An in vitro model and the underlying pathways of sinonasal inverted papilloma development.

Recently, the specific association between Sinonasal inverted papilloma (SIP) and EGFR exon 20 mutations has been reported. To investigate the link between specific EGFR mutations and SIP development, we established organotypic raft culture system using nasal polyp-derived immortalized NP2 (iNP2) cells expressing EGFR exon 20 mutants or an exon 19 mutant, and SIP-derived iIP4 cells harboring P772_H773insPYNP mutation. In the raft culture, iIP4 cells showed the inverted growth pattern characteristic to SIP. Interestingly, iNP2 cells expressing EGFR exon 20 duplication mutants, S768_D770dup and N771_H773dup, but not of EGFR exon 19 mutant, E746_A750del, showed the inverted growth pattern. Enhanced activation of the PI3K/AKT signaling pathway was observed in iNP2_S768_D770dup and iIP4 cells, while increased MAPK signaling was found in iNP2_N771_H773dup. Increased cell migration and invasion were found in all cells carrying EGFR mutations when compared to iNP2 cells, and this effect was inhibited by either PI3K or MEK inhibitor. Notably, iNP2 cells expressing the N771_H773dup mutant showed the highest migration and invasion abilities. These results suggest that specific mutations in EGFR exon 20 play a crucial role in SIP development, partially though hyper-activation of the PI3K/AKT and MAPK signaling pathways. This study presents the first in vitro model for SIP development, which could facilitate further investigations into SIP pathogenesis and preclinical studies for new therapeutic agents.

Human Papillomavirus 16 E6 Suppresses Transporter Associated with Antigen-Processing Complex in Human Tongue Keratinocyte Cells by Activating Lymphotoxin Pathway.

Infection by high-risk human papillomaviruses (hrHPVs), including HPV type 16 (HPV16), is a major risk factor for oral squamous cell carcinomas (OSCCs). However, the pathogenic mechanism by which hrHPVs promote oral carcinogenesis remains to be elucidated. Here, we demonstrated that the suppression of a transporter associated with the antigen-processing complex (TAPs; TAP1 and TAP2), which is a key molecule in the transportation of viral antigenic peptides into MHC class-I cells, is affected by the E6 protein of HPV16. Mechanistically, HPV-mediated immune evasion is principally mediated via the signal-transduction network of a lymphotoxin (LT) pathway, in particular LTα1ß2 and LTßR. Our analysis of transcriptomic data from an HNSCC cohort from the Cancer Genome Atlas (TCGA) indicated that expression of TAP genes, particularly TAP2, was downregulated in HPV-infected cases. We further demonstrated that LTα1ß2 and LTßR were upregulated, which was negatively correlated with TAP1 and TAP2 expression in HPV-positive clinical OSCC samples. Taken together, our findings imply that HPV16 E6 regulates the machinery of the antigenic peptide-loading system and helps to clarify the role of oncogenic viruses in the context of oral carcinoma.

Association of Human Papillomavirus and Epstein-Barr Virus Infection with Tonsil Cancer in Northeastern Thailand.

BACKGROUND: Human papillomavirus (HPV) and Epstein-Barr virus (EBV) are associated with head and neck cancer, including tonsil cancer (TC) in the oropharyngeal area. Increasing incidence of HPV and EBV infection in different cancer tissues of oropharynx in both epithelial and lymphoid tissues, have been reported. However, little is known about association of these tumor viruses with TC in the Thai population. Here, we investigated the prevalence of HPV and EBV infection in different histology of TC and their association with TC from Thai patients. METHODS: Eighty-three exfoliated tonsil cells from non-cancer controls (NCC) and 65 formalin-fixed paraffin-embedded TC tissues (TC) that were histologically classified as tonsillar squamous-cell carcinoma (TSCC) or diffuse large B-cell lymphoma (DLBCL) were studied. Prevalence of HPV and EBV infection was determined by real-time PCR. HPV genotyping was performed by reverse line blot hybridization and HPV genome status was investigated by multiplex qPCR. Localization of EBV infection was determined by EBER in situ hybridization. RESULTS: Infection of HPV and EBV in TC cases was 16.9% and 30.8%, whereas in exfoliated tonsil cells was 1.2% and 66.3% respectively. HPV infection was significantly higher in TSCC (30.6%) than DLBCL samples (13.8%). HPV58 was commonly detected and presented as an integrated form in TSCC, whereas only episomal form was found in DLBCL. EBV infection was significantly higher in DLBCL (44.8%) than TSCC samples (19.4%), and detected in both lower than among exfoliated tonsil cell samples (66.3%). By EBER in situ hybridization in TSCC, EBV infection localized both in epithelial cells and infiltrating lymphocytes. The co-occurrence of HPV and EBV infection was 11.11% and 13.79% of TSCC and DLBCL, respectively, was associated with well-differentiated TSCC. CONCLUSION: HPV and EBV infection was significantly involved in a specific TC tissue, and associated with a good clinical outcome in TSCC.

