Association of Salivary Human Papillomavirus Infection and Oral and Oropharyngeal Cancer: A Meta-Analysis

BACKGROUND: Human papillomavirus (HPV) infection has been recognized as an important risk factor in cancer. The purpose of this systematic review and meta-analysis was to determine the prevalence and effect size of association between salivary HPV DNA and the risk of developing oral and oropharyngeal cancer. METHODS: A systematic literature search of PubMed, EMBASE, Web of Science, LILACS, Scopus and the Cochrane Library was performed, without language restrictions or specified start date. Pooled data were analyzed by calculating odds ratios (ORs) and 95% confidence intervals (CIs). Quality assessment was performed using the Newcastle-Ottawa Scale (NOS). RESULTS: A total of 1672 studies were screened and 14 met inclusion criteria for the meta-analysis. The overall prevalence of salivary HPV DNA for oral and oropharyngeal carcinoma was 43.2%, and the prevalence of salivary HPV16 genotype was 27.5%. Pooled results showed a significant association between salivary HPV and oral and oropharyngeal cancer (OR = 4.94; 2.82-8.67), oral cancer (OR = 2.58; 1.67-3.99) and oropharyngeal cancer (OR = 17.71; 6.42-48.84). Significant associations were also found between salivary HPV16 and oral and oropharyngeal cancer (OR = 10.07; 3.65-27.82), oral cancer (OR = 2.95; 1.23-7.08) and oropharyngeal cancer (OR = 38.50; 22.43-66.07). CONCLUSIONS: Our meta-analysis demonstrated the association between salivary HPV infection and the incidence of oral and oropharyngeal cancer indicating its value as a predictive indicator

Interventions for the treatment of oral cavity and oropharyngeal cancer:chemotherapy

<b>Background:</b> Oral cavity and oropharyngeal cancers are frequently described as part of a group of oral cancers or head and neck cancer. Treatment of oral cavity cancer is generally surgery followed by radiotherapy, whereas oropharyngeal cancers, which are more likely to be advanced at the time of diagnosis, are managed with radiotherapy or chemoradiation. Surgery for oral cancers can be disfiguring and both surgery and radiotherapy have significant functional side effects, notably impaired ability to eat, drink and talk. The development of new chemotherapy agents, new combinations of agents and changes in the relative timing of surgery, radiotherapy, and chemotherapy treatments may potentially bring about increases in both survival and quality of life for this group of patients.<p></p> <b>Objectives:</b> To determine whether chemotherapy, in addition to radiotherapy and/or surgery for oral cavity and oropharyngeal cancer results in improved survival, disease free survival, progression free survival, locoregional control and reduced recurrence of disease. To determine which regimen and time of administration (induction, concomitant or adjuvant) is associated with better outcomes.<p></p> <b>Search strategy:</b> Electronic searches of the Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE, EMBASE, AMED were undertaken on 28th July 2010. Reference lists of recent reviews and included studies were also searched to identify further trials.<p></p> <b>Selection criteria:</b> Randomised controlled trials where more than 50% of participants had primary tumours in the oral cavity or oropharynx, and which compared the addition of chemotherapy to other treatments such as radiotherapy and/or surgery, or compared two or more chemotherapy regimens or modes of administration, were included.<p></p> <b>Data collection and analysis:</b> Trials which met the inclusion criteria were assessed for risk of bias using six domains: sequence generation, allocation concealment, blinding, completeness of outcome data, selective reporting and other possible sources of bias. Data were extracted using a specially designed form and entered into the characteristics of included studies table and the analysis sections of the review. The proportion of participants in each trial with oral cavity and oropharyngeal cancers are recorded in Additional Table 1.<p></p> <b>Main results:</b> There was no statistically significant improvement in overall survival associated with induction chemotherapy compared to locoregional treatment alone in 25 trials (hazard ratio (HR) of mortality 0.92, 95% confidence interval (CI) 0.84 to 1.00). Post-surgery adjuvant chemotherapy was associated with improved overall survival compared to surgery +/- radiotherapy alone in 10 trials (HR of mortality 0.88, 95% CI 0.79 to 0.99), and there was an additional benefit of adjuvant concomitant chemoradiotherapy compared to radiotherapy in 4 of these trials (HR of mortality 0.84, 95% CI 0.72 to 0.98). Concomitant chemoradiotherapy resulted in improved survival compared to radiotherapy alone in patients whose tumours were considered unresectable in 25 trials (HR of mortality 0.79, 95% CI 0.74 to 0.84). However, the additional toxicity attributable to chemotherapy in the combined regimens remains unquantified.<p></p> <b>Authors' conclusions:</b> Chemotherapy, in addition to radiotherapy and surgery, is associated with improved overall survival in patients with oral cavity and oropharyngeal cancers. Induction chemotherapy is associated with a 9% increase in survival and adjuvant concomitant chemoradiotherapy is associated with a 16% increase in overall survival following surgery. In patients with unresectable tumours, concomitant chemoradiotherapy showed a 22% benefit in overall survival compared with radiotherapy alone.<p></p&gt

