Elaine M. Smith

Interaction between tobacco and alcohol use and the risk of head and neck cancer: Pooled analysis in the international head and neck cancer Epidemiology consortium

Background: The magnitude of risk conferred by the interaction between tobacco and alcohol use on the risk of head and neck cancers is not clear because studies have used various methods to quantify the excess head and neck cancer burden. Methods: We analyzed individual-level pooled data from 17 European and American case-control studies (11,221 cases and 16,168 controls) participating in the International Head and Neck Cancer Epidemiology consortium. We estimated the multiplicative interaction parameter (ψ) and population attributable risks (PAR). Results: A greater than multiplicative joint effect between ever tobacco and alcohol use was observed for head and neck cancer risk (ψ = 2.15; 95% confidence interval, 1.53-3.04). The PAR for tobacco or alcohol was 72% (95% confidence interval, 61-79%) for head and neck cancer, of which 4% was due to alcohol alone, 33% was due to tobacco alone, and 35% was due to tobacco and alcohol combined. The total PAR differed by subsite (64% for oral cavity cancer, 72% for pharyngeal cancer, 89% for laryngeal cancer), by sex (74% for men, 57% for women), by age (33% for cases <45 years, 73% for cases >60 years), and by region (84% in Europe, 51% in North America, 83% in Latin America). Conclusions: Our results confirm that the joint effect between tobacco and alcohol use is greater than multiplicative on head and neck cancer risk. However, a substantial proportion of head and neck cancers cannot be attributed to tobacco or alcohol use, particularly for oral cavity cancer and for head and neck cancer among women and among young-onset cases. (Cancer Epidemiol Biomarkers Prev 2009;18(2):541–50)

Age, sexual behavior and human papillomavirus infection in oral cavity and oropharyngeal cancers.

There are few well‐established patient risk factors associated with human papillomavirus (HPV) infection in cancers of the oral cavity and oropharynx. The purpose of this study was to determine if there were significant different risk factors and tumor characteristics between HPV‐positive and HPV‐negative cancer cases. HPV was evaluated in cancer tissue and exfoliated oral cells of 193 oral cavity/oropharynx cancer patients using PCR and direct DNA sequencing. A patient questionnaire collected information about risk factors, sexual practices and medical history. The prevalence of HPV high‐risk (HR) types was 20% in cancer cases. Three types were identified: HPV‐16 (87%), HPV‐18 (3%) and HPV‐33 (11%). Risk factors for HPV‐HR included younger age (≤ 55 years vs. > 55 years; adjusted OR = 3.4; 95% CI = 1.6–7.3) and younger‐age cases who had more lifetime sex partners (adjusted OR = 3.8; 95% CI = 1.4–10.1), practiced oral‐genital sex (adjusted OR = 4.3; 95% CI = 1.8–10.4) or oral‐anal sex (adjusted OR = 19.5; 95% CI = 3.4–113). Compared to HPV‐negative cancers, HPV‐HR cancers were more likely to have a positive HPV‐HR exfoliated oral cytology test (adjusted OR = 7.8; 95% CI = 3.4–18.4), later stage (adjusted OR = 3.0), nodal involvement (adjusted OR = 4.1) and advanced grade (adjusted OR = 3.0). This study shows new evidence that the prevalence of oncogenic mucosal HPV is higher in younger‐age oral cavity/oropharynx cancer cases whose sexual practices are typically associated with sexual transmission of the virus. HPV detection also appears to be an indicator of advanced disease characteristics that may require different clinical treatment for this subset of patients. An exfoliated oral cytology test for HPV was a significant predictor of HR types in the cancers, suggesting that an oral rinse may provide an early biomarker of infected tumors.

Human papillomavirus infection as a prognostic factor in carcinomas of the oral cavity and oropharynx

