Most cases of oral squamous cell carcinoma (OSCC) develop from visible oral potentially malignant disorders (OPMDs). The latter exhibit heterogeneous subtypes with different transformation potentials, complicating the early detection of OSCC during routine visual oral cancer screenings. To develop clinically applicable biomarkers, we collected saliva samples from 96 healthy controls, 103 low-risk OPMDs, 130 high-risk OPMDs, and 131 OSCC subjects. These individuals were enrolled in Taiwan’s Oral Cancer Screening Program. We identified 302 protein biomarkers reported in the literature and/or through in-house studies and prioritized 49 proteins for quantification in the saliva samples using multiple reaction monitoring-MS. Twenty-eight proteins were successfully quantified with high confidence. The quantification data from non-OSCC subjects (healthy controls + low-risk OPMDs) and OSCC subjects in the training set were subjected to classification and regression tree analyses, through which we generated a four-protein panel consisting of MMP1, KNG1, ANXA2, and HSPA5. A risk-score scheme was established, and the panel showed high sensitivity (87.5%) and specificity (80.5%) in the test set to distinguish OSCC samples from non-OSCC samples. The risk score >0.4 detected 84% (42/50) of the stage I OSCCs and a significant portion (42%) of the high-risk OPMDs. Moreover, among 88 high-risk OPMD patients with available follow-up results, 18 developed OSCC within 5 y; of them, 77.8% (14/18) had risk scores >0.4. Our four-protein panel may therefore offer a clinically effective tool for detecting OSCC and monitoring high-risk OPMDs through a readily available biofluid.

Oral cancer is one of the most common cancers worldwide, and there are currently no biomarkers approved for aiding its management. Although many potential oral cancer biomarkers have been discovered, very few have been verified in body fluid specimens in parallel to evaluate their clinical utility. The lack of appropriate multiplexed assays for chosen targets represents one of the bottlenecks to achieving this goal. In the present study, we develop a peptide immunoaffinity enrichment-coupled multiple reaction monitoring-mass spectrometry (SISCAPA-MRM) assay for verifying multiple reported oral cancer biomarkers in saliva. We successfully produced 363 clones of mouse anti-peptide monoclonal antibodies (mAbs) against 36 of 49 selected targets, and characterized useful mAbs against 24 targets in terms of their binding affinity for peptide antigens and immuno-capture ability. Comparative analyses revealed that an equilibrium dissociation constant ( ) cut-off value < 2.82 × 10 m could identify most clones with an immuno-capture recovery rate >5%. Using these mAbs, we assembled a 24-plex SISCAPA-MRM assay and optimized assay conditions in a 25-μg saliva matrix background. This multiplexed assay showed reasonable precision (median coefficient of variation, 7.16 to 32.09%), with lower limits of quantitation (LLOQ) of <10, 10-50, and >50 ng/ml for 14, 7 and 3 targets, respectively. When applied to a model saliva sample pooled from oral cancer patients, this assay could detect 19 targets at higher salivary levels than their LLOQs. Finally, we demonstrated the utility of this assay for quantification of multiple targets in individual saliva samples (20 healthy donors and 21 oral cancer patients), showing that levels of six targets were significantly altered in cancer compared with the control group. We propose that this assay could be used in future studies to compare the clinical utility of multiple oral cancer biomarker candidates in a large cohort of saliva samples.

Background and Aim The aim of this study is to identify gastric cancer burden in Indigenous Taiwanese peoples and conduct a project to evaluate how to reduce the disparities most effectively in Indigenous communities. Methods First, we quantified the health disparities in gastric cancer in Indigenous peoples using data from the cancer registries during the period of 2006–2014. Second, we identified parameters that might be associated with Helicobacter pylori infection or help identify a good eradication strategy. Results Gastric cancer incidence (24.4 vs 12.3 per 100 000 person‐years) and mortality rates (15.8 vs 6.8 per 100 000 person‐years) were higher in Indigenous than in non‐Indigenous, with 2.19‐fold (95% confidence interval [CI]: 2.06–2.33) and 2.47‐fold (2.28–2.67) increased risk, respectively. In Indigenous communities, H. pylori infection was more prevalent in Indigenous than in non‐Indigenous (59.4% vs 31.5%, P < 0.01). Regression analyses consistently showed that either the mountain or plain Indigenous had 1.89‐fold (95% CI: 1.34–2.66) and 1.73‐fold (95% CI: 1.24–2.41) increased risk for H. pylori infection, respectively, as compared with non‐Indigenous, adjusting for other baseline characteristics. The high infection rates were similarly seen in young, middle‐aged, and older adults. Program eradication rates using clarithromycin‐based triple therapy were suboptimal (73.7%, 95% CI: 70.0–77.4%); the habits of smoking (1.70‐fold, 95% CI: 1.01–2.39) and betel nut chewing (1.54‐fold, 95% CI: 0.93–2.16) were associated with the higher risk of treatment failure. Conclusion Gastric cancer burden is higher in Indigenous Taiwanese peoples than in their non‐Indigenous counterparts. Eliminating the prevalent risk factor of H. pylori infection is a top priority to reduce this health disparity.

The government could improve the screening rate by training case managers to assist in following patients until they complete colonoscopy, subsidizing sedated colonoscopies, and providing health education not only to the general public but also to physicians. Cancer 2018;124:907-15. © 2017 American Cancer Society.

Background and study aims: The likelihood of advanced or synchronous neoplasms is significantly higher in fecal immunochemical test (FIT)-positive subjects than in the general population. The magnitude of colonoscopy-related complication rate in FIT-positive subjects, however, remains unknown. This study aims to elucidate the colonoscopy-related complication rate after positive FIT and compared with colonoscopy performed for other purposes. Patients and methods: Information regarding colonoscopy after positive FIT (FIT-colonoscopy) and ordinary colonoscopy related severe complications during 2010-2014 was ascertained from the Taiwanese Colorectal Cancer (CRC) Screening Program Database and National Health Insurance Research Database (NHIRD). Severe complications included significant bleeding, perforation, and cardiopulmonary events <14 days of colonoscopy. The number of events per 1000 procedures was used to quantify complication rates. Multivariate analysis was conducted to assess the association of various factors with severe complications in comparison with ordinary colonoscopy. Results: A total of 319,114 FIT-colonoscopies (214,955 subjects) were identified. Of those, 51,242 (16.1%) underwent biopsy and 94,172 (29.5%) underwent polypectomy; 2,125 had significant bleeding (6.7‰) and 277 had perforation (0.9‰) <14 days after colonoscopy. Polypectomy, antiplatelet use, and anticoagulant use were associated with higher risk of complications [adjusted odds ratio (aOR)= 4.41 (95% Confidence Interval {CI}=4.05–4.81); 1.35 (95%CI=1.12–1.53); and 1.88 (95%CI=0.61–5.84), respectively]. Compared with ordinary colonoscopy, FIT-colonoscopy involved significantly higher risk of significant bleeding [aOR= 3.10 (95%CI=2.90–3.32)]. Conclusions: FIT-colonoscopy was associated with more than two-fold risk of significant bleeding, especially when polypectomy is performed.