Epidemiology of human papillomavirus-related oropharyngeal cancer in a classically low-burden region of southern Europe

The incidence of human papillomavirus (HPV)-related oropharyngeal cancer is increasing in some regions. Nevertheless, the epidemiology of this disease has not been extensively investigated in southern Europe. We conducted a retrospective cohort study of patients diagnosed with primary oropharyngeal cancer from 1991 to 2016. Cancer tissues underwent histopathological evaluation, DNA quality control, HPV-DNA detection and p16 immunohistochemistry. Data were collected from medical records. Factors associated with HPV positivity and time trends were evaluated with multivariable Bayesian models. The adjusted prevalence of HPV-related cases in 864 patients with a valid HPV-DNA result was 9.7%, with HPV-DNA/p16 double positivity being considered. HPV-related oropharyngeal cancer was likely to occur in non-smokers and non-drinkers, to be located in the tonsil or diagnosed at advanced stages. Time-trend analysis showed an increasing risk of HPV-related oropharyngeal cancer in the most recent periods (5-year period increase of 30%). This increase was highest and with a clear increasing trend only in the most recent years (2012-2016). The prevalence of HPV-related oropharyngeal cancer started to sharply increase in the most recent years in our setting, as occurred two decades ago in areas where most oropharyngeal cancer cases are currently HPV-related. Our results provide a comprehensive assessment of the epidemiological landscape of HPV-related oropharyngeal cancer in a region of southern Europe

Interventions for the treatment of oral and oropharyngeal cancers: surgical treatment.

BACKGROUND: Surgery is an important part of the management of oral cavity cancer with regard to both the removal of the primary tumour and removal of lymph nodes in the neck. Surgery is less frequently used in oropharyngeal cancer. Surgery alone may be treatment for early stage disease or surgery may be used in combination with radiotherapy, chemotherapy and immunotherapy/biotherapy. There is variation in the recommended timing and extent of surgery in the overall treatment regimens of people with these cancers. OBJECTIVES: To determine which surgical treatment modalities for oral cavity and oropharyngeal cancers result in increased overall survival, disease free survival, progression free survival and reduced recurrence. SEARCH STRATEGY: The following electronic databases were searched: the Cochrane Oral Health Group Trials Register (to 17 February 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1), MEDLINE via OVID (1950 to 17 February 2011) and EMBASE via OVID (1980 to 17 February 2011). There were no restrictions regarding language or date of publication. SELECTION CRITERIA: Randomised controlled trials where more than 50% of participants had primary tumours of the oral cavity or oropharynx, and which compared two or more surgical treatment modalities or surgery versus other treatment modalities. DATA COLLECTION AND ANALYSIS: Data extraction and assessment of risk of bias was undertaken independently by two or more review authors. Study authors were contacted for additional information as required. Adverse events data were collected from published trials. MAIN RESULTS: Seven trials (n = 669; 667 with cancers of the oral cavity) satisfied the inclusion criteria, but none were assessed as low risk of bias. Trials were grouped into three main comparisons. Four trials compared elective neck dissection (ND) with therapeutic neck dissection in patients with oral cavity cancer and clinically negative neck nodes, but differences in type of surgery and duration of follow-up made meta-analysis inappropriate. Three of these trials reported overall and disease free survival. One trial showed a benefit for elective supraomohyoid neck dissection compared to therapeutic ND in overall and disease free survival. Two trials found no difference between elective radical ND and therapeutic ND for the outcomes of overall survival and disease free survival. All four trials found reduced locoregional recurrence following elective ND.A further two trials compared elective radical ND with elective selective ND and found no difference in overall survival, disease free survival or recurrence. The final trial compared surgery plus radiotherapy to radiotherapy alone but data were unreliable because the trial stopped early and there were multiple protocol violations.None of the trials reported quality of life as an outcome. Two trials, evaluating different comparisons reported adverse effects of treatment. AUTHORS' CONCLUSIONS: Seven included trials evaluated neck dissection surgery in patients with oral cavity cancers. The review found weak evidence that elective neck dissection of clinically negative neck nodes at the time of removal of the primary tumour results in reduced locoregional recurrence, but there is insufficient evidence to conclude that elective neck dissection increases overall survival or disease free survival compared to therapeutic neck dissection. There is very weak evidence from one trial that elective supraomohyoid neck dissection may be associated with increased overall and disease free survival. There is no evidence that radical neck dissection increases overall survival compared to conservative neck dissection surgery. Reporting of adverse events in all trials was poor and it was not possible to compare the quality of life of patients undergoing different surgeries