Although studies have established human papillomaviruses (HPVs) as a risk factor for oral and oropharyngeal cancer, it is not clear whether viral infection affects survival in head and neck malignancies. This investigation examined the relationship between HPV and survival in carcinomas of the oral cavity and oropharynx. Formalin‐fixed, paraffin‐embedded tumor specimens from 139 newly diagnosed cases were tested for HPVs by PCR and DNA sequencing. Patient and tumor characteristics were obtained from questionnaires, pathology reports and cancer registries. Odds ratios (ORs) and relative risks (RRs) were based on logistic and Cox regression models, respectively. HPVs were detected in 21% of the tumors; 83% were HPV‐16. Greater risk of HPV infection was associated with males (OR = 2.9, 95% CI = 1.0–8.6), a history of oral‐genital sex (OR = 4.2, 95% CI = 1.5–11.7), and oropharyngeal tumors (OR = 10.4, 95% CI = 3.5–31.2). As tobacco usage increased, the odds of HPV detection decreased (OR = 0.97/pack‐year, 95% CI = 0.96–0.99). HPV infected patients had better overall survival (RR = 0.3, 95% CI = 0.1–0.8) than those with HPV‐negative tumors. There was an interaction between gender and HPV for overall (p = 0.05) and disease‐specific (p = 0.03) survival that suggested that HPV infected males had better prognosis than HPV‐negative males, but this was not the case among females. HPV status was identified as an independent prognostic factor in oral and oropharyngeal cancers. This result appeared to be gender‐specific, suggesting the need for further study of the interaction between HPV and gender on survival.

Voice disorders in the general population : Prevalence, risk factors, and occupational impact

Objectives: Epidemiologic studies of the prevalence and risk factors of voice disorders in the general adult population are rare. The purpose of this investigation was to 1) determine the prevalence of voice disorders, 2) identify variables associated with increased risk of voice disorders, and 3) establish the functional impact of voice disorders on the general population.

Frequency and effects of teachers' voice problems***

This study compared the frequency and effects of voice symptoms in teachers to a group of individuals employed in other occupations. Teachers were more likely to report having a voice problem (15 vs. 6%), having 10 specific voice symptoms, and having 5 symptoms of physical discomfort. They averaged almost 2 symptoms compared with none for nonteachers. Likewise, teachers were more likely to perceive that a voice problem would adversely affect their future career options, had done so in the past, and was limiting their current job performance. Over 20% of teachers but none of the nonteachers had missed any days of work due to a voice problem. These findings suggest that teaching is a high-risk occupation for voice disorders and that this health problem may have significant work-related and economic effects.

Fundamental Differences in Cell Cycle Deregulation in Human Papillomavirus–Positive and Human Papillomavirus–Negative Head/Neck and Cervical Cancers

Human papillomaviruses (HPV) are associated with nearly all cervical cancers, 20% to 30% of head and neck cancers (HNC), and other cancers. Because HNCs also arise in HPV-negative patients, this type of cancer provides unique opportunities to define similarities and differences of HPV-positive versus HPV-negative cancers arising in the same tissue. Here, we describe genome-wide expression profiling of 84 HNCs, cervical cancers, and site-matched normal epithelial samples in which we used laser capture microdissection to enrich samples for tumor-derived versus normal epithelial cells. This analysis revealed that HPV(+) HNCs and cervical cancers differed in their patterns of gene expression yet shared many changes compared with HPV(-) HNCs. Some of these shared changes were predicted, but many others were not. Notably, HPV(+) HNCs and cervical cancers were found to be up-regulated in their expression of a distinct and larger subset of cell cycle genes than that observed in HPV(-) HNC. Moreover, HPV(+) cancers overexpressed testis-specific genes that are normally expressed only in meiotic cells. Many, although not all, of the hallmark differences between HPV(+) HNC and HPV(-) HNC were a direct consequence of HPV and in particular the viral E6 and E7 oncogenes. This included a novel association of HPV oncogenes with testis-specific gene expression. These findings in primary human tumors provide novel biomarkers for early detection of HPV(+) and HPV(-) cancers, and emphasize the potential value of targeting E6 and E7 function, alone or combined with radiation and/or traditional chemotherapy, in the treatment of HPV(+) cancers.

Frequency of voice problems among teachers and other occupations.

This study describes the frequency of reporting vocal problems among a random sample of elementary and high school teachers (n = 554) compared to individuals working in other occupations (n = 220). Teachers were more likely to define themselves as ever having a voice problem (32% versus. 1%, p < .05); having a tired, weak, or effortful voice (p < .05 each); and having a higher frequency of symptoms of physical discomfort with speaking (p < .05). They also were more likely to perceive that their voice problem negatively affected current job performance (p < .05) and limited options regarding change in work (p < .05). About 20% of teachers but only 4% of nonteachers had missed work due to their voice. These findings suggest that teachers are at high-risk for disability from voice disorders and that this health problem may have significant work-related and economic effects.

