HPV) has been hypothesized as a contributory risk factor for head and neck cancer (HNC) but its prevalence in Indian patients is not well established. Therefore, this systematic review and meta-analysis aimed to estimate the prevalence of HPV in HNC in India and their attributable fraction by considering the biomarkers of carcinogenesis, p16, and HPV E6/E7 mRNA.
METHODS
A systematic literature search was done in Medline via PubMed, Embase, Scopus, ScienceDirect, ProQuest, and Cochrane to identify studies on HPV and HNC in the Indian population, published between January 1990 and October 2022. Fifty-four eligible studies were identified and relevant clinical information was collected. Meta-analysis was conducted to estimate the pooled prevalence of HPV DNA, p16INK4a, and E6/E7 mRNA percent positivity by random-effect logistic regression model using Metapreg, STATA 18.
RESULTS
Thirty-four high-quality studies were taken for meta-analysis. The pooled prevalence of HPV in HNC was 20% (95% CI, 12 to 32) with a high level of heterogeneity ( I ² = 90.79%). The proportion of HPV in oropharyngeal cancer (OPC; 22% [95% CI, 13 to 34]) and laryngeal cancer (LC; 29% [95% CI, 17 to 46]) was higher than in oral cancer (OC; 16% [95% CI, 8 to 30]). The HPV-attributable fraction of OPC, considering the E6/E7 mRNA and p16 positivity, was 12.54% and 9.68%, respectively, almost similar to LC (11.6% and 9.57%), while it was much lower in OC (3.36% and 4%).
CONCLUSION
The HPV-attributable fraction is considerably lower for OC, suggesting a negligible causative role of HPV in OC. A significant proportion of OPC and LC are attributed to HPV; however, their exact causative role is unclear because of the presence of other known risk factors.
... p16 positivity was determined to be 68% and 52% in the studies by Gonzales-Moles et al. [13] and Ramshankar et al. [14] According to studies by Balaram et al.(1995) [15] and Rali M et al. (2016) [16], high-grade cervical lesions have a high proportion of cancer cells, which is associated with histological grades. ...
Background and Aim: In this study, the prevalence of head and neck squamous cell carcinoma (HNSCC) is examined, as well as any potential associations between it and factors like HPV infection, tobacco usage, and alcohol intake. The purpose of the study is to determine whether the expression of p53 and p16 in these tumors correlate with one another. Material and Methods: This is a cross-sectional retrospective study. In this study, it is being investigated if head and neck squamous cell carcinoma specimens can be used to detect the presence of p53 and p16 proteins using immunohistochemistry. In the investigation, 50 samples from June 2019 to May 2021 were evaluated. The chi-square test was used to assess the percentage of p53 and p16 staining for squamous cell carcinoma of the head and neck region. A value of <0.05 was regarded as statistically significant. Results: According to the study, the male-to-female ratio is 1.5:1. 80% of the patients had cancers in their mouths, with 10% having tumors in their oropharynx. 18% also smoked while they were drinking, joined by 52% who had a history of smoking. It was seen that 68% of them had well-differentiated carcinomas. However, higher-grade tumors had higher levels of p53 and p16 expression (p<0.05). Conclusion: Our research has found that high levels of p53 and p16 are present in patients with head and neck squamous cell carcinomas and that a relationship between these markers and tumor grade exists. This information might be useful in the early detection and treatment of head and neck squamous cell carcinoma.
... [35] In the present study, the p16 was used to determine the HPV in OSCC. Furthermore, 30% of the OSCC samples had p16-poitive cells, which in studies of Li et al., [29] 12.6%, Zito Marino et al. [36] 18.4%, Sabu et al. [37] 20.58%, Broccolo et al. [38] 9.1%, Wang et al. [39] 9.5%, Götz et al. [40] 94/5%, Sgaramella et al. [41] 33%, Fonmarty et al. [42] 7/43%, Patil et al. [21] 66/86%, Ramshankar et al. [43] 15.38%, Saghravanian et al. 13.16%, [44] and 10% in Tokuzen et al. study [45] reported positive lesions. These differences may be due to technical sensitivity in the IHC staining method. ...
