Effect of esophageal cancer screening on mortality among patients with oral cancer and second primary esophageal cancer in Taiwan

Age-standardized incidence and mortality related to oral and esophageal cancers worldwide are 6.3 per 100,000 and 5.6 per 100,000, respectively, and even greater in Asian countries [1]. The trend in incidence of oral and esophageal cancers rose 1.7 and 1.6 times, respectively, from 1998 to 2018 in Taiwan, in particular among men [2]. Oral and esophageal cancers are the fourth and fifth leading causes of cancer deaths among men in Taiwan [3]. Huang et al. (2020) estimated economic burdens related to cancer for 2007–2017 in Taiwan and found that direct medical costs and indirect costs for esophageal cancer accounted for USD 19,816 and USD 60,693 due to mortality; oral cancer accounted for USD 19,644 and USD 35,570. Both cancers ranked in the top three of the ten most costly cancers in Taiwan [4].

Risk of developing second primary esophageal cancer (SPEC) is higher for patients with oral cavity cancer (OCC) than for the general population [5], [6]. Over 50 % of head and neck cancer (HNC) patients developing SPEC have been diagnosed with OCC in Taiwan [7], [8]. Furthermore, OCC is the most common type of HNC in Taiwan, and the number of OCC cases is higher than the numbers of oropharynx and hypopharynx cancer cases [6], [9]. The major histological type for both OCC and SPEC is squamous cell carcinoma (SCC) in Asian countries. Oral SCC and esophageal SCC share a common carcinogenic pathway of mucosal exposure to alcohol, smoking, and betel nuts [10]. These three factors trigger carcinogenesis along the upper aerodigestive tract at different sites. Second malignancies develop near the primary cancer site, a phenomenon called “field cancerization” [11].

Survival rates are worse for OCC patients with SPEC, despite a good prognosis for OCC [9]. In a hospital-based study evaluating survival rates for head and neck SCC patients, 5-year survival for those who developed esophageal high-grade or SCC was significantly lower than for those without esophageal neoplasms (37.1 % v.s.71.6 %, P < 0.0001). Survival was worse for those with higher grade esophageal neoplasms [12]. Previous population-based studies in Taiwan showed that the median survival times from the diagnosis dates of primary OCC and SPEC were 5.32 and 0.73 years, respectively [6], [9]. Thus, SPEC may shorten survival time by almost 5 years among OCC patients. Misconstruing dysphagia as a side effect caused by OCC treatments and remaining asymptomatic at early stages of esophageal cancer are the main reasons for delays in diagnosing SPEC. Thus, endoscopic screening for esophageal neoplasms is crucial for OCC patients without symptoms of esophageal cancer. The purpose of endoscopic screening is to detect precancerous lesions or early stages of esophageal cancer before the onset of signs and symptoms, and to improve survival among patients with HNC [13], [14]. Image-enhanced endoscopy with high diagnostic accuracy, including Lugol's chromoendoscopy and narrow-band image, is generally used to detect esophageal neoplasms [15], [16], [17], [18].

OCC patients may develop newly diagnosed SPEC within 10 years after the initial OCC diagnosis, and the mean interval between incident OCC and SPEC is 3.10 years [7], [8], [19]. Endoscopic examination may be recommended for head and neck SCC patients as needed in the American Gastroenterological Association Guideline and in the 2011 Oral Cavity Cancer Treatment Guideline, but such recommendation is not mentioned in the 2021 National Comprehensive Cancer Network guideline [20], [21], [22]. A hospital-based study in Taiwan encouraged patients to undergo endoscopic examination in the first 3 years after HNC diagnosis [23]. A review study moderately recommended endoscopic screening every 6 months to 1 year for 10 years [13]. The consensus of guidelines and published studies regarding endoscopic screening strategies to detect SPEC in OCC patients remains controversial.

Most relevant studies in Taiwan investigated the risks and incidence of SPEC among HNC patients undergoing endoscopic examination. For example, one recent study by Ho et al. (2022) compared detection of incident SPEC and the stage-shift effect of endoscopic screening between screened and non-screened incident OCC patients and found that endoscopic screening achieved early detection of SPEC [24]. However, very few studies assessed the survival effect of endoscopic screening among OCC patients who develop SPEC. Two hospital-based studies in Taiwan assessed the relative benefits of endoscopic screening among patients with HNC. Su et al. implied that endoscopic screening improved early detection of SPEC; Chung et al. indicated that survival was better for screened than for non-screened patients [14], [25]. To the best of our knowledge, there is no empirical evidence from a nationwide population-based database to examine this issue among OCC patients with SPEC. Therefore, this study aimed to compare 5-year mortality between endoscopically screened and non-screened patients with newly diagnosed OCC who developed SPEC between 2004 and 2013, using Taiwan's nationwide population-based databases. The study findings may provide empirical evidence regarding the benefit of endoscopic screening exams for early detection and improved survival.

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