Barriers to early detection and management of oral cancer in the Asia Pacific region.

OBJECTIVE: Oral cancer is amenable to early detection but remains a prominent cause of mortality in the Asia Pacific region. This study aimed to identify barriers to early detection and management of oral cancer in the Asia Pacific region. METHODS: A mixed-methods approach was employed triangulating findings from a survey and focus groups. The survey was conducted among seven representative members of the Asia Pacific Oral Cancer Network (APOCNET) across six countries. Focus groups were conducted to gain deeper insights into the findings of the survey. RESULTS: The identified barriers were a lack of national cancer control strategies and cancer registries and the limited availability of trained health care professionals. Overcoming these challenges in the Asia Pacific region where resources are scarce will require collaborative partnerships in data collection and novel approaches for continuous professional training including eLearning. Further, to overcome the lack of trained health care professionals, innovative approaches to the management of oral potentially malignant lesions and oral cancer including telemedicine were suggested. CONCLUSION: The findings of this study should be taken into account when charting national cancer control plans for oral cancer and will form the basis for future collaborative studies in evaluating effective measures to improve oral cancer detection and management in low- and middle-income countries.

"Endoscopy Salon" for Controlling Respiratory Droplet Spreading During Endoscopic Procedure.

Introduction Preventing droplet dispersal is an important issue for decreasing the coronavirus 2019 (COVID-19) transmission rate; numerous personal protective equipment (PPE) devices have been recently developed for this. Objective To evaluate the effectiveness of a novel PPE device to prevent droplet spread during nasal endoscopic and fiber optic laryngoscopic examination and postuse equipment cleaning technique. Methods The "endoscopy salon" was created with a hooded salon hair dryer, plastic sheath, and silicone nipple. Comparison fluorescence dye dispersal from simulating forceful coughing with and without using the "endoscopy salon" was conducted to assess the droplet spread control. The effects of heat produced in the "endoscopy salon" and disinfection cleaning were also evaluated. Results Fluorescent dye droplet spread from a mannequin's mouth without using the "endoscopy salon" to care providers' clothes and the floor surrounding mannequin, whereas no dye droplets spread out when using the "endoscopy salon". The maximal temperature observed in the hair dryer was 56.3°C. During the cleaning process, when a plastic bag was attached to the hair dryer's hood to create a closed system, the temperature increased to 79.8 ± 3.1 °C. These temperatures eliminated four test organism cultures during equipment disinfection. Conclusion This novel "endoscopy salon" device prevented respiratory droplet spread and eliminated infectious organisms during postuse equipment cleaning.

Establishment and genetic characterization of cell lines derived from proliferating nasal polyps and sinonasal inverted papillomas.

