Tobacco smoking,chewing habits,alcohol drinking and the risk of head and neck cancer in Nepal

Although tobacco smoking, pan chewing and alcohol drinking are important risk factors for head and neck cancer (HNC), the HNC risks conferred by products available in Nepal for these habits are unknown. We assessed the associations of tobacco smoking, chewing habits, and alcohol drinking with HNC risk in Nepal. A case–control study was conducted in Nepal with 549 incident HNC cases and 601 controls. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression adjusting for potential confounders. We observed increased HNC risk for tobacco smoking (OR: 1.54; 95% CI: 1.14, 2.06), chewing habits (OR: 2.39; 95% CI: 1.77, 3.23), and alcohol drinking (OR: 1.57; 95% CI: 1.14, 2.18). The population attributable fraction (PAF) was 24.3% for tobacco smoking, 39.9% for chewing habits and 23.0% for alcohol drinking. Tobacco smoking, chewing habits, and alcohol drinking might be responsible for 85.3% of HNC cases. Individuals who smoked tobacco, chewed products and drank alcohol had a 13-fold increase in HNC risk (OR: 12.83; 95% CI: 6.91, 23.81) compared to individuals who did not have any of these habits. Both high frequency and long duration of these habits were strong risk factors for HNC among the Nepalese with clear dose–response trends. Preventive strategies against starting these habits and support for quitting these habits are necessary to decrease the incidence of HNC in Nepal.     

Higher carbohydrate intake is associated with increased risk of all‐cause and disease‐specific mortality in head and neck cancer patients: results from a prospective cohort study

No studies have evaluated associations between carbohydrate intake and head and neck squamous cell carcinoma (HNSCC) prognosis. We prospectively examined associations between pre‐ and post‐treatment carbohydrate intake and recurrence, all‐cause mortality, and HNSCC‐specific mortality in a cohort of 414 newly diagnosed HNSCC patients. All participants completed pre‐ and post‐treatment Food Frequency Questionnaires (FFQs) and epidemiologic surveys. Recurrence and mortality events were collected annually. Multivariable Cox Proportional Hazards models tested associations between carbohydrate intake (categorized into low, medium and high intake) and time to recurrence and mortality, adjusting for relevant covariates. During the study period, there were 70 deaths and 72 recurrences. In pretreatment analyses, high intakes of total carbohydrate (HR: 2.29; 95% CI: 1.23–4.25), total sugar (HR: 3.03; 95% CI: 1.12–3.68), glycemic load (HR: 2.10; 95% CI: 1.15–3.83) and simple carbohydrates (HR 2.26; 95% CI 1.19–4.32) were associated with significantly increased risk of all‐cause mortality compared to low intake. High intakes of carbohydrate (HR 2.45; 95% CI: 1.23–4.25) and total sugar (HR 3.03; 95% CI 1.12–3.68) were associated with increased risk of HNSCC‐specific mortality. In post‐treatment analyses, medium fat intake was significantly associated with reduced risk of recurrence (HR 0.08; 95% CI 0.01–0.69) and all‐cause mortality (HR 0.27; 95% CI 0.07–0.96). Stratification by tumor site and cancer stage in pretreatment analyses suggested effect modification by these factors. Our data suggest high pretreatment carbohydrate intake may be associated with adverse prognosis in HNSCC patients. Clinical intervention trials to further examine this hypothesis are warranted.     

Trends in head and neck cancer incidence in relation to smoking prevalence

The trends in head and neck cancer incidence and smoking prevalence are reviewed, discussing where such trends parallel but also how and why they may not. In the U.S., public health efforts at tobacco control and education have successfully reduced the prevalence of cigarette smoking, resulting in a lower incidence of head and neck cancer. Vigilance at preventing tobacco use and encouraging cessation should continue, and expanded efforts should target particular ethnic and socioeconomic groups. However, an unfortunate stagnation has been observed in oropharyngeal cancer incidence and likely reflects a rising attribution of this disease to oncogenic human papillomavirus, in particular type 16 (HPV-16). For the foreseeable future, this trend in oropharyngeal cancer incidence may continue, but with time the effects of vaccination of the adolescent and young adult female population should result in a lower viral prevalence and hopefully a reduced incidence of oropharyngeal cancer. To hasten the reduction of HPV-16 prevalence in the population, widespread vaccination of adolescent and young adult males should also be considered.     

