==== Front Cureus Cureus 2168-8184 Cureus 2168-8184 Cureus Palo Alto (CA) 10.7759/cureus.39786 Oncology Dentistry Health Policy A Systematic Review and Meta-Analysis Assessing the Role of Oral Health as a Risk Factor in Oral Cancer Muacevic Alexander Adler John R Mahuli Amit V 1 Sagar Vidya 2 Kumar Amit 3 Mahuli Simpy A 4 Kujur Anit 2 1 Public Health Dentistry and Preventive Dentistry, Dental College, Rajendra Institute of Medical Sciences, Ranchi, IND 2 Preventive and Social Medicine, Rajendra Institute of Medical Sciences, Ranchi, IND 3 Laboratory Medicine, Rajendra institute of Medical Sciences, Ranchi, IND 4 Dentistry, Rajendra Institute of Medical Sciences, Ranchi, IND Amit V. Mahuli amitmahuli@gmail.com 31 5 2023 5 2023 15 5 e3978631 5 2023 Copyright © 2023, Mahuli et al. 2023 Mahuli et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This article is available from https://www.cureus.com/articles/160778-a-systematic-review-and-meta-analysis-assessing-the-role-of-oral-health-as-a-risk-factor-in-oral-cancer Oral squamous cell carcinoma is the leading type of cancer in Southeast Asian countries and many parts of the world. Many factors increase the risk of oral cancer, like tobacco, betel nuts, alcohol consumption, sharp teeth, infections, and other factors. Oral health-related issues have been reported in many studies of oral cancer, but there is a need to understand the role of the same as a risk factor. The systematic review and meta-analysis were conducted to assess the role of oral health as a risk factor in oral cancer. The population diagnosed with oral cancer (P) of all age groups and both gender, exposure (E) is oral health (includes poor oral hygiene, periodontal disease, and other oral diseases excluding oral potentially malignant disorders (OPMD)), the comparator (C), is patients without oral health issues, outcome (O) is the role of poor oral health as a risk factor for oral cancer. A systematic review and meta-analysis were conducted. The databases used for the search were PubMed, Cochrane Database, Embase, Scopus, and Google Scholar. The unpublished reports, reviews, and grey literature were considered. Case-control studies were included assessing poor oral health as a risk factor with odds ratio as an effective measure. Newcastle Ottawa Scale for risk of bias in the case-control study was considered. The study results showed that tooth loss odds ratio (OR)=1.13, CI (0.99-1.26), I2 value of 71.7%, Oral hygiene OR=1.29, CI (1.04-1.54), I2 value of 19.7% and in periodontal diseases OR=2.14 CI (1.70-2.58), I2 value of 75.3% had a higher risk of developing oral cancer. The risk factors for tooth loss and periodontal disease showed moderate heterogenicity and less heterogenicity for oral hygiene. Poor oral health factors such as periodontal disease, poor oral hygiene, and loss of teeth show higher odds of oral cancer than the control. The periodontal disease shows the highest odds than other factors. These risk factors can be considered for the primordial prevention of oral cancer. meta-analysis risk factor tooth loss periodontal disease poor oral health oral cancer ==== Body pmcIntroduction and background With more than 350,000 new cases of oral cancer detected each year, it is a significant public health issue. The incidence of oral cancer varies significantly by geographic location, with Southeast Asia, South Asia, and portions of Europe reporting the highest rates. More than 60% of all occurrences of oral cancer are recorded from Southeast Asian nations, making it the most common type of cancer there, with India accounting for a 9.8 Age-standardized incidence rate in the year 2020 in both genders and all ages of lip and oral cavity cancer. Regarding demographics, men are more likely than women to develop oral cancer, and the risk rises with age [1]. Squamous cell carcinomas, which comprise the bulk of oral malignancies, are linked to the consumption of alcohol, smoking cigarettes, chewing of tobacco, and having the human papillomavirus (HPV) infection [2]. A family history of cancer, poor dental hygiene, persistent mouth inflammation, and occupational exposure to asbestos, nickel, and wood dust are additional risk factors for oral cancer. Oral cancer must be detected early to be successfully treated; hence routine dental exams should include oral cancer screenings. The stage of diagnosis affects the five-year survival rate for oral cancer, with early-stage tumors having a substantially greater survival rate than advanced-stage cancers [3,4]. Alcohol