Prognostic factors for esophageal squamous cell Carcinoma-A Population-Based study in Golestan province, Iran, a high incidence area

Golestan Province in northern Iran is an area with a high incidence of esophageal squamous cell carcinoma (ESCC). We aimed to investigate prognostic factors for ESCC and survival of cases in Golestan, on which little data were available. We followed-up 426 ESCC cases participating in a population-based case-control study. Data were analyzed using the Kaplan-Meier method and the Cox proportional hazard models. Median survival was 7 months. Age at diagnosis was inversely associated with survival, but the association was disappeared with adjustment for treatment. Residing in urban areas (hazard ratio, HR = 0.70; 95 CI 0.54-0.90) and being of non-Turkmen ethnic groups (HR = 0.76; 95 CI 0.61-0.96) were associated with better prognosis. In contrast to other types of tobacco use, nass (a smokeless tobacco product) chewing was associated with a slightly poorer prognosis even in models adjusted for other factors including stage of disease and treatment (HR = 1.38; 95 CI 0.99-1.92). Opium use was associated with poorer prognosis in crude analyses but not in adjusted models. Almost all of potentially curative treatments were associated with longer survival. Prognosis of ESCC in Golestan is very poor. Easier access to treatment facilities may improve the prognosis of ESCC in Golestan. The observed association between nass chewing and poorer prognosis needs further investigations; this association may suggest a possible role for ingestion of nass constituents in prognosis of ESCC. © 2011 Aghcheli et al

The association between diet quality and cancer incidence of the head and neck

The association between diet quality and head and neck cancer (HNC) was explored using a population-based case–control study of 1170 HNC cases and 1303 age-, race-, and sex-matched controls from the United States. Diet quality was assessed with three diet quality scores (DQS): (a) Healthy Eating Index 2005 (HEI-2005), (b) Mediterranean Diet Score (MDS), and (c) HNC-specific Mediterranean Diet Score (MDS-HNC), a modified MDS that we developed to be more applicable to HNC. Logistic regression models estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) representing diet quality–incident HNC associations. We examined effect measure modification (EMM) by body mass index (BMI), race, cigarette smoking, and alcohol consumption and associational heterogeneity by HPV-positivity and tumor site. A one standard deviation summary DQS decrement suggested a consistent inverse association (ORs (CIs)) for the HEI-2005, MDS, and MDS-HNC: 1.35 (1.21, 1.50), 1.13 (1.02, 1.25), and 1.17 (1.06, 1.31), respectively. This association did not vary by tumor site or tumor HPV status, though additive EMM by alcohol use and by BMI was observed. Our findings suggest the Mediterranean diet can be used to study HNC in American populations, and that poor diet quality elevates HNC incidence, particularly among alcohol users

Association of tooth loss and oral hygiene with risk of gastric adenocarcinoma

Poor oral health and tooth loss have been proposed as possible risk factors for some chronic diseases, including gastric cancer. However, a small number of studies have tested these associations. We conducted a case-control study in Golestan Province, Iran, that enrolled 309 cases diagnosed with gastric adenocarcinoma (118 noncardia, 161 cardia, and 30 mixed-locations) and 613 sex, age, and neighborhood matched controls. Data on oral health were obtained through physical examination and questionnaire including tooth loss, the number of decayed, missing, and filled teeth, and frequency of tooth brushing. ORs and 95% confidence intervals (95% CI) were obtained using conditional logistic regression models adjusted for potential confounders. Standard one degree-of-freedom linear trend test and a multiple degree-of-freedom global test of the effect of adding oral hygiene variables to the model were also calculated. Our results showed apparent associations between tooth loss and decayed, missing, filled teeth (DMFT) score with risk of gastric cancer, overall and at each anatomic subsite. However, these associations were not monotonic and were strongly confounded by age. The results also showed that subjects who brushed their teeth less than daily were at significantly higher risk for gastric cardia adenocarcinoma ORs (95% CI) of 5.6 (1.6-19.3). We found evidence for an association between oral health and gastric cancer, but the nonmonotonic association, the relatively strong effect of confounder adjustment, and inconsistent results across studies must temper the strength of any conclusions. © 2013 AACR