EPIDEMIOLOGICAL STUDY ON HEAD AND NECK MALIGNANCIES - A STUDY OF 150 CASES

OBJECTIVE: In the present study we investigate the head and Neck Malignancy cases presenting to the ENT department of our Hospital, and analyze the same to give inputs as to the incidence of head and neck malignancies, the symptoms and stage of presentation, lifestyle and habits as contributory risk factors, identify ENT primary in neck secondaries, histopathological types and selection of best treatment.METHODS: Prospective analysis of 150 patients with newly diagnosed malignancies of nasopharynx, oropharynx, larynx, hypopharynx and ear.RESULTS: Most malignancies are common in patients greater than 40 years of age. 88% of cancer occur in males. Oropharynx cancer is the most common cancer in our study, with the commonest subsite as base of tongue. Supraglottic and pyriform fossa tumours are the commonest tumour in laryngeal and hypopharyngeal cancers  respectively. The most common presentation is dysphagia. Synergistic effect of smoking and alcohol is seen in 50% of patients. Most of the cases were seen in stage III and IV except glottis cancer which is predominantly seen in stage I, almost all cases were squamous cell carcinoma.CONCLUSION:The results of our study were in conformity with other similar studies. In larynx, Supraglottic was more common as opposed to glottis in certain western studies. Analysis of various factors helps in early diagnosis and management.KEYWORDS:Cancer, Head and Neck Malignancy, Larynx, pharynx, Nasopharynx, Neck secondaries.

Advances in the management of HPV-related oropharyngeal cancer

Patients with human papillomavirus- (HPV-) related oropharyngeal squamous cell carcinoma (OPSCC) have a better prognosis than HPV-negative OPSCC when treated with standard high-dose cisplatin-based chemoradiotherapy. Consistent with this assertion and due to younger age at diagnosis, novel approaches tominimize treatment sequelaewhile preserving survival outcomes become of paramount importance. Here, we critically reviewed the evidence-based literature supporting the deintensification strategies in HPV-related OPSCC management, including radiotherapy dose and/or volume reduction, replacement of cisplatin radiosensitising chemotherapy, and the use of transoral surgery. Undoubtedly, further researches are needed before changing the standard of care in this setting of patients

Oropharyngeal cancer mortality according to the human development index in the Metropolitan Region of Chile, 2002-2014

To determine mortality rates for oropharyngeal cancer according to the Human Development Index (HDI) per district in the Metropolitan Region (RM), Santiago, Chile, between 2002 and 2014. Materials and Methods: An ecological study was carried out. The sample corresponded to individuals over 45 years, from the Metropolitan Region, with oropharyngeal cancer as cause of death, as registered in the Chilean National Institute of Statistics (INE). The HDI was classified into three categories: “medium” (8 districts), “high” (18 districts) and “very high” (25 districts). The crude and adjusted mortality rates were calculated for each year and period. Results: The oropharyngeal cancer adjusted mortality rate for the chosen period was 3.98 deaths per 100,000 inhabitants. The specific mortality rate from oropharyngeal cancer in the “medium” HDI category was 4.01; in the “high”DHI category, 4.42; and in the “very high” HDI category, 3.79. Conclusion: Mortality from oropharyngeal cancer was higher in the “medium” HDI category between 2002 and 2014

Trends of oral cavity, oropharyngeal and laryngeal cancer incidence in Scotland (1975 - 2012) - a socioeconomic perspective