intake reduction, HPV vaccination, and tobacco cessation programs are all effective oral cancer prevention measures. Campaigns for public health education can also significantly impact spreading knowledge about the value of early detection and promoting healthy habits to lower the incidence of oral cancer [5]. Studies on serval populations have revealed a link between oral cancer, periodontal disease, and tooth loss. Because of their increased cellularity, chronic infections produce free radicals that can damage DNA and trigger mutations that culminate in carcinogenesis. Studies have linked oral hygiene (such as brushing) to oral cancer. Only a few research have examined the relationship between the frequency of dental visits and the risk of oral cancer [6-8]. The oral health-related risk factors must be thoroughly investigated, like poor oral health, periodontitis (bleeding gums, mobile teeth), loss of teeth (edentulous state), and other indicators. They can help create awareness and support the primordial prevention of oral cancer. Thus, the systematic review and meta-analysis aimed to assess the role of oral health as a risk factor in oral cancer. Review Methodology The systematic review and meta-analysis were registered in PROSPERO with the registration number CRD42022311263 dated March 25, 2022 before the start of the study. PICO Question The population diagnosed with oral cancer (P) of all age groups and both gender, exposure (I/E) is oral health (includes poor oral hygiene, periodontal disease, and other oral diseases excluding Oral potentially malignant disorders (OPMD)), The comparator (C), is patients without oral health issues, outcome (O), is the role of poor oral health as a risk factor for oral cancer. Eligibility Criteria and Inclusion Case-control studies were included in assessing poor oral health as a risk factor. The effect Measure was considered to be an Odds ratio with a Confidence Interval of 95%. Population aged 18 years and above in both genders. Information Source The databases used for the search were PubMed, Cochrane Database, Embase, Scopus, and Google Scholar. The unpublished reports, reviews, and grey literature were considered. Search Strategy Poor oral health and oral cancer Filters: Abstract, Free full text, Full text, Humans(("poverty"[MeSH Terms] OR "poverty"[All Fields] OR "poor"[All Fields]) AND ("oral health"[MeSH Terms] OR ("oral"[All Fields] AND "health"[All Fields]) OR "oral health"[All Fields]) AND ("mouth neoplasms"[MeSH Terms] OR ("mouth"[All Fields] AND "neoplasms"[All Fields]) OR "mouth neoplasms"[All Fields] OR ("oral"[All Fields] AND "cancer"[All Fields]) OR "oral cancer"[All Fields])) AND ((ffrft[Filter]) AND (fha[Filter]) AND (fft[Filter]) AND (humans[Filter])) with keywords poor oral health, poor oral hygiene, periodontal disease, and oral cancer. Selection Process Two reviewers assessed the studies for inclusion. The titles and abstracts of publications were read and categorized first. The texts of the possibly relevant publications were then evaluated, with a final selection of studies being considered for inclusion in the review. The reviewers were educated, and their work was monitored. Responses have been calibrated, and an inter-examiner agreement of more than 80% was expected. A third examiner looked for more relevant material found in the reference lists of the papers and review articles that were included. The fourth and final reviewer was contacted in the event of any discrepancies; he acted as an expert and guide. Data Extraction Data were extracted by the authors. Questions about the abstracted data were resolved through discussion by two reviewers working independently among the reviewers. Data from approved research were extracted into a data extraction sheet and then analyzed. Data Items Information about the study (author, date, publishing site, total sample size, study type, event rates, odds ratio, confidence interval and the index used to find it). Descriptors of participants (age range, gender, population size, and relevant context). Oral health issues as a risk factor in oral cancer. The periodontal status (bleeding gums, attachment loss), oral hygiene, and tooth loss. Risk of bias was reported using New Castle Ottawa Scale (Table 1) [9]. Table 1 Newcastle-Ottawa Quality Assessment Scale case-control studies. Category                                                                          Item check                                                                                                                                                      Score Selection (Maximum four stars) 1. Is the case definition adequate? 