Sreenath Madathil

No role for human papillomavirus infection in oral cancers in a region in southern India

Oral cancer is a major public health issue in India with ∼77,000 new cases and 52,000 deaths yearly. Paan chewing, tobacco and alcohol use are strong risk factors for this cancer in India. Human papillomaviruses (HPVs) are also related to a subset of head and neck cancers (HNCs). We examined the association between oral HPV and oral cancer in a sample of Indian subjects participating in a hospital‐based case‐control study. We recruited incident oral cancer cases (N = 350) and controls frequency‐matched by age and sex (N = 371) from two main referral hospitals in Kerala, South India. Sociodemographic and behavioral data were collected by interviews. Epithelial cells were sampled using Oral CDx® brushes from the oral cancer site and the normal mucosa. Detection and genotyping of 36 HPV genotypes were done using a polymerase chain reaction protocol. Data collection procedures were performed by qualified dentists via a detailed protocol with strict quality control, including independent HPV testing in India and Canada. HPV DNA was detected in none of the cases or controls. Associations between oral cancer and risk factors usually associated with HPV infection, such as oral sex and number of lifetime sexual partners, were examined by logistic regression and were not associated with oral cancer. Lack of a role for HPV infection in this study may reflect cultural or religious characteristics specific to this region in India that are not conducive to oral HPV transmission. A nationwide representative prevalence study is needed to investigate HPV prevalence variability among Indian regions.

Antihypertensive Medications and the Survival Rate of Osseointegrated Dental Implants: A Cohort Study

PURPOSE Antihypertensive drugs in general are beneficial for bone formation and remodeling, and are associated with lower risk of bone fractures. As osseointegration is influenced by bone metabolism, this study aimed to investigate the association between antihypertensive drugs and the survival rate of osseointegrated implants. MATERIALS AND METHODS This retrospective cohort study included a total of 1,499 dental implants in 728 patients (327 implants in 142 antihypertensive-drugs-users and 1,172 in 586 nonusers). Multilevel mixed effects parametric survival analyses were used to test the association between antihypertensive drugs use and implant failure adjusting for potential confounders. RESULTS Only 0.6% of the implants failed in patients using antihypertensive drugs while 4.1% failed in nonusers. A higher survival rate of dental implants was observed among users of antihypertensive drugs [HR (95% CI): 0.12 (0.03-0.49)] compared to nonusers. CONCLUSIONS Our findings suggest that treatment with antihypertensive drugs may be associated with an increased survival rate of osseointegrated implants. To our knowledge, this could be the first study showing that the systemic use of a medication could be associated with higher survival rate of dental implants.

Periodontal diseases and risk of oral cancer in Southern India: Results from the HeNCe Life study

Some studies suggest that periodontal diseases increase the risk of oral cancer, but contradictory results also exist. Inadequate control of confounders, including life course exposures, may have influenced prior findings. We estimate the extent to which high levels of periodontal diseases, measured by gingival inflammation and recession, are associated with oral cancer risk using a comprehensive subset of potential confounders and applying a stringent adjustment approach. In a hospital‐based case‐control study, incident oral cancer cases (N = 350) were recruited from two major referral hospitals in Kerala, South India, from 2008 to 2012. Controls (N = 371), frequency‐matched by age and sex, were recruited from clinics at the same hospitals. Structured interviews collected information on several domains of exposure via a detailed life course questionnaire. Periodontal diseases, as measured by gingival inflammation and gingival recession, were evaluated visually by qualified dentists following a detailed protocol. The relationship between periodontal diseases and oral cancer risk was assessed by unconditional logistic regression using a stringent empirical selection of potential confounders corresponding to a 1% change‐in‐estimates. Generalized gingival recession was significantly associated with oral cancer risk (Odds Ratio = 1.83, 95% Confidence Interval: 1.10–3.04). No significant association was observed between gingival inflammation and oral cancer. Our findings support the hypothesis that high levels of periodontal diseases increase the risk of oral cancer.

Human papillomavirus genotypes and risk of head and neck cancers: Results from the HeNCe Life case-control study

OBJECTIVE Human papillomaviruses (HPV) are changing dramatically the epidemiologic landscape of head and neck cancers (HNCs). Their role in the aetiology of these cancers varies widely among HNCs subsites, sex and geographical regions worldwide. We describe HPV prevalence and its association with HNCs risk overall and by anatomical subsite in a sample of Canadians. MATERIALS AND METHODS The HeNCe Life study recruited 460 incident HNCs cases and 458 controls frequency-matched by age and sex from four Montreal hospitals in 2005-2013. We tested oral rinse and oral brush specimens for mucosal HPV genotypes. HPV positivity was categorized hierarchically as either negative, exclusively non-α-9 species types, α-9 types other than HPV16, and HPV16. We estimated odds ratios (OR) and 95% confidence intervals (CI) for the associations between HPV and HNCs using unconditional logistic regression, controlling for confounders. RESULTS The prevalence of HPV infection among controls and cases was 14.5% and 41.2% in oral rinse and 3.1% and 24.4% in oral brush samples, respectively. HPV16 was the predominant genotype with an oral rinse and oral brush prevalence of 26.3% and 16.2% among cases and 2.4% and 0.2% among controls, respectively. HPV infection was associated with an increased risk of HNCs overall (OR=4.18; 95% CI, 2.94-5.95) and oropharyngeal cancer only (OR=10.3; 95% CI, 6.8-15.7). HNCs and oropharyngeal cancer were strongly associated with HPV16 (OR=18.1; 95% CI, 9.1-35.8, and OR=47.2; 95% CI, 23.1-96.6, respectively). CONCLUSION HPV infection, particularly HPV16, was associated with an increased HNCs risk, most strongly for oropharyngeal cancers.