Incidence trends of human papillomavirus‐related head and neck cancer in Taiwan, 1995–2009

Recent studies suggested that human papillomavirus (HPV) is an emerging risk factor of head and neck cancer (HNC), particularly for oropharyngeal cancer. Studies from the West showed a rising trend of HPV‐related HNC despite a decrease of the overall HNC incidence. In contrast, the overall HNC incidence in Taiwan has continued to rise. It is not clear whether the incidence trends of HPV‐related HNC in Taiwan have a similar pattern to those from countries with an overall decreasing incidence of HNC. This study examined the incidence trends of HPV‐related and HPV‐unrelated HNC in Taiwan using data from the Taiwan Cancer Registry. Our results showed that the incidence trends of HPV‐related and HPV‐unrelated HNC in Taiwan both rose during 1995–2009. The incidence of HPV‐related HNC (1.3 per 100,000 in 1995 to 3.3 in 2009, annual percentage change (APC) = 6.9, p < 0.0001) rose more rapidly than the incidence of HPV‐unrelated HNC (10.4 per 100,000 in 1995 to 21.7 in 2009, APC = 5.0, p < 0.0001). The rising trend of HPV‐related HNC was particularly prominent for HNC occurring in tonsil (APC = 8.2, p < 0.0001), in men (APC = 7.5, p < 0.0001), and in those aged between 40 and 50 years (APC = 8.5, p < 0.0001). Although the overall incidence of HNC in Taiwan has continued to increase, the most rapid rise is in the HPV‐related HNC. This suggests that similar to the Western world, HPV‐related HNC is becoming an important public health issue in Taiwan.     

Alcohol and head and neck cancer risk in a prospective study

We investigated the relation between head and neck cancer risk and alcohol consumption in the NIH-AARP Diet and Health Study. During 2,203,500 person-years of follow-up, 611 men and 183 women developed head and neck cancer. With moderate drinking (up to one alcoholic drink per day) as the referent group, non-drinkers showed an increased risk of head and neck cancer (men: hazard ratio (HR) 1.68, 95% confidence interval (95% CI) 1.37-2.06; women: 1.46, 1.02-2.08). Among male and female alcohol drinkers, we observed a significant dose-response relationship between alcohol consumption and risk. The HR for consuming >3 drinks per day was significantly higher in women (2.52, 1.46-4.35) than in men (1.48, 1.15-1.90; P for interaction=0.0036). The incidence rates per 100 000 person-years for those who consumed >3 drinks per day were similar in men (77.6) and women (75.3). The higher HRs observed in women resulted from lower incidence rates in the referent group: women (14.7), men (34.4). In summary, drinking >3 alcoholic beverages per day was associated with increased risk in men and women, but consumption of up to one drink per day may be associated with reduced risk relative to non-drinking.     

Associations of cigarette smoking and alcohol drinking with stomach cancer survival: A prospective patient cohort study in Japan

Cigarette smoking and alcohol drinking may affect the prognosis of stomach cancer, but evidence has been inconsistent. We investigated the associations between pretreatment smoking and alcohol drinking and the risk of all‐cause and stomach cancer death among 1,576 patients with histologically confirmed stomach cancer diagnosed during 1997–2010 at a single hospital in Japan. Histories of smoking and alcohol drinking were assessed using a self‐administered questionnaire. The patients were followed until December 31, 2013. The Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During 9,625.1 person‐years, 670 all‐cause and 419 stomach cancer deaths were documented. Among the patients overall, ever‐drinking was significantly associated with an increased risk of all‐cause death (HR: 1.25; 95% CI: 1.03–1.51), but not stomach cancer death. Positive linear associations with the frequency of drinking (p_trend = 0.02) and the amount of alcohol consumed per day (p_trend = 0.03) were observed for the risk of all‐cause death. Ever‐smoking was not related to either the risk of all‐cause or stomach cancer death. Conversely, among the patients who underwent curative resection, a significant positive association was found between ever‐smoking and the risk of stomach cancer death (HR: 2.44; 95% CI: 1.17–5.08). A positive association was also found for earlier age at start of smoking (p_trend = 0.0046). Pretreatment smoking and alcohol drinking have significant effects on stomach cancer survival. Lifestyle adjustments throughout life may improve survival.     