1 2. Representativeness of the cases 1 3. Selection of controls 1 4. Definition of controls 1 Comparability (Maximum two stars) 5. Comparability of cases and controls based on the design or analysis 1 1 Outcome (Maximum three stars) 6. Ascertainment of exposure 1 7. Same method of ascertainment for cases and controls 1 8. Non-response rate 1   Total Score 9 Effect Measure Odds ratio with a Confidence Interval of 95% was considered. Synthesis Methods The descriptive data were collected from the selected studies, and a meta-analysis was carried out to assess the role of poor oral health as a risk factor for oral cancer. The oral health indicators studies were divided into periodontal disease (19 studies), oral hygiene (17 studies) and loss of teeth (24 studies) from a total of 27 full-text studies qualifying to be included in the meta-analysis. Statistical Plan The data were analyzed using Stata Version 14; random effects model was used to develop the funnel plot using the Odds ratio, and the confidence interval and degree of heterogeneity were analyzed accordingly. The (I)square value was calculated. Meta-regression analysis was done, and a funnel plot was plotted to check for publication bias. The risk of bias analysis for each study was done using the New Castle Ottawa quality assessment scale for case-control studies, which has three main domains: selection, comparability, Outcome, and a total of nine-point item score. Results Study Selection and Characteristics A total of 1,965 records were included after the search from various databases after the removal of duplicates. Then the articles were screened for appropriateness with the inclusion criteria, mainly studies with keywords like oral cancer and oral health that includes poor oral health, periodontitis (bleeding gums, mobile teeth), loss of teeth (edentulous state) were screened, and 1877 records were excluded. The remaining 88 records were checked for study design (case-control studies), full-text articles, effect measure (odds ratio) and appropriateness of key search terminologies. A total of 27 articles (Table 1) were selected and then divided as articles on periodontal disease (19 articles), articles on oral hygiene (17 studies) and articles on loss of teeth (24 articles) were selected for sub-group analysis (Figure 1). Figure 1 Flow chart showing the selection of the studies for meta-analysis The risk of bias scores of all articles is mentioned in Table 2 out of a total score of nine [10-36]. Table 2 Descriptive characteristics of all the studies involved in the meta-analysis.* *27 articles were extracted, male and female data represented separately for articles and two centers data in one article, total resulting in 30 set of data. M=Male, F=Female, NA=Not applicable S.No Author Year  Study Origin  Mean Age case sample size  control sample size  Gender  Quality Score  Odds ratio for Tooth loss Odds ratio for Periodontal disease  odds ratio for oral hygiene 1 Balaram [10] 2002 India 22-85 307 291 Male 9 3.89 2.83 0.96 2 Balaram [10] 2002 India 18-87 278 290 Female 9 7.61 3.35 3.39 3 Bundgaard et al. [11] 1995 Denmark < 45- >75 161 483 M&F 9 2.4 NA NA 4 Chang [12] 2013 China 20-80 317 296 M&F 9 2.4 3.11 1.45 5 Divaris [13] 2010 USA 20-80 692 1361 M&F 8 1.05 NA NA 6 Eliot [14] 2013 USA 18 years and older 148 567 M&F 9 NA 1.07 NA 7 Farquhar et al. [15] 2017 USA 59.4 679 333 M&F 8 0.88 1.24 0.93 8 Guha [16] 2007 Latin american 0-75+ 309 1208 M&F 8 0.48 1.94 1.37 9 Guha [16] 2007 Europe 0-75+ 146 566 M&F 8 1.2 NA 1.2 10 Gupta [17] 2017 India 57.3 187 240 M&F 7 2.04 3.94 2.16 11 Huang [18] 2015 China cases 58.02 control57.15 414 870 M&F 9 3.51 NA NA 12 Kawakita et al. [19] 2017 China 18-85 921 806 M&F 8 1.49 NA 1.13 13 Laprise [20] 2016 India 59.4 306 328 M&F 7 NA 2.28 NA 14 Garrote [21] 2001 CUBA 25-88 200 200 M&F 9 2.74 2.3 1.94 15 Lissowska [22] 2003 Poland 23-80 122 124 M&F 7 9.85 4.33 3.24 16 Marques [23] 2008 Brazil 40-70 168 406 M&F 7 0.7 3 1.5 17 Marshall [24] 1992 USA 18-76 290 290 M&F 7 2.7 NA NA 18 Mazul et al. [25] 2016 USA 20-80 1396 276 M&F 9 0.85 0.97 NA 19 Moergel [26] 2013 Germany 37-88 178 123 M&F 8 NA 2.4 NA 20 Rosenquist [27] 2005 Sweden 33-87 132 320 M&F 7 3.4 NA 5.3 21 Saira [28] 2019 Pakistan 55 cases, 52.8 controls 276 275 M&F 5 2.56 4.05 2.01 22 Shewale et al. [29] 2021 USA 18-80 114 228 M&F 7 4.55 1.44 2.25 23 Shin [30] 2019 South Korea 63.8 cases, 64.4 