Background:
Due to the increasing prevalence of oral squamous cell carcinoma (OSCC) in Iran and especially in young people, this study aimed to identify human papillomavirus (HPV) using p16 in OSCC.
Materials and methods:
In this descriptive-analytical cross-sectional study, 40 samples from the archives of the Pathology Department of Kashani Hospital were selected by a definitive diagnosis of OSCC with neck dissection. Demographic information including age, gender, location, and size of the lesion was obtained. Samples were divided into two groups based on lymph node (LN) metastasis. Immunohistochemical staining was performed for p16. Data were entered into SPSS 24 software and statistically analyzed by t-test, ANOVA, and Spearman nonparametric test. P <0.05 was statistically significant.
Results:
The mean age of patients was 59.7 ± 17.11 which in terms of age and gender there was no significant difference between the two groups including with and without cervical LN metastasis (P > 0.05). There was no significant difference between the two groups based on the grade of tumor, perninural invasion, tumor size and location (P > 0.05). The only significant difference between the two groups was based on lymphovascular invasion and disease stage (P < 0.05). The p16 expression also showed a significant difference between the two groups (P < 0.05).
Conclusion:
In OSCCs without cervical LN metastasis, a significant increase in p16 expression was observed compared to samples with cervical LNs metastasis. The presence of HPV was higher in samples with less LNs metastasis and possibly a better prognosis.
... While a great proportion of oropharyngeal squamous cell carcinomas (OPSCCs), especially tonsillar and tongue base carcinomas (TSCC/BOTSCC), appear to contain the HPV genome and evaluation of p16 gene expression has successfully been used for the estimation of prognosis and recurrence of the disease [191], some researchers propose the cautious use of p16 expression status for the diagnosis of HPV(+) HNSCCs in non-tonsillar, non-base of tongue oropharyngeal cancers [192]. In OSCCs such as oral tongue cancers, for example, HPV infection and p16 overexpression do not seem to coincide [193]. Other studies indicate that HPV infection in OSCCs does not affect the survival outcome of the disease [194] and that p16 overexpression may be the result of other pathways or cellular mechanisms and not the consequence of HPV infection [193]. ...
... In OSCCs such as oral tongue cancers, for example, HPV infection and p16 overexpression do not seem to coincide [193]. Other studies indicate that HPV infection in OSCCs does not affect the survival outcome of the disease [194] and that p16 overexpression may be the result of other pathways or cellular mechanisms and not the consequence of HPV infection [193]. However, additional large-scale studies need to be performed in order to draw conclusions on the diagnostic role of p16 expression in the different types of HNCs. ...
Head and neck cancer (HNC) is a term collectively used to describe a heterogeneous group of tumors that arise in the oral cavity, larynx, nasopharynx, oropharynx, and hypopharynx, and represents the sixth most common type of malignancy worldwide. Despite advances in multimodality treatment, the disease has a recurrence rate of around 50%, and the prognosis of metastatic patients remains poor. HNCs are characterized by a high degree of genomic instability, which involves a vicious circle of accumulating DNA damage, defective DNA damage repair (DDR), and replication stress. Nonetheless, the damage that is induced on tumor cells by chemo and radiotherapy relies on defective DDR processes for a successful response to treatment, and may play an important role in the development of novel and more effective therapies. This review summarizes the current knowledge on the genes and proteins that appear to be deregulated in DDR pathways, their implication in HNC pathogenesis, and the rationale behind targeting these genes and pathways for the development of new therapies. We give particular emphasis on the therapeutic targets that have shown promising results at the pre-clinical stage and on those that have so far been associated with a therapeutic advantage in the clinical setting.
... It is important to note that we were unable to perform ddPCR on all the tumor blocks due to biospecimen availability, which likely negatively influenced our ROC curve analyses; and increasing the number of samples is predicted to strengthen the sensitivity and specificity measures. We note that p16 is a prognostic marker in its own right, regardless of HPV status (26,39,79,(146)(147)(148)(149)(150)(151)(152), and our survival analyses did not correct for that. Therefore, these findings could be strengthened by expanding to a larger and more inclusive HNSCC patient cohort. ...