Epigenetic inactivation of the SFRP genes is associated with drinking, smoking and HPV in head and neck squamous cell carcinoma

The soluble frizzled receptor protein (SFRP) family encodes antagonists of the WNT pathway, and silencing of these genes, through promoter hypermethylation, leads to constitutive WNT signaling. In bladder cancers, hypermethylation of the SFRP genes occurs more often in current and former smokers and is a strong predictor of poor patient survival. Hence, we examined methylation of these genes in another tobacco-related epithelial cancer, head and neck squamous cell carcinoma (HNSCC), to determine if the pattern of tobacco exposure again predicts the epigenetic alteration of these genes. Using methylation-specific PCR, the prevalence of methylation of SFRP1, SFRP2, SFRP4 and SFRP5 was 35, 32, 35 and 29%, respectively among 350 HNSCC cases. Promoter methylation of SFRP1 occurred more often in both heavy (OR 3.5, 95% CI 0.9-13.7) and light drinkers (OR 3.7, 95% CI 1.0-14.3) compared to nondrinkers. SFRP4 promoter methylation, on the other hand, occurred at a higher prevalence in never smokers and former smokers than in current smokers, and also was independently associated with HPV16 viral DNA. A joint effects model of SFRP4 promoter methylation demonstrated that smoking status and HPV virus significantly interacted (p < 0.04) such that never smokers with HPV16 had an OR of SFRP4 methylation of 9.0 (95% CI 2.1-38.6). These results suggest that epigenetic alterations of the SFRP genes are highly prevalent in HNSCC, and that the clonal selection for these alterations is complex and may be related to the carcinogenic exposures that are known risk factors for this disease.     

Characteristics and survival of head and neck cancer by HPV status: a cancer registry-based study

Elucidation of the role of human papillomavirus (HPV) in the etiology and prognosis of squamous carcinomas of the head and neck (HNSCC) is essential to optimize prevention and treatment strategies for this disease. We analyzed 385 HNSCC tissue blocks identified through a population-based cancer registry in Metropolitan Detroit for HPV DNA using a broad-spectrum PCR technique (SPF10-LiPA25) to correlate with patient and tumor characteristics and overall survival. Overall, HPV DNA (any type) was detected in 29.4% of all HNSCC, but it was significantly more prevalent (50.6%) in oropharyngeal sites (N=81), where 90% of HPV were type 16, than in other sites. HPV prevalence (any type) in oropharyngeal sites was highest in patients with a negative smoking indicator, Caucasians and in regional tumor stage. Likewise, only in oropharyngeal sites did patients overall positive to HPV show significantly better survival compared with HPV-negative patients, notably among those who had been irradiated. The best and the worst survival from cancer in oropharyngeal sites were found, respectively, among HPV-positive patients with negative smoking indicator and among HPV-negative patients with positive smoking indicator. The results of this study revealed that the presence of HPV DNA was associated with patients' specific characteristics and better overall survival exclusively in oropharyngeal sites. To define the fraction of HNSCC preventable by HPV vaccination or amenable to less aggressive treatment, however, tobacco exposure and HPV markers other than DNA presence need to be taken into account.     

Cigarette smoking, alcohol drinking and the risk of gallbladder cancer death: a prospective cohort study in Japan

Gallbladder cancer is a rare cancer with a poor prognosis, and few risk factors have been identified to date. This prospective study was conducted to evaluate the association of cigarette smoking and alcohol consumption with the risk of gallbladder cancer death. A baseline survey in 45 areas throughout Japan was conducted from 1988 to 1990 using a self-administered questionnaire, and a total of 113,496 participants (65,740 women) aged 40-89 years at entry were followed for 15 years. During the follow-up period, 165 gallbladder cancer deaths (95 women) were observed. Among women, the hazard ratio (HR) [95 percent confidence interval: 95% CI] of current smoker was 2.00 [0.91-4.42], when adjusted for age and drinking. There was no clear association between alcohol consumption and the risk. Among men, HR of current smoker was 2.27 [1.05-4.90]. HRs of those who smoked 21 cigarettes or more per day and those with 801-1,000 cigarette-years were 3.18 [1.18-8.53] and 3.44 [1.40-8.45], respectively, and positive linear associations were observed between that risk and the number of cigarettes per day (p for trend = 0.007) or "cigarette-years" (p for trend = 0.012). The alcohol dose was linearly associated with risk (p for trend = 0.004), where the HR among those who consumed 72.0 g or more of alcohol per day was 3.60 [1.29-9.85]. Among both men and women, cigarette smoking may elevate the risk of death from gallbladder cancer. Drinking may pose an elevated risk among men, but that seems to be less true among women.     

