Cancer patterns in nasopharyngeal carcinoma multiplex families over 15 years.

BACKGROUND: Genetic and environmental factors are important determinants of nasopharyngeal carcinoma (NPC). NPC is associated with Epstein-Barr virus (EBV) infection. Studies have reported familial aggregation of NPC, but evidence has been mixed for elevated rates of cancers other than NPC. METHODS: The authors reassessed their previous evaluation of familial aggregation of cancer in 348 high-risk Taiwanese multiplex families with 2 or more NPC cases enrolled between 1980 and 2003. Participants were linked to the Taiwan National Cancer Registry and National Death Registry to identify cancers. RESULTS: In all, 2590 individuals contributed 37,959 person-years over an average of 15 years of follow-up; 314 incident cancers were identified. The authors computed multiple primary standardized incidence ratios (MP-SIRs) to evaluate the overall risk and the risk of infection-associated, EBV-associated, and individual cancers. The overall MP-SIR was 1.24 (95% confidence interval [CI], 1.10-1.38). The exclusion of excess NPC risk led to an overall MP-SIR of 1.11 (95% CI, 0.98-1.25). Similarly, the risk of cancers associated with infectious agents was driven by the excess in NPC, and its exclusion led to an MP-SIR of 1.22 (95% CI, 0.99-1.48) for infection-associated cancers and to an MP-SIR of 1.18 (95% CI, 0.72-1.82) for EBV-associated cancers. The authors observed a significant excess of second cancers among NPC cases (oral cancer, mouth cancer, tongue cancer, gum cancer, nasal cavity cancer, bone cancer, and non-Hodgkin lymphoma). CONCLUSIONS: This reassessment of the largest NPC multiplex family study confirms the presence of NPC coaggregation within families in Taiwan but does not provide evidence for a broader familial syndrome involving NPC and other tumors. Among NPC cases, elevated rates of secondary cancers, mostly at the, head and neck and hematopoietic cancers suggest radiation treatment effects on subsequent cancer risk.

Identification of a metastatic lung adenocarcinoma of the palate mucosa through genetic and histopathological analysis: a rare case report and literature review.

BACKGROUND: Cancers of unknown primary origin (CUPs) are reported to be the 3-4th most common causes of cancer death. Recent years have seen advances in mutational analysis and genomics profiling. These advances could improve accuracy of diagnosis of CUPs and might improve the prognosis of patients with CUPs. CASE PRESENTATION: A 76-year old male with an adenocarcinoma of unknown primary origin in the lung presented with another tumor of the palate mucosa. The tumor cells in the pleural effusion were all negative for immunohistochemical markers (TTF-1 and Napsin A) and lung-specific oncogenic driver alterations (EGFR mutation and ALK translocation). The tumor of the palate mucosa was likewise identified as an adenocarcinoma, and the cells showed cytological similarities with the tumor cells in the pleural effusion; TTF-1, Napsin A, EGFR mutation and ALK translocation were all negative. This result suggested that origins of the tumors of the palate mucosa and in the lung were the same, even though the origin had not yet been determined. Next, we addressed whether the tumor of the palate mucosa was a primary tumor or not. Secretory carcinoma (SC), which is a common type of minor salivary gland tumor (MSGT), was suspected; however, mammaglobin was negative and ETV6-NTRK3 (EN) fusion was not observed. Other MSGTs were excluded based on histological and immunohistochemical findings. Furthermore, an additional examination demonstrated an oncogenic KRAS mutation at codon 12 (p.G12D) in both palate tumor and in pleural effusion. KRAS mutation is known to exist in one-third of lung adenocarcinomas (LUADs), but quite rare in MSGTs. The possibility of metastasis from other organs was considered unlikely from the results of endoscopic and imaging studies. This result indicated that the primary site of the CUP was indeed the lung, and that the tumor of the palate mucosa was a metastasis of the LUAD. CONCLUSIONS: A tumor of the palate mucosa that showed diagnostic difficulties was determined to be a metastatic LUAD by genomic alterations and histopathological findings.

Risk for a second primary hypopharyngeal and esophageal cancer after an initial primary oral cancer.