To better understand the pathogenesis of nasal polyps (NPs) and sinonasal inverted papillomas (SIPs), we aimed to establish cell lines from fresh tissues of NPs and SIPs and characterize them. Primary cell cultures were obtained from two NP tissues (NP2 and NP3) and one SIP tissue (IP4). All the cells were polygonal in shape, expressed cytokeratin 14, and had normal diploid chromosome status. HPV58 DNA was detected in NP3. To obtain immortal primary cells, NP2 and IP4 cells were transduced with a combination of mutant CDK4, cyclinD1 and TERT. These cells were thereafter named NP2/K4DT and IP4/K4DT, respectively. HPV58-positive NP3 cells were transduced with TERT alone, the resulting cells named NP3/T. Phenotypic and genotypic identity of original tissues and derived cells was investigated. All the cell cultures with transgenes were confirmed to be derived from their parental cells and primary tumor tissues by analysis of short tandem repeats (STR) and maintained in vitro growth, genetic profiles and gene expression characteristics of the primary cells. These virtually immortalized cells, as well as the primary cells, have potential as in vitro models for studying the pathogenesis of NPs and SIPs and for preclinical study to develop new therapeutic agents.

Survival of Cancer Patients with Co-Morbid Tuberculosis in Thailand.

BACKGROUND AND OBJECTIVE: We aimed to investigate the survival time and its related factors among cancer patients with co-morbid tuberculosis (TB) in Thailand. METHODS: We conducted this retro-prospective cohort study on cancer patients without co-morbid TB using the data from population-based cancer registry of Khon Kaen, TB databases from the Khon Kaen Central Hospital, and the Region 7 Office of Disease Prevention and Control from 2001 to 2015 to determine the onset of TB after cancer. The cancer patients were then followed up until 2017 to assess their survival status. The Kaplan-Meier method, log-rank test, and Cox proportional hazard regression were used to estimate cumulative survival curves, compare various survival distributions, and adjusted hazard ratios. RESULTS: Lung, head and neck, and liver cancers led to a  significantly different survival time between patients with and without co-morbid TB. After adjustment, it was found that patients suffering from lung, head and neck, or liver cancer and co-morbid TB had significantly lower risk of death than those without co-morbid TB. Based on the stratified analysis, lung cancer patients with distant metastasis and co-morbid TB had 3.01-fold and 2.99-fold significantly increased risk of death compared to those without co-morbid TB. CONCLUSION: We found that cancer patients with co-morbid TB were at lower risk of death compared with those without co-morbid TB. In addition to cancer stage, it seems that cancer comorbidity with TB could modify the risk of death for lung cancer patients.There is a need for further studies to support our findings including other related risk factors. 
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Effectiveness of a programable body-worn digital hearing aid for older adults in a developing country: a randomized controlled trial with a cross-over design.

BACKGROUND: Hearing aids are important assistive devices for hearing rehabilitation. However, the cost of commonly available commercial hearing aids is often higher than the average monthly income of individuals in some developing countries. Therefore, there is a great need to locally produce cheaper, but still effective, hearing aids. The Thai-produced P02 hearing aid was designed to meet this requirement. OBJECTIVE: To compare the effectiveness of the P02 hearing aid with two common commercially available digital hearing aids (Clip-II™ and Concerto Basic®). METHODS: A prospective, randomized controlled trial with a cross-over design was conducted from October 2012 to September 2014 in a rural Thai community. There were 73 participants (mean age of 73.7 ± 7.3 years) included in this study with moderate to severe hearing loss who were assessed for hearing aid performance, including probe microphone real-ear measurement, functional gain, speech discrimination, and participant satisfaction with the overall quality of perceived sound and the design of the device. RESULTS: There were no statistically significant differences in functional gain or speech discrimination among the three hearing aids evaluated (p-value > 0.05). Real-ear measurements of the three hearing aids met the target curve in 93% of the participants. The best real-ear measurement of the hearing aid following the target curve was significantly lower than that of Clip-II™ and Concerto Basic® (p-value < 0.05) at high frequency. However, participants rated the overall quality of sound higher for the P02 hearing aid than that of Clip-II™ but lower than that of Concerto Basic® (p-value > 0.05). Participants revealed that the P02 hearing aid provided the highest satisfaction ratings for design and user-friendliness with statistical significance (p-value < 0.05). CONCLUSION: The P02 hearing aid was an effective device for older Thai adults with hearing disabilities. Additionally, its modern design, simplicity of use, and ease of maintenance were attractive to this group of individuals. These benefits support the rehabilitation potential of this hearing aid model and its positive impact on the quality of life of older adults in developing countries. TRIAL REGISTRATION: This study was registered under Clinicaltrial.gov NCT01902914 . Date of registration: July 18, 2013.

