DEVELOPMENT AND VALIDATION OF A PRE-SCREENING RISK- STRATIFICATION TOOL FOR ENHANCING THE PERFORMANCE OF ORAL CANCER SCREENING STRATEGIES

Aim:

The primary aim of our study is to develop and validate a pre-screening model capable of stratifying risk of oral cancer based on tobacco and alcohol consumption habits, enabling the proactive identification of individuals at an elevated risk of developing oral cancer.

Objectives:·       To assess the risk factors and estimate their strength of association with oral cancer through synthesis of existing evidence from literature (Phase 1).

·       To refine the existing risk stratification tool (OraCLE) with the results obtained from the systematic review and meta-analysis (Phase 1).

·       To validate OraCLE (Oral Cancer Likelihood Evaluator) in a hospital setting through a case- control study design (Phase 2).

·       To evaluate the ease of applicability and feasibility of implementing the model in a community setting (Phase 3).

Justification for study:

·       Evidence from several studies indicate that most oral cancers are detected in the later stages leading to poor prognosis and low treatment outcomes. The only way to overcome this is by implementing continuous screening processes at high-risk regions.

·       The major factor hindering the performance of oral cancer screening program is the process of selection of right target population. Although studies focus on all those who abuse tobacco/ alcohol, they fail to incorporate demographic profile and the degree of exposure to these carcinogens for an individual.

·       This emphasizes the need for a risk stratification tool like OraCLE that can categorize risk profiles of individuals exposed to carcinogens and also work as a pre-screening tool enabling selection of high-risk individuals for subsequent screening program.

·       OraCLE will not only be simple to implement but will also be resource-efficient considering the concerns of cost and accessibility of current screening programs.

·       Applying OraCLE as a pre-screening model at various regional and national level health centres, especially in the LMIC region can enable timely detection of the disease and also aid in bridging

the gap between disease identification and treatment, thereby curbing the oral cancer burden in the society.

Detailed description of procedure / processes:

Phase 1: Systematic review and meta-analysis:

·       To develop a comprehensive systematic review protocol and register the protocol in PROSPERO prior to initiation of search strategy.

·       To assess the risk factors and estimate their strength of association with oral cancer through synthesis of existing evidence from literature.

·       The risk factors with the highest strength of association shall be considered for incorporation in OraCLE.

·       To arrive at a refined version of OraCLE in this phase.

Phase 2:

·       Study participants shall be recruited and categorized as cases or controls based on the inclusion and exclusion criteria after obtaining the signed informed consent at their own will.

·       For each case, three controls shall be selected and will be age group (±5 years) and gender matched.

·       A pre-designed proforma shall be used to collect data about the subject’s demographics, socio- economic status, cancer history and exposure pattern to tobacco/alcohol. The history of oral cancer (applicable only to cases) will be extracted from medical records while rest of the data shall be collected through a brief interaction with the patient. The interaction will be quick and will take place during the patient’s waiting time in the OPD.

·       Interaction with the study subjects will be a one-time event as the study doesn’t require any follow-ups.

·       OraCLE shall be used to stratify the subjects as low, moderate, or high risk. Phase 3:

·       Study participants shall be recruited from the community through a house-to-house survey to check the tool’s feasibility. Health workers in the health centers shall also be included in the study.

·       Informed consent shall be obtained from all the study participants.

·       The recruited subjects shall be interviewed to collect their socio-demographic details and exposure patterns to tobacco/alcohol. The collected data shall be recorded in a pre-designed proforma.

·       A simple questionnaire shall be administered to assess the individual’s and health worker’s perception and acceptability of OraCLE.

·       The moderate and high-risk individuals recognized through the house-to-house survey will be provided with educational material (pictorial and written material in local language) about the ill-effects of tobacco and alcohol and about the behaviour modification strategies against use of tobacco/ alcohol. This will enable sensitizing the study population regarding harmful effects of tobacco and development of oral cancer. The individuals will also be directed towards a community health centre for further screening and intervention.

Sample size: Phase 1: All the eligible articles exploring the risk factors of oral cancer will be included for systematic review and meta-analysis.

Phase 2: Sample size is based on prediction ability of binary classifier model. The prediction ability is measured using area under ROC Curve (0-1 with 1 being good prediction ability).

Assuming area under ROC curve to be 0.85, based on literature (Amarasinghe et al., 2010) with 5% precision, the sample size needed in each group (cases and controls) is 130.

To increase the power of the study, the ratio of cases: control shall be taken as 1:3. Total sample size: 130 cases and 390 controls = 520 subjects.

 Phase 3:     Sample size (n) is estimated based on the formula below:

n = (z)2 p (1 – p) / d2 where,

z = 95% level of confidence (1.96)

p = Estimated proportion of the population that presents the characteristic (0.5) d = Tolerated margin of error (5%)

Using the formula above, we arrived at a sample size of 385.

Total sample size = 385 * 2 (Adjusting for design effect of 2) = 770. Number of health centers = 4

Sample size for each health center = 770/4 = 193.

193 general population from each health center attached to the Department of Community medicine, KMC, Manipal shall be recruited. The feasibility of OraCLE shall be evaluated in this phase by implementing the tool in the community, among the general population. Additionally, the health workers from the health centers will be eligible to participate in the study to check for the tool’s acceptability.

  Outcome measures:The outcome measures in this study will be:

·       Risk factors and their strength of association with oral cancer (Phase 1).

·       Sensitivity, specificity, and predictability of OraCLE in risk stratification of oral cancer (Phase 2).

·       The degree of exposure to tobacco/alcohol among cases and control (Phase 2).

·       Feasibility and ease of applicability of OraCLE (Phase 3).

·       To arrive at a scientifically validated, feasible, user-friendly, and generalizable pre-screening tool for oral cancer.