Predictors of smoking relapse in patients with thoracic cancer or head and neck cancer

BACKGROUND:

Cancer patients who continue smoking are at increased risk for adverse outcomes including reduced treatment efficacy and poorer survival rates. Many patients spontaneously quit smoking after diagnosis; however, relapse is understudied. The goal of this study was to evaluate smoking‐related, affective, cognitive, and physical variables as predictors of smoking after surgical treatment among patients with lung cancer and head and neck cancer.

METHODS:

A longitudinal study was conducted with 154 patients (57% male) who recently quit smoking. Predictor variables were measured at baseline (ie, time of surgery); smoking behavior was assessed at 2, 4, 6, and 12 months after surgery. Analyses of 7‐day point prevalence were performed using a Generalized Estimating Equations approach.

RESULTS:

Relapse rates varied significantly depending on presurgery smoking status. At 12 months after surgery, 60% of patients who smoked during the week prior to surgery had resumed smoking versus only 13% who were abstinent prior to surgery. Smoking rates among both groups were relatively stable across the 4 follow‐ups. For patients smoking before surgery (N = 101), predictors of smoking relapse included lower quitting self‐efficacy, higher depression proneness, and greater fears about cancer recurrence. For patients abstinent before surgery (N = 53), higher perceived difficulty quitting and lower cancer‐related risk perceptions predicted smoking relapse.

CONCLUSIONS:

Efforts to encourage early cessation at diagnosis, and increased smoking relapse‐prevention efforts in the acute period following surgery, may promote long‐term abstinence. Several modifiable variables are identified to target in future smoking relapse‐prevention interventions for cancer patients. Cancer 2013. © 2012 American Cancer Society.     

Human papillomavirus in head and neck cancer: Molecular biology and clinicopathological correlations

Human papillomaviruses are known to cause cancers of the cervix and other anogenital tract sites. Epidemiologic and molecular pathology studies have also suggested that HPV infection may be associated with cancers of the head and neck. Modes of transmission of HPV infection in the head and neck region have not been fully resolved; however, perinatal transmission and an association between sexual behavior and risk for HPV-positive cancers have been presented.Among the HPV types infecting the mucosa, high-risk, intermediate-risk and low-risk genotypes are defined, depending on their presence in carcinoma or precursor lesions. The phylogenic groups of HPVs also showed a definite correlation with the morphology of head and neck tumors. The groups A6, A7, and A9 include viruses that are frequently demonstrated in basaloid and verrucosus squamous cell carcinomas known to associate with HPV infection. Integration of HPV DNA into the host cell genome occurs early in cancer development and is an important event in malignant transformation.There is a trend for patients with HPV-positive tumors to be nondrinkers or light drinkers, the majority of these patients are females, and the median age is lower than in the case of HPV-negative tumors, but this latter difference was not always statistically significant. In the Kaplan-Meier survival model, the HPV-positive verrucous and basaloid squamous cell carcinomas showed better survival rates than the HPV-negative typical squamous cell carcinomas. An increased radiocurability of HPV-positive head and neck squamous cell carcinoma (HNSCC) has also been demonstrated.     