Survival Benefit of Intervention Treatment in Advanced Anaplastic Thyroid Cancer.

BACKGROUND: The management of anaplastic thyroid cancer (ATC) is controversial; thus, proper treatment and prognostic factors should be investigated. OBJECTIVES: To compare the survival outcomes of the intervention and palliative treatment in ATC patients. METHODS: A hospital-based retrospective study was conducted at a single tertiary university hospital. The medical record charts were retrieved from November 20, 1987, to December 31, 2016. The final follow-up ended by December 31, 2017. The patients' demographic data, laboratory data, clinical presentation, and treatment modality results were analyzed. RESULTS: One hundred twenty-one records were analyzed with a one-year overall survival rate of 3.5% (median survival time: 77 days); however, 16 cases had insufficient data to classify staging and treatment modalities. Therefore, 105 ATC patients (37 with stage IVa, 39 with stage IVb, and 29 with stage IVc disease) were included with a one-year overall survival rate of 4.0% (median survival time of 82 days). Intervention treatment allowed longer median survival times (p < 0.05) and a better survival rate (p < 0.05). Among the interventional treatment groups, postoperative chemoradiation yielded the longest median survival time (187 days) and the highest survival rate (20%) (p < 0.05). The intervention modality allowed a better median survival time at all stages, particularly in stage IVa (p < 0.05). Unfavorable prognostic factors were adjusted for in a multiple Cox regression model showing that significant factors included age ≥65 years (hazard ratio HR: 2.57), palliative treatment (HR: 1.85), and leukocytosis ≥10,000 cells/mm3 (HR: 2.76). CONCLUSIONS: Intervention treatment provided a better survival outcome in all stages, particularly in stage IVa, with a significantly better median survival time. Among interventional treatments, postoperative chemoradiation led to the longest survival rate, suggesting that this treatment should be considered in ATC patients with resectable tumors and no poor prognostic factors, such as older age and leukocytosis.

Exosomes-carrying Epstein-Barr virus-encoded small RNA-1 induces indoleamine 2, 3-dioxygenase expression in tumor-infiltrating macrophages of oral squamous-cell carcinomas and suppresses T-cell activity by activating RIG-I/IL-6/TNF-α pathway.

OBJECTIVES: Although exosomes carrying Epstein-Barr virus-encoded small RNA-1 (EBER-1) are involved in the immunosuppressive tumor microenvironments of EBV-associated head and neck carcinomas, the effects of EBER-1-associated exosomes on tumor-infiltrating macrophages are poorly understood. MATERIALS AND METHODS: The association between EBV infection and expression of indoleamine 2,3-dioxygenase (IDO) was assessed in 165 paraffin-embedded oral squamous cell carcinoma (OSCC) tissue samples. Using in vitro techniques, we investigated whether stimulation of the RIG-I/IL-6/TNF-α pathway by exosomes carrying EBER-1 is critical for IDO induction in macrophages. We performed a thymidine incorporation and a cell cytolytic assay to test for up-regulated IDO in macrophages that can block the proliferation and function of effector T cells. RESULTS: Some infiltrated macrophages expressed levels of IDO higher than OSCC cells which was significantly associated with presence of EBV. The production of IDO, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in human monocyte-derived macrophages (MDMs) was induced by EBV-associated exosomes in vitro. Mechanistically, the retinoic acid-inducible gene I (RIG-I) pathway in MDMs was stimulated by EBV-encoded small RNA-1 (EBER-1) whereas the inhibition of these pathways by BX-795 almost abolished the production of these two cytokines and IDO induction. Also, the EBER-1-activated IDO in MDMs suppressed the proliferation of T lymphocytes and diminished the cytolytic activity of CD8+ T cells. CONCLUSION: Exosomes carrying EBER-1 could induce IDO expression in MDMs, considerably aided by an IL-6 and TNF-α-dependent mechanism via the RIG-I signaling pathway, which might create an immunosuppressive microenvironment affecting T-cell immune responses.