Aim: To examine current incidence trends (1975–2012) of oral cavity (OCC), oropharyngeal (OPC) and laryngeal cancer in Scotland by socioeconomic status (SES). Methods: We included all diagnosed cases of OCC (C00.3-C00.9, C02-C06 excluding C2.4), OPC (C01, C2.4, C09-C10, C14) and laryngeal cancer (C32) on the Scottish Cancer Registry (1975–2012) and annual midterm population estimates by age, sex, geographic region and SES indices (Carstairs 1991 and Scottish Index of Multiple Deprivation 2009). Age-standardized incidence rates were computed and adjusted Poisson regression rate-ratios (RR) compared subsites by age, sex, region, SES and year of diagnosis. Results: We found 28,217 individuals (19,755 males and 8462 females) diagnosed with head and neck cancer (HNC) over the study period. Between 1975 and 2012, relative to the least deprived areas, those living in the most deprived areas exhibited the highest RR (>double) of OCC, OPC and laryngeal cancer, and an almost dose-like response was observed between SES and HNC incidence. Between 2001 and 2012, this socioeconomic inequality tended to increase over time for OPC and laryngeal cancer but remained relatively unchanged for OCC. Incidence rates increased markedly for OPC, decreased for laryngeal cancer and remained stable for OCC, particularly in the last decade. Males exhibited significantly higher RRs compared to females, and the peak age of incidence of OPC was slightly lower than the other subsites. Conclusion: Contrary to reports that OPC exhibits an inverse socioeconomic profile, Scotland country-level data show that those from the most deprived areas consistently have the highest rates of head and neck cancers

Mutation signature analysis identifies increased mutation caused by tobacco smoke associated DNA adducts in larynx squamous cell carcinoma compared with oral cavity and oropharynx.

Squamous cell carcinomas of the head and neck (HNSCC) arise from mucosal keratinocytes of the upper aero-digestive tract. Despite a common cell of origin and similar driver-gene mutations which divert cell fate from differentiation to proliferation, HNSCC are considered a heterogeneous group of tumors categorized by site of origin within the aero-digestive mucosa, and the presence or absence of HPV infection. Tobacco use is a major driver of carcinogenesis in HNSCC and is a poor prognosticator that has previously been associated with poor immune cell infiltration and higher mutation numbers. Here, we study patterns of mutations in HNSCC that are derived from the specific nucleotide changes and their surrounding nucleotide context (also known as mutation signatures). We identify that mutations linked to DNA adducts associated with tobacco smoke exposure are predominantly found in the larynx. Presence of this class of mutation, termed COSMIC signature 4, is responsible for the increased burden of mutation in this anatomical sub-site. In addition, we show that another mutation pattern, COSMIC signature 5, is positively associated with age in HNSCC from non-smokers and that larynx SCC from non-smokers have a greater number of signature 5 mutations compared with other HNSCC sub-sites. Immunohistochemistry demonstrates a significantly lower Ki-67 proliferation index in size matched larynx SCC compared with oral cavity SCC and oropharynx SCC. Collectively, these observations support a model where larynx SCC are characterized by slower growth and increased susceptibility to mutations from tobacco carcinogen DNA adducts

The Role of Dental Hygienist in HPV Prevention and Education in Parents of Adolescents

Objectives/Aims: Today the Human Papillomavirus (HPV) infects nearly 14 million people each year in the United States alone. HPV is responsible for several cancers, including oropharyngeal, which is currently on the rise. Each year an estimated 53,000 cases of oropharyngeal cancers are diagnosed, with 70% of the cases related to HPV. The significance of educating dental providers and patients of the correlations between HPV and oropharyngeal cancers involves increased prevention strategies in dental practices. The aim is to begin offering multi-level education to adolescents’ parent’s in routine dental care visits, in order to provide an innovative approach to reduce HPV-related cancers. Methods: A sequence of MeSH terms were used to search the literature which included “HPV prevention strategies”, “Dental hygienist” and “HPV-related oropharyngeal cancer.” Results were refined to studies published within the last five years, excluding other countries outside the United States, and was centered to primary research sources. Results: The Human papillomavirus (HPV) has been shown to increase the rates of several cancers outside the cervical region, including cancers of the oropharynx. Evidence based research has discovered HPV vaccines that protect against strains of cervical cancer are likely to have the same effect in preventing HPV infections in the oropharynx. Researching the current data from The American Dental Education Association and PubMed Database, studies suggest that dental providers often feel uncomfortable providing HPV prevention with patients due to barriers: age, sexual orientation, and patient reactions. Dental providers should strongly consider implementing HPV prevention behaviors in dental practices to include HPV education, recommending the vaccine and referring patients for the vaccination. Conclusion: Compiling appropriate training along with refining dental providers self-efficacy to communicate HPV prevention strategies through continuing education. Along with expertise guided training in dental hygiene curricula could facilitate the process of reducing HPV-related cancers in the oral cavity.https://scholarscompass.vcu.edu/denh_student/1021/thumbnail.jp