Sexual behaviours and the risk of head and neck cancers: a pooled analysis in the International Head and Neck Cancer Epidemiology (INHANCE) consortium

BACKGROUND Sexual contact may be the means by which head and neck cancer patients are exposed to human papillomavirus (HPV). METHODS We undertook a pooled analysis of four population-based and four hospital-based case-control studies from the International Head and Neck Cancer Epidemiology (INHANCE) consortium, with participants from Argentina, Australia, Brazil, Canada, Cuba, India, Italy, Spain, Poland, Puerto Rico, Russia and the USA. The study included 5642 head and neck cancer cases and 6069 controls. We calculated odds ratios (ORs) of associations between cancer and specific sexual behaviours, including practice of oral sex, number of lifetime sexual partners and oral sex partners, age at sexual debut, a history of same-sex contact and a history of oral-anal contact. Findings were stratified by sex and disease subsite. RESULTS Cancer of the oropharynx was associated with having a history of six or more lifetime sexual partners [OR = 1.25, 95% confidence interval (CI) 1.01, 1.54] and four or more lifetime oral sex partners (OR = 2.25, 95% CI 1.42, 3.58). Cancer of the tonsil was associated with four or more lifetime oral sex partners (OR = 3.36, 95 % CI 1.32, 8.53), and, among men, with ever having oral sex (OR = 1.59, 95% CI 1.09, 2.33) and with an earlier age at sexual debut (OR = 2.36, 95% CI 1.37, 5.05). Cancer of the base of the tongue was associated with ever having oral sex among women (OR = 4.32, 95% CI 1.06, 17.6), having two sexual partners in comparison with only one (OR = 2.02, 95% CI 1.19, 3.46) and, among men, with a history of same-sex sexual contact (OR = 8.89, 95% CI 2.14, 36.8). CONCLUSIONS Sexual behaviours are associated with cancer risk at the head and neck cancer subsites that have previously been associated with HPV infection.

Voice problems among teachers: Differences by gender and teaching characteristics

This study describes the effects of teaching activities on voice problems in male (n = 274) and female teachers (n = 280). Over 38% of the teachers studied complained that teaching had an adverse impact on their voice and 39% of those had cut back teaching activities as a result. Compared to males, female teachers more frequently reported a voice problem (38% vs. 26%, p<.05), acute (p<.05), and chronic (p<.05) voice problems, six specific voice symptoms, and five symptoms of physical discomfort. However, there were no gender differences in the perception that a voice problem adversely affected their current or future teaching career. For every type of course taught, women had a higher probability of reporting voice problems compared to men: odds ratio (OR) = 1.7-2.1. Compared with other courses, the teaching of physical education also was associated with an increased risk of developing a voice problem (OR = 3.7, 95% CI: 1.4-9.4) independent of gender, age, hours/day, or years taught. This is the first study to show that in the same occupation, females report a higher frequency of vocal symptoms than males even when teaching characteristics and years employment are similar.

Human papillomavirus and risk of oral cancer

Although human papillomavirus (HPV), a sexually transmitted virus, is established as a necessary cause for more than 95% of cervical carcinomas, the association with oral squamous cell carcinoma is less well delineated. The purpose of this study was to determine the frequency and types of HPV in squamous cells of a group of patients with newly diagnosed oral or pharyngeal cancer (n = 93) compared with an age‐and gender‐frequency‐matched control group of patients with no history of oral cancer (n = 205). HPV was evaluated from a mouth rinse collection of cells in the oral cavity and tested by 32P‐labeled HPV generic probes and DNA sequencing for HPV types. HPV was identified in 15% of the oral cancer cases but in fewer than 5% of the controls (P < .05). The risk of cancer associated with HPV infection was independent of tobacco and alcohol use (adjusted odds ratio [OR] = 3.70; 95% confidence interval [CI]: 1.47–9.32; P < .05). HPV types included similar and other types not identified previously in the genital tract. There was no statistically significant increased risk of cancer among former tobacco users (former vs. never users: adjusted OR = 0.67, 95% CI: 0.31–1.44, P < .05), but the risk was significantly increased for current users (current vs. never: adjusted OR = 2.63; 95% CI: 1.22–5.71; P < .05). Likewise, former alcohol users were not at increased risk of disease (former vs. never: adjusted OR = 1.78; 95% CI: 0.87–3.67), whereas current alcohol users were (current vs. never: adjusted OR = 2.57; 95% CI: 1.22–5.42; P < .05). HPV‐related genital lesions (14.3% vs. 10.6%), oral‐genital sexual behavior (42.4% vs. 45.2%), and number (11 or more) of sexual partners (23% v. 17%) were not significantly different between cases and controls. These data suggest that in addition to tobacco and alcohol, HPV plays a role in the development of oral cancer.