Is Adjunctive Hyperbaric Oxygen Treatment Alone or with Surgery the Proper Management for Active and Persistent Osteoradionecrosis?

ABSTRACT: This study enrolled patients with stage 3 osteoradionecrosis. There were three treatment modalities: antibiotics, hyperbaric oxygen therapy (HBOT), and surgery. Complete healing was the primary outcome. Multiple logistic regression analysis demonstrated that surgery with HBOT improved wound healing better than HBOT alone.

Sinus and anterior skull base surgery during the COVID-19 pandemic: systematic review, synthesis and YO-IFOS position.

PURPOSE: The COVID-19 pandemic has caused significant confusion about healthcare providers' and patients' pandemic-specific risks related to surgery. The aim of this systematic review is to summarize recommendations for sinus and anterior skull base surgery during the COVID-19 pandemic. METHODS: PubMed/MEDLINE, Google Scholar, Scopus and Embase were searched by two independent otolaryngologists from the Young Otolaryngologists of IFOS (YO-IFOS) for studies dealing with sinus and skull base surgery during COVID-19 pandemic. The review also included unpublished guidelines edited by Otolaryngology-Head and Neck Surgery or Neurosurgery societies. Perioperative factors were investigated including surgical indications, preoperative testing of patients, practical management in operating rooms, technical aspects of surgery and postoperative management. The literature review was performed according to PRISMA guidelines. The criteria for considering studies or guidelines for the review were based on the population, intervention, comparison, outcome, timing and setting (PICOTS) framework. RESULTS: 15 International publications met inclusion criteria. Five references were guidelines from national societies. All guidelines recommended postponing elective surgeries. An algorithm is proposed that classifies endonasal surgical procedures into three groups based on the risk of postponing surgery. Patients' COVID-19 status should be preoperatively assessed. Highest level of personal protective equipment (PPE) is recommended, and the use of high-speed powered devices should be avoided. Face-to-face postoperative visits must be limited. CONCLUSIONS: Sinus and skull base surgeries are high-risk procedures due to potential aerosolization of SARS-CoV-2 virus. Protection of health care workers by decreasing exposure and optimizing the use of PPE is essential with sinus and anterior skull base surgery.

Epstein-Barr Virus-Associated Langerhans Cell Histiocytosis of the Thyroid Gland.

Thyroid gland involvement of Langerhans cell histiocytosis (LCH) is extremely rare in both systemic and isolated disease. The role of viral infection in LCH development is not yet fully understood. Although several viruses are proposed as etiologic factors, such as Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6), they seem to play a bystander role in LCH. A 29-year old female patient with a prior history of multisystemic LCH (pituitary gland and skull bone), presented with a thyroid nodule. The patient underwent a total thyroidectomy and the histological examination revealed nodular lesions composed of sheets and clusters of histiocytes in the inflammatory background. The histiocytes stained positive for S-100 and CD1a and were negative for HHV-8, cytomegalovirus, and VE1 (anti-BRAFV600E) on immunohistochemistry. The EBER in situ hybridization for EBV showed frequent positive-stained cells. The conventional PCR analysis for EBV was positive and qPCR analysis confirmed a significant DNA copy number difference (p = 0.02) between the tumor and adjacent non-neoplastic thyroid tissue. PCR analysis for HHV-6, HPV, HSV was negative in both tumor and benign samples. In conclusion, the presented case showed a rare thyroid involvement by LCH associated with EBV infection, which has not been reported before. Further studies are required to investigate a possible etiologic link between EBV infection and LCH.

A Three-arm, Single-blind, Randomized Controlled Trial Examining the Effects of Notched Music Therapy, Conventional Music Therapy, and Counseling on Tinnitus.