Platinum-based regimens versus cetuximab in definitive chemoradiation for human papillomavirus-unrelated head and neck cancer

For patients ineligible for cisplatin with definitive radiotherapy (CP-CRT) for locally advanced head and neck squamous cell carcinoma (LA-HNSCC), concurrent cetuximab (C225-RT) is a popular substitute. Carboplatin-based chemoradiation (CB-CRT) is another option; however, relative efficacies of CP-CRT, CB-CRT and C225-RT are unclear, particularly in the human papillomavirus (HPV)-unrelated population. We identified 316 patients with stage III-IVB cancers of the oropharynx (24.7%), larynx (58.2%) and hypopharynx (17.1%) undergoing definitive C225-RT (N = 61), CB-CRT (N = 74) or CP-CRT (N = 181). Kaplan-Meier and cumulative incidence functions were generated to estimate overall survival (OS), locoregional failure (LRF) and distant metastasis (DM). Cox proportional hazards were used to determine the association of survival endpoints with clinical characteristics. Respectively, 3-year cumulative incidences for CP-CRT, CB-CRT and C225-RT were: LRF (0.19, 0.18 and 0.48, p ≤ 0.001), DM (0.17, 0.12 and 0.25, p = 0.32). Kaplan-Meier estimates for 3 year OS were: CP-CRT: 71%; CB-CRT: 59% and C225-RT: 54%; p = 0.0094. CP-CRT (hazard ratio [HR] 0.336; 95% confidence interval [CI] 0.203–0.557, p < 0.01) and CB-CRT (HR 0.279; 95% CI 0.141–0.551, p < 0.01) were associated with reduced hazard for LRF on multivariable analysis. CP-CRT (HR 0.548; 95% CI 0.355–0.845, p < 0.01) and CB-CRT (HR 0.549; 95% CI 0.334–0.904, p = 0.02) were associated with a reduced hazard for death on multivariable analysis. Propensity matching confirmed reduced hazards with a combined CP/CB-CRT group compared to C225-RT for LRF: HR 0.384 (p = 0.018) and OS: HR 0.557 (p = 0.045) and CB-CRT group compared to C225-RT for LRF: HR 0.427 (p = 0.023). In conclusion, CB-CRT is an effective alternative to CP-CRT in HPV-unrelated LA-HNSCC with superior locoregional control and OS compared to C225-RT.     

Human papillomavirus status in head and neck cancer

Human papillomavirus (HPV) is an emerging causative factor for squamous carcinoma of the oropharynx and perhaps other head and neck cancers. There is a great deal of uncertainty regarding the clinical significance and implications of HPV status in this patient population. As a result, there is no established protocol for informing patients of the potential link between viral infection and their cancer. This paper discusses some of the ethical issues involved with informing head and neck cancer patients of their HPV status, recognizing the dilemma posed by unresolved clinical questions and the need to respect the autonomy of patients by disclosing relevant information. Cancer 2010; 116:4221–6. © 2010 American Cancer Society.     

Proinflammatory diet is associated with increased risk of squamous cell head and neck cancer

Diets high in fruits and vegetables and low in red meat intake have been associated with decreased risk of head and neck cancer. Additionally, chronic inflammation pathways and their association with cancer have been widely described. We hypothesized a proinflammatory diet, as measured by the dietary inflammatory index (DII^®), is associated with increased risk of head and neck cancer. We used the Carolina Head and Neck Cancer (CHANCE) study, a population‐based case–control study of head and neck squamous cell carcinoma. Cases were recruited from a 46‐county region in central North Carolina. Controls, frequency‐matched on age, race, and sex were identified through the North Carolina Department of Motor Vehicle records. The DII score, adjusted for energy using the density approach (E‐DII), was calculated from a food frequency questionnaire and split into four quartiles based on the distribution among controls. Adjusted odds ratios (ORs) were estimated with unconditional logistic regression. Cases had higher E‐DII scores (i.e., a more proinflammatory diet) compared with controls (mean: ?0.14 vs. ?1.50; p value < 0.001). When compared with the lowest quartile, the OR for the highest quartile was 2.91 (95% confidence interval (CI): 2.16–3.95), followed by 1.93 (95% CI: 1.43–2.62) for the third quartile, and 1.37 (95% CI: 1.00–1.89) for the second quartile. Both alcohol and smoking had a significant additive interaction with E‐DII (smoking relative excess risk due to interaction (RERI): 2.83; 95% CI: 1.36–4.30 and alcohol RERI: 1.75; 95% CI: 0.77–2.75). These results provide additional evidence for the association between proinflammatory diet and head and neck cancer.