OBJECTIVE: To investigate the risk for second primary cancer in the hypopharynx and esophagus (SPC-HE) among individuals with an initial oral/oropharyngeal cancer. MATERIALS AND METHODS: Mass screening data from Taiwan (2004-2009) included individuals who were ≥18 years old and smoked cigarettes and/or chewed betel quid. Occurrence of SPC-HE was monitored until December 31, 2014. Results were expressed as adjusted relative risk (aRR) and 95% confidence interval (CI). RESULTS: One hundred and fifty-eight out of 4,494 subjects with oral cancer developed SPC-HE (incidence rate: 6.47 per 1,000 person-years). Relative to patients with primary cancers in the lip, the risk of an SPC-HE was higher in patients with primary cancers in oropharynx (aRR: 19.98, 95% CI: 4.72-84.55), floor of mouth (aRR: 12.13, 95% CI: 2.67-55.15), and hard palate (aRR: 7.31, 95% CI: 1.65-32.37), but not in patients with cancers in tongue (aRR: 3.67, 95% CI: 0.89-15.17) or gum (aRR: 3.99, 95% CI: 0.92-17.35). Regression analyses also showed the risk of an SPC-HE was greater in alcohol drinkers than those who did not (aRR: 1.65, 95% CI: 1.10-2.48). CONCLUSIONS: Compared with the initial cancer in the lip, patients with a cancer in the oropharynx, floor of mouth, and hard palate had a higher risk for the SPC-HE.

Prevalence of current oral HPV infection among 100 betel nut chewers or cigarette smokers in Northern Taiwan.

BACKGROUND: The incidence of HPV positive oropharyngeal cancer is increasing in Taiwan. Given this, it is critical to understand the prevalence of oral HPV infection since this cancer is potentially preventable. A community-based study was conducted to evaluate the prevalence of oral HPV infection and sexual behavior changes. METHODS: Between January and December 2016, 100 subjects between 20 and 70 years-old with current/ever betel nut chewing or current cigarette smoking visited the Department of Health, New Taipei City. Subjects with cancer history or known HIV/AIDS were excluded. Sexual behavior information was collected through a questionnaire. Oral rinse samples and oropharyngeal swabs were obtained for HPV genotyping using the EasyChip HPV genotyping array (King-Car, Taiwan). RESULTS: 92 men and 8 women were recruited. The prevalence of oral HPV infection was 3%, present between 60 and 70 (11%) and between 30 and 40 years old (4%). The prevalence of the first sexual contact at younger than 20 years old were 71.4%, 53.6%, 15.4% and 44% in <40, 40-49, 50-59 and 60+ years old, respectively (p for trend = 0.0036). The prevalence of 3 or more lifetime sexual partners were 60.7%, 57.1%, 23.1% and 16.7%, respectively for <40, 40-49, 50-59 and 60+ years old (p for trend = 0.0005). CONCLUSION: The prevalence of oral HPV infection is 3%, in current/ever betel nut chewers or current cigarette smokers in Northern Taiwan. Younger generation have more lifetime sexual partners and younger first sexual contact. This could explain the rising incidence of HPV positive oropharyngeal cancer in Taiwan.

Lifetime risk of distinct upper aerodigestive tract cancers and consumption of alcohol, betel and cigarette.

The cancer of upper aerodigestive tract (UADT) is a common cancers in the world. However, its lifetime risk by consumption of alcohol, betel and cigarettes remain to be elucidated. This study aimed to estimate lifetime risk of distinct UADT cancers and assess their associations with alcohol, betel and cigarette consumption. Three cohorts of 25,611 men were enrolled in 1982-1992 in Taiwan. The history of alcohol, betel and cigarette consumption was enquired through questionnaire interview. Newly developed UADT cancers were ascertained through computerized linkage with national cancer registry profile. Lifetime (30-80 years old) risk and multivariate-adjusted hazard ratio (HRadj) of distinct UADT cancers by alcohol, betel and cigarette consumption were estimated. A total of 269 pathologically confirmed cases of UADT cancers were newly-diagnosed during 472,096 person-years of follow-up. The lifetime risk of UADT cancer was 9.42 and 1.65% for betel chewers and nonchewers, 3.22 and 1.21% for cigarette smokers and nonsmokers and 4.77 and 1.85% for alcohol drinkers and nondrinkers. The HRadj (95% confidence interval) of developing UADT cancer was 3.36 (2.51-4.49), 2.02 (1.43-2.84), 1.90 (1.46-2.49), respectively, for the consumption of betel, cigarette and alcohol. Alcohol, betel and cigarette had different effect on cancers at various anatomical sites of UADT. The cancer risk from the mouth, pharynx, esophagus to larynx increased for alcohol and cigarette consumption, but decreased for betel consumption. Alcohol, betel and cigarette consumption are independent risk predictors for distinct UADT cancers.