Nonlinear association between betel quid chewing and oral cancer: Implications for prevention

PURPOSE Betel quid chewing is a major oral cancer risk factor and the human papillomaviruses (HPV) may play an aetiological role in these cancers. However, little is known about the shape of the dose-response relationship between the betel quid chewing habit and oral cancer risk in populations without HPV. We estimate the shape of this dose-response relationship, and discuss implications for prevention. METHODS Cases with oral squamous cell carcinoma (350) and non-cancer controls (371) were recruited from two major teaching hospitals in South India. Information on socio-demographic and behavioral factors was collected using a questionnaire and the life grid technique. The effect of daily amount of use and duration of the habit were estimated jointly as risk associated with cumulative exposure (chew-years). The shape of the dose-response curve was estimated using restricted cubic spline transformation of chew-years in a conditional logistic regression model. Risk estimates for low dose combinations of daily amount and duration of the habit were computed from flexible regression. RESULTS Most (72%) oral cancer cases were betel quid chewers in contrast to only 18% of controls. A nonlinear dose-response relationship was observed; the risk increased steeply at low doses and plateaued at high exposures to betel quid (>425 chew-years). A threefold increase in risk (OR=3.92, 95%CI: 1.87-8.21) was observed for the lowest dose; equivalent to the use of one quid per day for one year. CONCLUSION Our findings may be used to counsel people to refrain from even low betel quid chewing.

Aetiological heterogeneity of head and neck squamous cell carcinomas: the role of human papillomavirus infections, smoking and alcohol

Tobacco and alcohol consumption are the main risk factors for head and neck squamous cell carcinoma (HNSCC). In addition, human papillomavirus (HPV) infection plays a causal role in oropharyngeal cancer (OPC), a subset of HNSCC. We assessed the independent effects of tobacco, alcohol and HPV infection on OPC risk in the head and neck cancer (HeNCe) Life study, a hospital-based case-control study of HNSCC with frequency-matched controls by age and sex from four Montreal hospitals. Interviewers collected information on socio-demographic and behavioural factors. We tested exfoliated oral cells for HPV DNA by polymerase chain reaction (PCR). We included only OPC cases (n = 188) and controls (n = 427) without missing values for HPV, smoking or alcohol. We examined associations by estimating odds ratios (ORs) and corresponding 95% confidence intervals (CI) using unconditional logistic regression. Smoking (OR = 1.90, 95% CI: 1.04-3.45) and alcohol (OR = 2.74, 95% CI: 1.45-5.15) were associated with an increased risk of OPC independent of HPV status. Positivity for HPV 16 among heavy smokers and heavy alcohol users was associated with a 30.4-fold (95% CI: 8.94-103.26) and 18.6-fold (95% CI: 5.75-60.13) elevation in risk of OPC relative to participants who were HPV negative, respectively. Moreover, the combined effect of heavy smoking and alcohol comsumption with HPV 16 infection substantially increased OPC risk (OR = 48.76, 95% CI: 15.83-150.17) and (OR = 50.60, 95% CI: 15.96-160.40), respectively. Our results support the independent roles of smoking, alcohol and HPV infection in OPC risk and a possible combined effect. Efforts should be made to tackle these major risk factors simultaneously.

Tuibur: tobacco in a bottle-commercial production of tobacco smoke-saturated aqueous concentrate: Tuibur- tobacco in a bottle

Certain forms of tobacco that are relatively unknown in the scientific community have been used widely for centuries. One such form is tuibur [1,2], a tobacco smoke-saturated aqueous concentrate prevalent in north-eastern India [3]. The highest prevalence of tobacco consumption in India occurs in the northeastern province of Mizoram [4,5], where the Aizawl District also leads the incidence rates of all tobacco-related cancers in the country [6]. Yet references to tuibur use are rare and restricted mainly to local publications [3,7–12]. This commentary aims to raise awareness and stimulate research on this tobacco product about which little is known. We describe its production and distribution with the support of photographs to contextualize this knowledge for readers. Historically, women smoked tobacco in waterpipes made of bamboo (Fig. 1), and would offer the leftover tobacco-infused water from the pipe reservoir to their husband [10]. Users keep a small amount (5–10 ml) of liquid in the mouth for many minutes several times throughout the day; some may also swallow a portion of the liquid [13]. Increased demand for the product moved production from households to makeshift sheds located near natural water sources (Fig. 2). Indeed, concern over its environmental and health impact may help to explain why tuibur is produced in small batches in artisanal facilities [14–16]. The production of a fresh batch of tuibur starts early in the morning. First, water is alkalized by being filtered through tobacco ash from the previous batch (Supporting information, Fig. S1). Alkaline pH maintains an unprotonated form of nicotine that is absorbed easily through the oral mucosa [1]. This solution is then poured into the lower chamber of a device (Fig. 3) with a rudimentary water educator (aspirator). A pipe is inserted into this chamber with one end just below the water level, and sealed with mud (Fig. 3). The upper half of the device, the combustion chamber, is connected to the lower chamber through a filtered opening at the bottom. Dried tobacco stalk is placed in the combustion chamber and set to smoulder (Supporting information, Fig. S2). Subsequently, this chamber is sealed with wet tobacco ash. The pressure from a stream of water creates a suction in the smaller pipes, which ensures that tobacco smoke bubbles through the alkaline solution. The process

