Single Nucleotide Polymorphism Directed Antiemetic Treatment in Women With Breast Cancer Treated With Neo- or Adjuvant Chemotherapy: A Randomised Multicentre Phase II Study. (EudraCT: 2015-000658-39).

BACKGROUND/AIM: The role of single nucleotide polymorphisms (SNPs) in the frequency and intensity of chemotherapy-induced nausea and vomiting (CINV) in women with breast cancer (BC) is unclear. The primary purpose of this study was to compare/evaluate the effect of SNP-guided antiemetic treatment versus standard CINV treatment. PATIENTS AND METHODS: A randomised, factorial, phase II multicentre study design was used. Women planned for neoadjuvant or adjuvant chemotherapy with epirubicin, cyclophosphamide and fluorouracil (FEC /EC, with or without fluorouracil) for BC were randomised to SNP-guided antiemetic treatment (based on the results of SNP analyses) versus standard CINV treatment. Blood samples were taken before the treatment was initiated. Patient-reported data on CINV (during 10 days from onset of cancer treatment) and health-related quality of life (HRQoL), were collected before and after the first cancer treatment. RESULTS: A total of 188 women were included. Overall, nausea was reported by 86% (n=129) of the patients during the ten-day period from the start of cancer treatment. The SNP genotype studied varied. In FAS-CD95, the genotypes AG and GG were overrepresented; in RB1-LPAR6, GG was overrepresented, and in CCL2, both AA and GG were overrepresented. We found no statistically significant difference in CINV between SNP-guided antiemetic treatment versus standard CINV treatment. CONCLUSION: SNP-guided antiemetic treatment could be as effective as standard treatment. SNP-guided antiemetic treatment of CINV is possibly useful in detecting patients with a higher or lower risk for CINV and thus may help in avoiding over-treatment with toxic components. CINV negatively affects the HRQL.

Recurrence in patients with oral and oropharyngeal squamous cell carcinoma: human papillomavirus and other risk factors.

CONCLUSIONS: The results confirm that tumour stage influences the risk of recurrence/second primary tumour (SPT). High-risk human papillomavirus (HPV)-infected patients have a significantly higher risk of recurrence/SPT compared with high-risk HPV-negative patients. High alcohol consumption was associated with a higher risk of recurrence/SPT. In this study, the competing risk of death in intercurrent disease (DICD) was given special consideration. OBJECTIVES: The aim of the present study was to evaluate whether any of the factors which were found to increase the risk of oral and oropharyngeal squamous cell carcinoma (OOSCC) in previous analyses (smoking tobacco, alcohol, high-risk HPV infection, oral hygiene, missing teeth and dentures) have an influence on recurrence or the occurrence of a new SPT of OOSCC within the first 3 years following diagnosis. PATIENTS AND METHODS: One hundred and twenty-eight consecutive cases with planned curative treatment, who were part of a population-based case-control study carried out in southern Sweden between September 2000 and January 2004, were included. Only patients for whom the intention was curative treatment were eligible. The cases were followed to the first event of recurrence/SPT, death, loss to follow-up, 30 June 2005 or a maximum of 3 years. Time to the first event of recurrence/SPT was analysed by cumulative incidence, where DICD was a competing risk. Regression was performed on cause-specific hazard rates. RESULTS: After a median follow-up time of 22 months (range 0-36 months), 30 recurrences, 2 SPT, 12 lost to follow-up and 21 deaths before recurrence or SPT were observed. Tumour stage was associated with both a higher risk of recurrence/SPT and of DICD. In univariate analysis, patients with tonsillar carcinoma had a significantly higher risk of recurrence/SPT than patients with carcinoma at other sites, but there was no difference according to site in multivariate analyses. High alcohol consumption was associated with a higher risk of recurrence/SPT, but not of DICD. There was no increased risk of recurrence/SPT related to smoking, but there was an association between smoking and DICD. High-risk HPV-positive cases had a higher risk of recurrence/SPT, but a lower risk of DICD compared with high-risk HPV-negative cases. This seemingly higher risk should be interpreted by taking the competing risk of DICD into account.

Oral status, oral infections and some lifestyle factors as risk factors for oral and oropharyngeal squamous cell carcinoma. A population-based case-control study in southern Sweden.

CONCLUSION: Our results show that average and poor oral hygiene and inadequate dental status are independent risk factors for oral and oropharyngeal squamous cell carcinoma (OOSCC), irrespective of tobacco and alcohol consumption. OBJECTIVE: To evaluate a possible relationship between oral cancer, oral hygiene, dental status, oral mucosal lesions and some lifestyle factors in a population-based case-control study. MATERIAL AND METHODS: Between September 2000 and January 2004, 132/165 (80%) of all incident cases of OOSCC and 320/396 (81%) of the intended eligible matched controls participated in the study. Cases and controls were subjected to an identical oral examination. A standardized protocol specially designed for the study was used. RESULTS: After adjusting for tobacco and alcohol consumption, average oral hygiene (OR 2.0; 95% CI 1.1-3.6) and poor oral hygiene (OR 5.3; 95% CI 2.5-11.3) emerged as significant risk factors for OOSCC. More than 20 lost teeth (OR 3.4; 95% CI 1.4-8.5), >5 defective teeth (OR 3.1; 95% CI 1.2-8.2) and poorly fitting or defective complete dentures (OR 3.8; 95% CI 1.3-11.4) were significant risk factors. Regular dental check-ups were associated with a decreased risk of OOSCC (OR 0.4; 95% CI 0.2-0.6).

