Evaluation of screening for nasopharyngeal carcinoma: trial design using Markov chain models

In this paper, we develop a Markov chain model to estimate parameters pertaining to the natural history of nasopharyngeal carcinoma (NPC). The model is of progression from no disease to Epstein-Barr virus (EBV) infection, preclinical screen-detectable tumour and clinical tumour. We derive tentative estimates of the parameters of the model, based on limited published data, to assess the efficacy of serum screening in conjunction with clinical assessment (indirect mirror examination for NPC), for example the average duration of the preclinical screen-detectable phase is estimated as 3.1 years. We further apply these parameters to a hypothetical screening trial in the Hong Kong population to assess the efficacy of serum screening with clinical assessment by different combinations of screening regime. Results suggest: (1) there is no substantial difference between 3-yearly and 6-yearly serum screening; and (2) within the same serum screening regime annual and 3-yearly clinical assessment can prevent 33% and 28% of deaths from NPC respectively. Prediction of deaths and surrogate end points can be used to estimate the required sample size and duration for designing a randomized trial of screening for NPC. Based on these findings and power projections, we suggest a design for a randomized trial in a high incidence area such as Hong Kong.