The determining risk factors for treatment outcomes in patients with squamous cell carcinoma of the hard palate.

BACKGROUND: The determining risk factors for patients with squamous cell carcinoma of the hard palate are not well verified. METHODS: Medical records from our facility of all patients with squamous cell carcinoma of the hard palate receiving curative surgery between March 2003 and May 2009 were reviewed. RESULTS: Seventy-eight patients were enrolled in the study. The 5 year disease-free and overall survival rates were 49.8 and 49.7%, respectively. The 5 year disease-free and overall survival rates were statistically different between positive/close margins and negative margins (24.6% vs. 65.4%, P = 0.02; 20.1% vs. 63.1%, P = 0.001, respectively), with and without soft palate invasion (38.8% vs. 68.9%, P = 0.02; 27.4% vs. 77.5%, P = 0.001, respectively), and soft palate invasion patients with and without perineural invasion (10.4% vs. 52.8%, P = 0.02; 0% vs. 38.1%, P = 0.008, respectively). The rate of positive nodal metastasis for T3 and T4 tumors was 44%. For the tumor with soft palate invasion, the rate of positive nodal metastasis was 29%. After multivariate analyses, soft palate invasion and positive/close margins were the determining risk factors for disease-free and overall survival. CONCLUSIONS: Soft palate invasion and positive/close margins were the determining risk factors for disease-free and overall survival in patients with squamous cell carcinoma of the hard palate. Elective neck dissection is suggested for advanced primary tumors (T3 or T4) or tumors with soft palate invasion.

Automatic Detection of Oral Lesion Measurement Ruler Toward Computer-Aided Image-Based Oral Cancer Screening.

Intelligent computer-aided algorithms analyzing photographs of various mouth regions can help in reducing the high subjectivity in human assessment of oral lesions. Very often, in the images, a ruler is placed near a suspected lesion to indicate its location and as a physical size reference. In this paper, we compared two deep-learning networks: ResNeSt and ViT, to automatically identify ruler images. Even though the ImageN et 1K dataset contains a "ruler" class label, the pre-trained models showed low sensitivity. After fine-tuning with our data, the two networks achieved high performance on our test set as well as a hold-out test set from a different provider. Heatmaps generated using three saliency methods: GradCam and XRAI for ResNeSt model, and Attention Rollout for ViT model, demonstrate the effectiveness of our technique. Clinical Relevance- This is a pre-processing step in automated visual evaluation for oral cancer screening.

Impact of varying anatomic sites on advanced stage and survival of oral cancer: 9-year prospective cohort of 27 717 cases.

BACKGROUND: To elucidate the impact of varying anatomic sites on advanced stage of and death from oral cancer. METHODS: A total of 27 717 oral cancers mainly from a population-based visual inspection program in Taiwan from 2004 to 2009 was followed until the end of 2012. RESULTS: Using lip cancer as reference, the odds ratios (95% confidence interval [CI]) of advanced stage of cancer were 2.20 (1.92-2.51) for tongue, 2.60 (2.28-2.97) for buccal, 2.68 (2.20-3.28) for floor of mouth, 2.96 (2.52-3.47) for hard palate, 6.04 (5.17-7.05) for gingiva, and 10.83 (9.20-12.74) for oropharynx. The estimated hazard ratios (95% CI) for oral cancer death increased from 1.48 (1.31-1.67) in buccal, 1.61 (1.43-1.82) in tongue, 1.68 (1.41-1.99) in floor of mouth, 1.79 (1.57-2.05) in gingiva, 1.97 (1.71-2.26) in hard palate, and 2.15 (1.89-2.45) in oropharynx. CONCLUSION: Different anatomic sites had variations in advanced stage of and death from oral cancer and need vigilant surveillance.