Strong association between infection with human papillomavirus and oral and oropharyngeal squamous cell carcinoma: a population-based case-control study in southern Sweden.

CONCLUSIONS: The results of this study demonstrate a strong association between infection with high-risk types of human papillomavirus (HPV) and oral and oropharyngeal squamous cell carcinoma (OOSCC), suggesting that high-risk HPV types play a key role in carcinogenesis. The estimated proportion of OOSCC cases attributable to HPV infection was 35%. OBJECTIVE: HPV appears to have an aetiological role in OOSCC, despite the fact that the reported prevalences of HPV in both OOSCC patients and healthy individuals have varied widely. We aimed to investigate the presence and spectrum of both high- and low-risk HPVs in all consecutive cases of OOSCC in a Swedish healthcare region over a 3-year period and in population-based, matched healthy controls. MATERIAL AND METHODS: A total of 131 patients with OOSCC were studied. Samples taken from the surface of the tumour and from the tonsillar fossa using cotton-tipped swabs were investigated, together with exfoliated cells collected using a mouthwash. Tonsillar fossa and mouthwash specimens were collected in the same way from 320 matched controls. All samples were tested for HPV DNA by nested polymerase chain reaction using the primer pairs MY09/MY11 and GP5 + /GP6+, and in positive cases the HPV type was determined by DNA sequencing. RESULTS: Infection with high-risk HPV was shown to be a strong risk factor for OOSCC (OR = 63; 95% CI 14-480). Forty-seven (36%) of the cancer patients had > or =1 specimen that was positive for a high-risk HPV type (81% of which were HPV 16), while only 3 (0.94%) of the controls were positive for a high-risk HPV type. Seven (5.3%) of the cancer patients and 13 (4.1%) of the controls were positive for any of the mucosal, mucocutaneous or cutaneous low-risk HPV types.

Use of Swedish moist snuff, smoking and alcohol consumption in the aetiology of oral and oropharyngeal squamous cell carcinoma. A population-based case-control study in southern Sweden.

CONCLUSIONS: The results of this study confirm that both smoking of tobacco and alcohol consumption are risk factors for oral and oropharyngeal squamous cell carcinoma (OOSCC). The use of moist snuff had no effect on the risk of OOSCC, probably due to the low levels of tobacco-specific N-nitrosamines in Swedish moist snuff. OBJECTIVE: The aims of this population-based case-control study in southern Sweden were to establish risk estimates for cigarette and alcohol consumption and to evaluate whether Swedish moist snuff is a risk factor for OOSCC. MATERIAL AND METHODS: Between September 2000 and January 2004, 132/165 consecutive cases (80%) diagnosed with OOSCC and 320/396 matched controls (81%) were investigated. All subjects were interviewed and examined according to a standardized protocol. RESULTS: Individuals who drank > or =350 g of alcohol/week showed an increased risk of OOSCC (OR 2.6; 95% CI 1.3-5.4). Total lifetime consumption of tobacco for smoking (>250 kg) had a dose-response effect on the risk of OOSCC (OR 4.7; 95% CI 2.4-9.1). We found no increased risk of OOSCC associated with the use of Swedish moist snuff (OR 1.1; 95% CI 0.5-2.5).

Should the European Union lift the ban on snus? Evidence from the Swedish experience.

The very low smoking prevalence in Sweden has received considerable attention. Sweden was the only country in Europe to reach the World Health Organizations' goal of less than 20% daily smoking prevalence among adults by year 2000. Only 17% of Swedish men smoke. Some have argued that this has been achieved because Swedes use another form of tobacco instead. Sweden has a high level of use of a moist snuff product called 'snus'. Nineteen per cent of adult men and 1% of women are daily users and the trend is increasing. Epidemiological studies have failed to find evidence that snus causes cancers, including oral cancer. Its adverse effects on the cardiovascular system are debated, but are certainly less than those of smoking. Recent studies among former smokers indicate that many men have quit smoking using snus. Forty-seven per cent of current snus users are former smokers and 28% of ex-smoking used snus at their last attempt to stop smoking. The association between high snus consumption and low smoking prevalence has been debated and challenged. It has been argued that snus may be a gateway to cigarette smoking. Recent data has found that among those starting tobacco use in the form of snus, 20% later go on to smoking while the same risk for those not starting with snus is 43%. On balance, there is reason to believe that having snus available to the Swedish population has been of benefit to public health. Repealing the ban on snus in the rest of the European Union might also have some positive effect, depending on the marketing.