Analysis of risk factors for multiple primary oral squamous cell carcinoma: a cohort study

Chewing betel quid (CBQ) is popular in Southeast Asia, resulting in a high incidence of oral squamous cell carcinoma (OSCC). The incidence of multiple primary oral cancer (MPOC) has gradually increased and has become one of the main causes of OSCC treatment failure. However, it is unclear whether the high incidence of MPOC is also correlated with the habit of CBQ.

In this retrospective study, 915 OSCC patients were enrolled. MPOC incidence and characteristics were analyzed. CBQ and other risk factors for MPOC were investigated by chi-squared test and logistic stepwise regression analysis.

Among 915 patients, 15 were diagnosed with synchronous MPOC. After follow-up, 60 of 915 patients developed a second or third primary lesion site and were diagnosed with metachronous MPOC. The remaining 840 patients were then diagnosed with single primary oral cancer (SPOC). The cumulative incidence of MPOC in all OSCC patients was 8.2%. CBQ and the related oral submucous fibrosis (OSF) were found to be independent risk factors of MPOC (P < 0.001). Both MPOC and SPOC patients with a CBQ habit were much younger than those who did not have a CBQ habit (P < 0.001). The buccal mucosa was the most common primary occurrence site (35.9%) in MPOC cases, and almost all MPOC patients with buccal cancer had previously suffered from OSF (88.9%).

CBQ and CBQ-related OSF, for the first time, are identified as the independent risk factors of MPOC. Prevention and treatment of OSF as well as cessation of CBQ are expected to become new approaches to reduce the incidence of MPOC.

More frequent physical examinations should be undertaken in OSCC patients with CBQ or CBQ-related OSF.