controls 146 278 M&F 7 9.99 3.66 NA 24 Talamini [31] 2000 Italy 27-86 132 148 M&F 8 1.4 3.9 1.4 25 Tezal [32] 2009 USA 56.9 100 207 M&F 9 1.02 4.3 NA 26 Tezal [33] 2007 USA 25-87 51 54 M&F 7 0.95 5.23 NA 27 Tezal [34] 2013 USA 58.62 cases, 54.35 controls 399 221 M&F 5 1.57 NA NA 28 Zheng et al. [35] 1990 China 18-80 248 156 Male 8 3.7 NA 6.9 29 Zheng et al. [35] 1990 China 18-80 248 156 Female 8 8.3 NA 2.5 30 Zuo [36] 2015 China 59 150 167 M&F 6 3.64 NA NA Meta-Analysis Findings for Tooth Loss The pooled analysis observed that 1.13 times non-significantly higher risk for tooth loss compared to control (OR, 1.13; 95% CI 0.99 to 1.26) with significantly higher heterogeneity (I2=71.7%) (Figure 2, Table 3). The meta-regression analysis did not observe the statistically significant heterogeneity due to methodological quality score in the pooled effect size for tooth loss (Figure 3). Funnel plot shows symmetry indicating the absence of publication bias (Figure 4). Figure 2 Forest plot showing the meta-analysis results for tooth loss as a risk factor (24 studies) [10-13,15-19,21-25,27-36] Table 3 Meta-analysis results for tooth loss as a risk factor. Results for tooth loss     Meta-regression Number of observations 25 REML estimate of between-study variance tau2 0.7411 % residual variation due to heterogeneity  I-squared_res 71.75% Proportion of between-study variance explained Adj R-squared  -15.76% Figure 3 Meta-regression for tooth loss as risk factors Figure 4 Funnel plot for tooth loss as risk factors for publication bias Meta-Analysis Findings on Oral Hygiene The pooled analysis observed that 1.29 times significantly higher risk for oral hygiene compared to the control (OR, 1.29; 95% CI 1.04 to 1.54) (Figure 5) with homogeneity in finding (I2=19.7%) (Table 4). The meta-regression analysis did not observe the statistically significant heterogeneity due to methodological quality score in the pooled effect size for oral hygiene (Figure 6). Funnel plot shows asymmetry indicating the presence of publication bias (Figure 7). Figure 5 Forest plot showing the meta-analysis results for oral hygiene as a risk factor (17 studies) [10,12,13,15-17,19,21-25,27-33,35,36] Table 4 Meta-analysis results for oral hygiene as a risk factor. Results for oral hygiene as a risk factor     Meta-regression Number of observations 16 REML estimate of between-study variance tau2 0.05399 % residual variation due to heterogeneity  I-squared_res 15.26% Figure 6 Meta-regression for oral hygiene as risk factors Figure 7 Funnel plot for oral hygiene as risk factors for publication bias Meta-Analysis Findings for Periodontal Disease The pooled analysis observed that 2.14 times significantly higher risk for periodontal disease compared to control (OR, 2.14; 95% CI 1.70 to 2.58) (Figure 8) with significant heterogeneity in finding (I2=75.3%) (Table 5). The meta-regression analysis did observe the decrease in effect size with an increase in quality for periodontal disease (Figure 9). Funnel plot shows asymmetry indicating the presence of publication bias (Figure 10). Figure 8 Forest plot showing the meta-analysis results for periodontal disease as a risk factor (19 studies) [10,12,14-17,20-23,25,26,28-33] Table 5 Meta-analysis results for periodontal disease as a risk factor. Results for periodontal disease as a risk factor     Meta-regression Number of observations 19 REML estimate of between-study variance tau2 0.9939 % residual variation due to heterogeneity  I-squared_res 68.63% Proportion of between-study variance explained Adj R-squared 1.28% Figure 9 Meta-regression for periodontal disease as risk factors Figure 10 Funnel plot for periodontal disease as risk factors for publication bias Discussion The meta-analysis considered the odds ratio as an effect measure. The data extraction was done in detail with the number of cases, controls, case events and control events. The studies included in the analysis didn't show a standardized variable reporting method. Many studies have reported oral health (tooth loss, periodontal disease, oral hygiene) as a risk factor for oral cancer. However, the parameters considered in each of these vary, leading to the heterogenicity of the meta-analysis. Thus, the random-effect model was chosen for the analysis [2,6,7,14]. A total of 24 studies on tooth loss were considered, with 27 entries, as male, female and region-wise data was entered as separate entities from the same studies. Studies reported tooth loss variables in different measurements (missing more than 16, missing more than 20, missing more than five, only five present) leading to moderate heterogenicity of 71.7% (I2 value) and an OR of 1.13 and CI of (0.99-1.26), showing higher odds of oral cancer with tooth loss than controls [24,27,31]. The oral hygiene practices showed less heterogenicity of 19.7% (I2 value) as brushing habit was recorded uniformly in almost all studies, brushing less than once daily, once daily and twice daily and showed a pooled OR of 1.29, indicating higher odds of oral cancer who less brush (poor oral hygiene) than controls [12,15].