Periodontal Diseases and Traumatic Dental Injuries in the Pediatric Population

This article provides an overview of periodontal diseases and traumatic dental injuries (TDIs) in children and adolescents, which are serious public health problems worldwide. Periodontal diseases, including gingivitis and periodontitis, commonly affect the oral soft tissues and teeth and often co-occur with other chronic diseases. TDIs are prevalent from an early age and carry high treatment costs. Behavioral and environmental factors contribute to both TDIs and periodontal diseases, but their etiology varies according to population characteristics and case definition. Both conditions may lead to pain, function impairment, esthetic problems, and psychosocial effects, with major consequences on quality of life.

Efficacy of metformin in the management of periodontitis: A systematic review and meta-analysis

Periodontitis is characterized by inflammation of the periodontium and leads to loss of teeth if untreated. Although a number of surgical and pharmacological options are available for the management of periodontitis, it still affects a large proportion of population. Recently, metformin (MF), an oral hypoglycemic, has been used to treat periodontitis. The aim of this review is to systematically evaluate the efficacy of MF in the treatment of periodontitis. An electronic search was carried out using the keywords ‘metformin’, ‘periodontal’ and ‘periodontitis’ via the PubMed/Medline, ISI Web of Science and Google Scholar databases for relevant articles published from 1949 to 2016. The addressed focused question was: ‘Is metformin effective in reducing bone loss in periodontitis? Critical review and meta-analysis were conducted of the results obtained in the selected studies. Following the removal of the duplicate results, the primary search resulted in 17 articles and seven articles were excluded based on title and abstract. Hence, 10 articles were read completely for eligibility. After exclusion of four irrelevant studies, six articles were included. The topical application of MF resulted in improved histological, clinical and radiographic outcomes. Additionally, results from the meta-analysis indicated that application of metformin improved the clinical and radiographic outcomes of scaling and root-planing, but at the same time heterogeneity was evident among the results. However, because of a lack of histological and bacterial studies, in addition to short follow-up periods and risk of bias, the long-term efficacy of MF in the treatment of bony defects is not yet ascertained. Further studies are needed to envisage the long-term efficacy of MF in the management of periodontitis.

Inconclusive evidence Exists regarding the association between dental caries and BMI in children under age 18 years

Selection Criteria Three electronic databases (PubMed, Embase, and Cochrane Library) were searched for observational studies pertinent to the association between BMI and dental caries. The selection criteria included (1) study population: children under age 18 years; (2) a clear definition of BMI with 4 or more categories; and (3) availability of a caries index specific to both primary and permanent dentitions. Studies with no direct comparison, reviews, abstracts, and letters were excluded. Key Study Factor BMI information was to be clearly defined and divided into underweight, normal weight, overweight, and obese categories. Dental caries index when assessed in a mixed dentition population was reported separately for primary and permanent dentition. Studies on special populations and previous systematic reviews were excluded. No restriction on the study design of primary research was used. Main Outcome Measure The main outcome measure was mean caries experience index, which was defined as the decayed‐missing‐filled tooth (DMFT)/decayed‐missing‐filled surface for the permanent dentition and dmft/deft for the primary dentition. Main Results Fourteen cross‐sectional studies were included in the final analysis from the initial 148 potentially relevant studies. The included studies were only of low to medium quality based on a modified version of the Agency for Healthcare Research and Quality checklist. Moreover, the findings from studies included considerable heterogeneity even in subgroup analysis. The authors attributed some of this heterogeneity to publication bias. Four patterns of association were found among the included studies: inconclusive, positive, inverse, and U‐shaped. Subsequently, the pooled estimates were mostly inconclusive with wide confidence intervals (CIs), except for the overweight‐to‐normal weight and obesity‐to‐normal weight comparisons in high‐income countries (weighted mean = 0.28; 95% CI = 0.01‐0.54, weighted mean = 0.52; 95% CI = 0.01‐1.03). Conclusion There is a prominent level of heterogeneity among the findings of the included cross‐sectional, unadjusted associations between BMI and dental caries. Further well‐designed prospective studies are required to confidently infer any association.