Over 70% of oropharyngeal head and neck squamous cell carcinoma (HNSC) cases in the United States are positive for human papillomavirus (HPV) yet biomarkers for stratifying oropharyngeal HNSC patient risk are limited. We used immunogenomics to identify differentially expressed genes in immune cells of HPV(+) and HPV(−) squamous carcinomas. Candidate genes were tested in clinical specimens using both qRT-PCR and IHC and validated by IHC using the Carolina Head and Neck Cancer Study tissue microarray of HNSC cases. We performed multiplex immunofluorescent staining to confirm expression within the immune cells of HPV(+) tumors, ROC curve analyses, and assessed survival outcomes. The neuronal gene Synaptogyrin-3 (SYNGR3) is robustly expressed in immune cells of HPV(+) squamous cancers. Multiplex immunostaining and single-cell RNA sequencing analyses confirmed SYNGR3 expression in T cells, but also unexpectedly in B cells of HPV(+) tumors. ROC curve analyses revealed that combining SYNGR3 and p16 provides more sensitivity and specificity for HPV detection compared with p16 IHC alone. Patients with SYNGR3-high HNSC have significantly better prognosis with 5-year OS and DSS rates of 60% and 71%, respectively. Moreover, combining p16 localization and SYNGR3 expression can further risk stratify HPV(+) patients such that high cytoplasmic, low nuclear p16 do significantly worse (HR, 8.6; P = 0.032) compared with patients with high cytoplasmic, high nuclear p16. SYNGR3 expression in T and B cells is associated with HPV status and enhanced survival outcomes of patients with HNSC.
Significance
These findings indicate that codetection of SYNGR3 in immune cells and p16 in tumor cells by IHC can more reliably identify the HPV(+) subgroup of patients with low-risk head and neck cancer that may be appropriate for clinical trials involving treatment deescalation.
... The present study evaluated p16 protein in tongue cancer and observed cytoplasmic and nuclear staining of p16 protein in 24% of tongue cancer patients. Many studies have noted p16 expression between 10% to 57% in oral cancer and oropharyngeal cancer [9][10][11][12][13]. P16 expression was also noted Oral Leukoplakias [14]. ...
Tongue squamous cell carcinoma is the second most prevalent anatomic site of oral cancer in India which is associated with use of tobacco in various forms. p16INK4A a tumor suppressor gene and found inactivated by many mechanisms in cancer. This study role of p16 protein expression in tongue cancer patients. In this retrospective study, a total of 50 tongue cancer patients were enrolled. P16 protein was evaluated by immunohistochemistry on formalin fixed paraffin embedded tongue tumor tissues. Further, p16 protein expression was correlated with clinicopathological parameters and disease status. In this study, p16 expression was noted in 24% of tumor tissue of tongue cancer patients. In relation to clinical parameters, a significant higher p16 expression was seen in tobacco habituated patients. In relation with pathological parameters, a trend of higher p16 expression was noted in patients with T1 tumor size and poorly differentiated tumors. In univariate survival analysis, patients with p16 expression showed a trend of better diseases free survival and overall survival than patients with p16 negative expression. In summary, p16 overexpression can be considered as good prognosticator in tongue cancer. It may induce cellular senescence and thereby slower the tongue cancer growth.
... Ethical approval Not applicable. The regions covered are New Delhi [53,51,28,54], Prayagraj, Uttar Pradesh [55], Kolkata, West Bengal [56][57][58], Cuttack, Odisha [59], Dharwad, Karnataka [60], Mangalore, Karnataka [61], Bangalore, Karnataka [21], Trivandrum, Kerala [19], Chennai, Tamil Nadu [62], Mumbai, Maharashtra [63], and Ahmedabad, Gujarat [72]. The detailed account of samples, specimen type, DNA isolation, and other important features of these studies is outlined in Supplementary Table ST1 ...