Oral health and human papillomavirus-associated head and neck squamous cell carcinoma

BACKGROUND: Indicators of poor oral health, including smoking, have been associated with increased risk of head and neck squamous cell carcinoma, especially oropharyngeal squamous cell carcinoma (OPSCC), yet few studies have examined whether this association is modified by human papillomavirus (HPV) status. METHODS: Data from interviews and tumor HPV status from a large population-based case-control study, the Carolina Head and Neck Cancer Study (CHANCE), were used to estimate the association between oral health indicators and smoking among 102 HPV-positive patients and 145 HPV-negative patients with OPSCC and 1396 controls. HPV status was determined by p16INK4a (p16) immunohistochemistry. Unconditional, multinomial logistic regression was used to estimate odds ratios (ORs) for all oral health indictors adjusting for important covariates. RESULTS: Routine dental examinations were associated with a decreased risk of both HPV-negative OPSCC (OR, 0.52; 95% confidence interval [CI], 0.35-0.76) and HPV-positive OPSCC (OR, 0.55; 95% CI, 0.36-.86). Tooth mobility (a proxy for periodontal disease) increased the risk of HPV-negative disease (OR, 1.70; 95% CI, 1.18-2.43) slightly more than the risk for HPV-positive disease (OR, 1.45; 95% CI, 0.95-2.20). Ten or more pack-years of cigarette smoking were strongly associated with an increased risk of HPV-negative OPSCC (OR, 4.26; 95% CI, 2.85-6.37) and were associated less with an increased risk of HPV-positive OPSCC (OR, 1.62; 95% CI, 1.10-2.38). CONCLUSIONS: Although HPV-positive and HPV-negative HNSCC differ significantly with respect to etiology and tumorigenesis, the current findings suggest a similar pattern of association between poor oral health, frequency of dental examinations, and both HPV-positive and HPV-negative OPSCC. Future research is required to elucidate interactions between poor oral health, tobacco use, and HPV in the development of OPSCC. Cancer 2017;71–80. © 2016 American Cancer Society

Evaluation of pathologic staging using number of nodes in p16-negative head and neck cancer

Objectives: The 8th edition AJCC staging guidelines for head and neck squamous cell carcinoma (HNSCC) recently introduced pathologic staging criteria for nodal disease among p16-positive patients. In this study we evaluate pathologic staging in p16-negative HNSCC. Materials and Methods: We compared pathologic staging to the 7th and 8th edition AJCC staging systems using a statewide population-based cohort. All M0 p16-negative surgical patients were included. The outcome was five-year overall survival. Results: Of 304 patients identified, 113 were N0, 157 had 1–4 positive nodes, and 34 had ≥4 nodes. Survival was 71% (95% CI 61–78%) with no nodes, 48% (36%−60%) for 1–4 nodes, and 24% (11 – 39%) for > 4 nodes. When compared to the AJCC systems, the pathologic staging yielded a larger total survival gradient, more montonic survival, better consistency across primary sites, and a slightly lower Bayesian information criterion (1510 vs 1538). After adjusting for disease characteristics, demographics, and tobacco use, hazard ratios for survival were similar using pathologic and AJCC criteria. Conclusion: In this cohort, pathological staging was more prognostic than AJCC staging. This is the first study to evaluate pathologic staging in p16-negative cancer; if these findings are verified, a universal nodal staging system could be introduced

Socioeconomic status, access to care, risk factor patterns, and stage at diagnosis for head and neck cancer among black and white patients