OBJECTIVE: To compare the efficacy of three common interventions for tinnitus patients: notched music therapy, conventional music therapy, and counseling. STUDY DESIGN: Randomized, single-blinded, controlled, three-arm trial. METHOD: This study was conducted from January 2018 to January 2019. Eligible subjects were randomized into three groups. The first group received notched music therapy (n = 25), the second received conventional music therapy (n = 24), and the third received counseling only (n = 26). The three groups did not differ in terms of demographic data including age, sex, tinnitus duration, affected side, hearing level, side of tinnitus, and frequency of tinnitus. The patients were followed up on at month 1, 2, and 3 after initiation of therapy. RESULTS: Tinnitus Handicap Inventory scores gradually decreased in all groups. The mean differences in Tinnitus Handicap Inventory score from baseline for patients who received notched music therapy, conventional music therapy, and counseling only were 20.49, 27.83, and 17.79 points, respectively (p < 0.05). However, there was no statistically significant difference among the groups (p = 0.246). CONCLUSION: There was no difference between the treatments. The selection of these therapies for tinnitus treatment may depend on the unique needs and proclivities of patients. TRIAL REGISTRATION: clinicaltrials.in.th/TCTR20180225002.

Peroxiredoxin 2 is highly expressed in human oral squamous cell carcinoma cells and is upregulated by human papillomavirus oncoproteins and arecoline, promoting proliferation.

Peroxiredoxin 2 (PRDX2) is upregulated in various cancers including oral squamous cell carcinoma (OSCC). It is a known tumor promoter in some cancers, but its role in OSCC is unclear. This study aimed to investigate the effect of arecoline, an alkaloid of the betel nut, and human papillomavirus type 16 (HPV16) E6/E7 oncoproteins on induction of PRDX2 expression, and also the effects of PRDX2 overexpression in oral cell lines. Levels of PRDX2 protein were determined using western blot analysis of samples of exfoliated normal oral cells (n = 75) and oral lesion cells from OSCC cases (n = 75). Some OSCC cases were positive for HPV infection and some patients had a history of betel quid chewing. To explore the level of PRDX2 by western blot, the proteins were extracted from oral cell lines that were treated with arecoline or retroviruses containing HPV16 E6 gene and HPV16 E6/E7 expressing vector. For analysis of PRDX2 functions, cell proliferation, cell-cycle progression, apoptosis and migration was compared between oral cells overexpressing PRDX2 and cells with PRDX2-knockdown. PRDX2 expression levels tended to be higher in OSCC samples that were positive for HPV infection and had history of betel quid chewing. Arecoline treatment in vitro at low concentrations and overexpression of HPV16 E6 or E6/E7 in oral cells induced PRDX2 overexpression. Interestingly, in oral cells, PRDX2 promoted cell proliferation, cell-cycle progression (G2/M phase), cell migration and inhibited apoptosis. Upregulation of PRDX2 in oral cells was induced by arecoline and HPV16 oncoproteins and promoted growth of OSCC cells.

Subtype Specific Nasopharyngeal Carcinoma Incidence and Survival Trends: Differences between Endemic and Non-Endemic Populations.

BACKGROUND: While nasopharyngeal carcinoma (NPC) is rare in non-endemic regions such as the North America, endemic countries, such as Thailand, continue to struggle with high incidence and mortality rates. NPC has a complex etiology that varies by histological subtype. METHODS: NPC cases (1990-2014) were identified using the International Classification of Diseases for Oncology (ICD-O) code C11 from the Chiang Mai, Khon Kaen, Lampang, and Songkhla cancer registries and compared to Asian/Pacific Islanders (A/PI) from the US SEER program. Age-standardized incidence rates and changes in annual percent change (APC) for overall and subtype specific NPC were assessed using R and Joinpoint. Kaplan Meier curves were generated in SAS to evaluate differences in survival by sex, year of diagnosis and histological subtype. Five-year relative survival estimates were calculated between 2000-2014. RESULTS: Non-keratinizing NPC predominated across all registries except Songkhla, where the keretinizing subtype made up ~60% of all reported cases. Incidence of keratinizing NPC significantly decreased among Chiang Mai males between 1996 and 2014 (APC:-13.0 [95%CI:-16.2, -9.6]), Songkhla females (APC:-4.0 [95%CI: -7.4, -0.5]) and males between 2006 and 2014 (APC:-15.5 [95%CI:-25.0, -4.7]), as well as A/PI females (APC:-5.1 [95%CI:-6,7, -3.4]) and males (APC: -4.8 [95%CI:-5.9, -3.7]). Non-keratinizing NPC increased among Songkhla males (APC:4.3 [95%CI:1.8, 6.9]). The keratinizing subtype exhibited the worst survival, while the non-keratinizing undifferentiated subtype had the best survival. Although US A/PI had the highest 5-year relative survival estimates, among the Thai registries Chiang Mai had the best and Lampang the worst survival. CONCLUSION: Although US A/PIs exhibited similar rates of NPC as seen in the endemic Thai population, improved tobacco control has led to a decrease in keratinizing NPC incidence irrespective of geography. Additionally, while challenges associate with access to care may still exist among rural Thais, chemoradiation was shown to confer a survival benefit in non-keratinizing NPC treatment.