Incidence of human papillomavirus (HPV)-associated oral cancers is on the rise. However, epidemiological data of this subset of cancers are limited. Dental hospital poses a unique advantage in detection of HPV-positive oral malignancies. We assessed the utility of formalin-fixed paraffin-embedded (FFPE) tissues, which are readily available, for evaluation of high-risk HPV infection in oral cancer. For protocol standardization, we used 20 prospectively collected paired FFPE and fresh tissues of histopathologically confirmed oral cancer cases reported in Oral Medicine department of a dental hospital for comparative study. Only short PCRs (~ 200 bp) of DNA isolated using a modified xylene-free method displayed a concordant HPV result. For HPV analysis, we used additional 30 retrospectively collected FFPE tissues. DNA isolated from these specimens showed an overall 23.4% (11/47) HPV positivity with detection of HPV18. Comparison of HPV positivity from dental hospital FFPE specimens with overall HPV positivity of freshly collected oral cancer specimens (n = 55) from three cancer care hospitals of the same region showed notable difference (12.7%; 7/55). Further, cancer hospital specimens showed HPV16 positivity and displayed a characteristic difference in reported sub-sites and patient spectrum. Overall, using a xylene-free FFPE DNA isolation method clubbed with short amplicon PCR, we showed detection of HPV-positive oral cancer in dental hospitals.
... geographical regions of India. The regions covered are New Delhi (Gupta et al., 2018;Gupta et al., 2015;Mishra et al., 2006;Verma et al., 2017), Prayagraj, Uttar Pradesh (Chaudhary et al., 2010), Kolkata, West Bengal (Ghosh et al., 2009;Mitra et al., 2007;Pal et al., 2018), Cuttack, Odisha (Nagpal, Patnaik, and Das, 2002), Dharwad, Karnataka (Kulkarni et al., 2011), Mangalore, Karnataka (Bandhary et al., 2018), Bangalore, Karnataka (Dhanapal et al., 2015), Trivandrum, Kerala (Balaram et al., 1995), Chennai, Tamil Nadu (Ramshankar et al., 2014), Mumbai, Maharashtra (D'Costa et al., 1998), Ahmedabad, Gujrat (Patel et al., 2014). The detailed account of samples, specimen type, DNA isolation and other important features of these studies are outlined in Supplementary Table ST1. ...
Incidence of human papillomavirus (HPV)–associated oral cancers is on the rise. However, epidemiological data of this subset of cancers is limited. Dental hospital pose a unique advantage in detection of HPV-positive oral malignancies. We assessed the utility of formalin-fixed, paraffin-embedded (FFPE) tissues, which are readily available, for evaluation of high-risk HPV infection in oral cancer. For protocol standardization, we used 20 prospectively-collected, paired FFPE and fresh tissues of histopathologically-confirmed oral cancer cases reported in Oral Medicine department of a dental hospital for comparative study. Only short-PCRs (~200bp) of DNA isolated using a modified xylene-free method displayed a concordant HPV result. For HPV analysis, we used additional 30 retrospectively-collected FFPE tissues. DNA isolated from these specimens showed an overall 23.4% (11/47) HPV positivity with detection of HPV18. Comparison of HPV positivity from dental hospital FFPE-specimens with overall HPV positivity of freshly-collected oral cancer specimens (n-55) from three cancer care hospitals of the same region showed notable difference (12.7%; 7/55). Further, cancer hospital specimens showed HPV16 positivity and displayed a characteristic difference in reported sub-sites and patient spectrum. Overall, using a xylene-free FFPE-DNA isolation method clubbed with short amplicon PCR, we showed detection of HPV-positive oral cancer in dental hospitals.
... One study from the US employed formalin-fixed paraffin-embedded tissue (FFPE) samples archived between 1987-1995(Strome et al., 2002. Meanwhile, three studies from India and two studies from the US reported high-risk HPV DNA prevalence instead of overall HPV DNA prevalence (Bhosale et al., 2016;D'Souza et al., 2007;Elango et al., 2011;Ramshankar et al., 2014;Smith et al., 2004). In India, a vast heterogeneity ranging between 7.4% in Mumbai to 48% from Karnataka was observed in the high-risk HPV DNA prevalence estimate in tissue samples of oropharyngeal cancer cases among men (Bhosale et al., 2016;Elango et al., 2011;Kulkarni et al., 2011). ...
Prevalence of Human Papillomavirus (HPV) DNA among Men
with Oropharyngeal and Anogenital Cancers: A Systematic
Review and Meta-Analysis