Background: Little is known about how factors combine to influence progression of squamous cell carcinoma of the head and neck (HNSCC). We aimed to evaluate multidimensional influences of factors associated with HNSCC stage by race. Methods: Using retrospective data, patients with similar socioeconomic status (SES), access to care (travel time/distance), and behavioral risk factors (tobacco/alcohol use and dental care) were grouped by latent class analysis. Relative frequency differences (RFD) were calculated to evaluate latent classes by stage, race, and p16 status. Results: We identified three latent classes. Advanced T-stage was higher for black (RFD = +20.2%; 95% CI: −4.6 to 44.9) than white patients (RFD = +10.7%; 95% CI: 2.1–19.3) in the low-SES/high-access/high-behavioral risk class and higher for both black (RFD = +29.6%; 95% CI: 4.7–54.5) and white patients (RFD = +23.9%; 95% CI: 15.2–32.6) in the low-SES/low-access/high-behavioral risk class. Conclusion: Results suggest that SES, access to care, and behavioral risk factors combine to underly the association with advanced T-stage. Additionally, differences by race warrant further investigation

A common classification framework for neuroendocrine neoplasms: an International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal

The classification of neuroendocrine neoplasms (NENs) differs between organ systems and currently causes considerable confusion. A uniform classification framework for NENs at any anatomical location may reduce inconsistencies and contradictions among the various systems currently in use. The classification suggested here is intended to allow pathologists and clinicians to manage their patients with NENs consistently, while acknowledging organ-specific differences in classification criteria, tumor biology, and prognostic factors. The classification suggested is based on a consensus conference held at the International Agency for Research on Cancer (IARC) in November 2017 and subsequent discussion with additional experts. The key feature of the new classification is a distinction between differentiated neuroendocrine tumors (NETs), also designated carcinoid tumors in some systems, and poorly differentiated NECs, as they both share common expression of neuroendocrine markers. This dichotomous morphological subdivision into NETs and NECs is supported by genetic evidence at specific anatomic sites as well as clinical, epidemiologic, histologic, and prognostic differences. In many organ systems, NETs are graded as G1, G2, or G3 based on mitotic count and/or Ki-67 labeling index, and/or the presence of necrosis; NECs are considered high grade by definition. We believe this conceptual approach can form the basis for the next generation of NEN classifications and will allow more consistent taxonomy to understand how neoplasms from different organ systems inter-relate clinically and genetically

Predictors of oropharyngeal cancer survival in Europe

Objectives: HPV16-positive oropharyngeal cancer (OPC) patients experience better outcomes compared to HPV16-negative patients. Currently, strategies for treatment de-escalation are based on HPV status, smoking history and disease stage. However, the appropriate cut-point for smoking and the role of other non-clinical factors in OPC survival remains uncertain. Materials and Methods: We examined factors associated with OPC outcome in 321 patients recruited in a large European multi-center study. Seropositivity for HPV16 E6 was used as a marker of HPV16 positive cancer. Hazard ratios (HR) and confidence intervals (CI) were estimated using Cox proportional models adjusted for potential confounders. Results: Overall 5-year survival following OPC diagnosis was 50%. HPV16-positive OPC cases were at significantly lower risk of death (aHR = 0.51, 95% CI: 0.32–0.80). A significant effect on OPC survival was apparent for female sex (aHR 0.50: 95% CI: 0.29–0.85) and being underweight at diagnosis (aHR: 2.41, 95% CI: 1.38–4.21). A 10 pack year smoking history was not associated with overall survival. Higher stage at diagnosis appeared as the only factor significantly associated with OPC recurrence (aHR: 4.88, 95% CI: 2.12–11.21). Conclusion: This study confirms that HPV16 status is an independent prognostic factor for OPC survival while female sex lowers risk of death and being underweight at diagnosis increases the risk of death. Smoking was not an independent predictor of OPC survival.</p

Extremely High Tp53 Mutation Load in Esophageal Squamous Cell Carcinoma in Golestan Province, Iran