Sex Differences in the Heterogeneous Dynamic Incidence of Oral Cancer: A Comparison between Taiwan and Thailand.

BACKGROUND: This study aims at investigating differences in oral cancer (OC) incidence trends between two populations in Taiwan and Thailand. METHODS: We used the population-based cancer registry data from Taiwan (1979-2016) and Khon Kaen (KK), Thailand (1985-2016). We performed joinpoint analyses to detect the trend change points for the OC incidence and to quantify the time trends in both sexes and regions. Age-period-cohort curves were plotted to explain the incidence trends. RESULTS: In Taiwan, the estimated annual increases in OC were approximately 6.0% in males, although the increase slowed after 2009, and 2.6% in females. In KK, the OC incidence steadily decreased by -2.5% per year in females, but there was no obvious change in males. A strong period effect observed in those aged 45-69 years in Taiwanese males resulted in a peak incidence in the middle age group. Decreased period and cohort effects were observed in females in KK. CONCLUSIONS: Taiwanese males are the predominant sex affected by OC in Taiwan, and the trend has decelerated since 2009. Age, period, and cohort effects were different between males and females in the two regions.

Incidence of and Risk Factors for Tuberculosis among Cancer Patients in Endemic Area: A Regional Cohort Study.

BACKGROUND AND OBJECTIVE: Cancer is a known risk factor for developing active tuberculosis (TB) disease. The incidence of and risk factors for TB are not known among cancer patients in Thailand. This study aimed to investigate risk factors for TB among cancer patients in an area with endemic TB infections. METHODS: We used the Khon Kaen population-based cancer registry and two TB databases to conduct a retrospective cohort study of cancer patients. From 2001 to 2015, we identified 40,948 eligible cancer patients. Following until 2017, we identified cases of TB diagnosed after cancer diagnosis and analyzed primary cancer site, staging, treatment, and demographic factors. Adjusted incidence rate ratios (adj. IRR) were computed to identify risk factors among a sub-set of cancer types (n = 9,733) using Poisson regression. RESULTS: Among all cancer patients, 472 cases of TB were diagnosed following cancer diagnosis (cumulative incidence = 1.15%, incidence rate = 421.86 cases per 100,000 patients per year). Among the sub-set of cancer types, 206 cases of TB were found (cumulative incidence = 2.11%, incidence rate = 848.26 cases per 100,000 patients per year). Risk factors for TB among cancer patients were sex (p < 0.001) (male adj. IRR  = 1.87, 95% CI: 1.36-2.59), age (p < 0.001) (age >70 adj. IRR  = 2.36, 95% CI: 1.56-3.55, compared to age ≤50) and cancer site (p < 0.001). Compared to thyroid cancer, TB infection was more associated with lung cancer without histopathological confirmation (adj. IRR  = 6.22, 95% CI: 2.57-15.04). Cancer stage and treatment did not show statistically significant trends. CONCLUSION: Old age, male sex, and certain cancer types were independent risk factors for TB in cancer patients. Targeted latent TB screening may be appropriate among high risk groups.