­ Likewise, in periodontal disease, measurements considered were gum bleeding, loss of attachment, and bone loss, thus leading to heterogenicity of 75.3% (I2 value) [14,20,26,30,32,33]. The presence of periodontal infection shows higher odds (OR 2.14, CI, 1.70-2.58) of oral cancer than the controls, which was statistically significant. The probable reason being reactive oxygen species, reactive nitrogen species, reactive lipids and metabolites, and matrix metalloproteases are also produced by microbes and microbial toxins in host cells and epithelial cells. These substances can potentially damage epithelial cells' DNA and trigger the creation of cytokines, chemokines, growth factors, and other substances that support disrupting the normal control of cell growth and can promote carcinogenesis [7,8]. The oral health risk factors tooth loss, periodontal disease and oral hygiene are the sequel of events that occur from poor oral hygiene (lack of brushing teeth) leading to periodontal disease (gingivitis, periodontitis) and thus to tooth loss. This emphasizes the role of prevention of oral disease and proper oral hygiene, including interdental hygiene, in limiting oral health risk factors in the occurrence of oral cancer [23,26,30]. Many studies have reported poor oral health as a risk factor in nasopharyngeal, pharyngeal and cancer of other head and neck regions. A previous meta-analysis conducted by Shuai in the year 2019 analyzed all methods to describe oral health together and reported a heterogenicity of 85%. Whereas, in the present meta-analysis, tooth loss, oral hygiene and periodontal disease were analyzed individually to get closer to evidence [37]. The meta-analysis highlights periodontal disease as an independent risk factor for oral cancer, followed by poor oral hygiene and tooth loss. However, owing to the moderate heterogenicity and publication bias, there is scope for more studies with a larger sample size. Also, more defined and standardized recording of the variables like, periodontal, oral hygiene and tooth loss need to be followed for more robust analytics. The meta-analysis considered few databases commonly accessible and full text availability of articles were few limitations to be noted. Nevertheless, there is clear evidence that poor oral health can be a risk factor for oral cancer. This indicates good oral hygiene and prevention of oral disease are vital in primordial prevention of oral cancer. Conclusions The periodontal disease shows higher odds of oral cancer when compared to the controls with moderate heterogenicity in the studies considered. The results indicate periodontal disease as a potential risk factor for oral cancer as chronic infection contributes to the occurrence of cancer, followed by oral hygiene with low heterogenicity and tooth loss with moderate heterogenicity; however, there is scope for more multicentric trials or individual studies with a standardized reporting of variables, with larger sample size, event rates and lesser risk of bias in generating more robust evidence. The results indicate that better oral healthcare, oral hygiene practices, and prevention of oral diseases can prevent one of the risk factors leading to oral cancer. The authors have declared that no competing interests exist. ==== Refs References 1 Globocan 2020 lip and oral cavity factsheet 1 2023 2020 https://gco.iarc.fr/today/data/factsheets/cancers/1-Lip-oral-cavity-fact-sheet.pdf 2 Head and neck squamous cell carcinoma Nat Rev Dis Primers Johnson DE Burtness B Leemans CR Lui VW Bauman JE Grandis JR 92 6 2020 33243986 3 Early detection of oral cancer: a key role for dentists? J Cancer Res Clin Oncol Hertrampf K Jürgensen M Wahl S Baumann E Wenz HJ Wiltfang J Waldmann A 1375 1387 148 2022 35249159 4 Early diagnosis of oral cancer Cancer Silverman Jr S 1796 1799 15 1988 5 Oral cancer prevention and control-the approach of the World Health Organization. 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