Background: Golestan Province in northeastern Iran has one of the highest incidences of esophageal squamous cell carcinoma (ESCC) in the world with rates over 50 per 100,000 person-years in both sexes. We have analyzed TP53 mutation patterns in tumors from this high-risk geographic area in search of clues to the mutagenic processes involved in causing ESCC. Methodology/Principal Findings: Biopsies of 119 confirmed ESCC tumor tissue from subjects enrolled in a case-control study conducted in Golestan Province were analyzed by direct sequencing of TP53 exons 2 through 11. Immunohistochemical staining for p53 was carried out using two monoclonal antibodies, DO7 and 1801. A total of 120 TP53 mutations were detected in 107/119 cases (89.9), including 11 patients with double or triple mutations. The mutation pattern was heterogeneous with infrequent mutations at common TP53 "hotspots" but frequent transversions potentially attributable to environmental carcinogens forming bulky DNA adducts, including 40 at bases known as site of mutagenesis by polycyclic aromatic hydrocarbons (PAHs). Mutations showed different patterns according to the reported temperature of tea consumption, but no variation was observed in relation to ethnicity, tobacco or opium use, and alcoholic beverage consumption or urban versus rural residence. Conclusion/Significance: ESCC tumors in people from Golestan Province show the highest rate of TP53 mutations ever reported in any cancer anywhere. The heterogeneous mutation pattern is highly suggestive of a causative role for multiple environmental carcinogens, including PAHs. The temperature and composition of tea may also influence mutagenesis

Breast cancer survival and survival gap apportionment in sub-Saharan Africa (ABC-DO): a prospective cohort study

Background: Breast cancer is the second leading cause of death from cancer in women in sub-Saharan Africa, yet there are few well characterised large-scale survival studies with complete follow-up data. We aimed to provide robust survival estimates in women in this setting and apportion the survival gaps. Methods: The African Breast Cancer-Disparities in Outcomes (ABC-DO) prospective cohort study was done at eight hospitals across five sub-Saharan African countries (Namibia, Nigeria, South Africa, Uganda, and Zambia). We prospectively recruited women (aged ≥18 years) who attended these hospitals with suspected breast cancer. Women were actively followed up by use of a telephone call once every 3 months, and a mobile health application was used to keep a dynamic record of follow-up calls due. We collected detailed sociodemographic, clinical, and treatment data. The primary outcome was 3-year overall survival, analysed by use of flexible proportional mortality models, and we predicted survival under scenarios of modified distributions of risk factors. Findings: Between Sept 8, 2014, and Dec 31, 2017, 2313 women were recruited from these eight hospitals, of whom 85 did not have breast cancer. Of the remaining 2228 women with breast cancer, 58 women with previous treatment or recurrence, and 14 women from small racial groups (white and Asian women in South Africa), were excluded. Of the 2156 women analysed, 1840 (85%) were histologically confirmed, 129 (6%) were cytologically confirmed, and 187 (9%) were clinically confirmed to have breast cancer. 2156 (97%) women were followed up for up to 3 years or up to Jan 1, 2019, whichever was earlier. Up to this date, 879 (41%) of these women had died, 1118 (52%) were alive, and 159 (7%) were censored early. 3-year overall survival was 50% (95% CI 48–53), but we observed variations in 3-year survival between different races in Namibia (from 90% in white women to 56% in Black women) and in South Africa (from 76% in mixed-race women to 59% in Black women), and between different countries (44–47% in Uganda and Zambia vs 36% in Nigeria). 215 (10%) of all women had died within 6 months of diagnosis, but 3-year overall survival remained low in women who survived to this timepoint (58%). Among survival determinants, improvements in early diagnosis and treatment were predicted to contribute to the largest increases in survival, with a combined absolute increase in survival of up to 22% in Nigeria, Zambia, and Uganda, when compared with the contributions of other factors (such as HIV or aggressive subtypes). Interpretation: Large variations in breast cancer survival in sub-Saharan African countries indicate that improvements are possible. At least a third of the projected 416 000 breast cancer deaths that will occur in this region in the next decade could be prevented through achievable downstaging and improvements in treatment. Improving survival in socially disadvantaged women warrants special attention. Funding: Susan G Komen and the International Agency for Research on Cancer