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).

Risk factors in oral and oropharyngeal squamous cell carcinoma: a population-based case-control study in southern Sweden.

In the year 2002, about 275,000 inhabitants around the world developed oral cancer and over half of them will die of their disease within 5 years. Oral and oropharyngeal squamous cell carcinoma (OOSCC) accounts for about 1% of all cancers in Sweden - which is low compared to the incidence on the Indian subcontinent and in other parts of Asia, where it is one of the most common forms of cancer. The incidence in Sweden is increasing, however. The study comprised 80% (132/165) of all consecutive cases living in the Southern Healthcare Region, born in Sweden and without previous cancer diagnosis (except skin cancer), who were diagnosed with OOSCC during the period September 2000 to January 2004. Using the Swedish Population Register, 396 cancer-free controls were identified and matched by age, gender and county. Of these individuals, 320 (81%) agreed to take part in the study. Cases and controls were subjected to a standardised interview, identical oral examinations including panoramic radiographs, and cell sampling for human papillomavirus (HPV) analysis. In total 128 patients with planned curative treatment were followed for a median time of 22 months (range 0 - 36). The aims were to assess different potential risk factors in OOSCC such as oral hygiene, dental status, oral mucosal lesions, alcohol and tobacco use, virus infection, and some related to lifestyle. A further aim was to assess the influence of these factors on recurrence or occurrence of a new second primary tumour (SPT) of squamous cell carcinoma. In multivariate analysis 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), more than 5 defective teeth (OR 3.1; 95% CI 1.2-8.2) and more than 20 teeth missing (OR 3.4; 95% CI 1.4-8.5), as well as defective or malfunctioning complete dentures (OR 3.8; 95 % CI 1.3-11.4) were identified as significant risk factors for development of OOSCC. Regular dental care reduced the risk of OOSCC (OR 0.4; 95% CI 0.2-0.6). The cases reported a higher consumption of alcohol than the controls. More than 350 g of alcohol per week (OR 2.6; 95% CI 1.3-5.4) and 11-20 cigarettes per day (OR 2.4; 95% CI 1.3-4.1) were dose-dependent risk factors. The results showed a tendency for women to have a greater risk (OR 1.8) than men at any given level of tobacco consumption. There was no increased risk of OOSCC among users of Swedish moist snuff. There was a significant relationship between high-risk human papillomavirus (HPV) infection and OOSCC (OR 63; 95% CI 14-280). Forty-seven of the cases (36%) were high-risk HPV infected and 7 (5.3%) were low-risk HPV infected in the specimens collected from the oral cavity. The corresponding figures for the controls were 3 (0.94%) and 13 (4.1%), respectively. The high-risk HPV types found in the oral cavity were the same types as observed in cervical cancer. Tumour stage was associated with both higher relative rate (RR) of recurrence or second primary tumour (SPT) of squamous cell carcinoma, and death in intercurrent diseases (DICD), defined as death before the occurrence of recurrence or SPT. High-risk HPV infected patients had an almost threefold increased RR of recurrence/SPT, but seemingly a lower RR of DICD compared to high-risk negative cases. Patients with tonsillar carcinoma had a significantly higher cause-specific RR of recurrence/SPT (RR 2.06; CI 0.99 - 4.28) compared to patients with OSCC of other sites. High alcohol consumption was associated with a high RR of recurrence/SPT, but not with DICD. There was no increased RR of recurrence/SPT related to smoking, but an association between smoking and DICD. In conclusion, the results in this study confirm that both smoking tobacco and alcohol consumption are risk factors for OOSCC. The use of Swedish moist snuff had no effect on the risk. Independent risk factors identified are poor oral hygiene, inadequate dental status and malfunctioning complete dentures. Regular dental check-ups are a preventive factor. Among other possible risk factors studied, high-risk HPV infection appears to be the strongest. High-risk HPV infection increases the cause-specific RR of recurrence or SPT. Tumour stage influences the rate of recurrence/SPT.

High-risk HPV and survival in patients with oral and oropharyngeal squamous cell carcinoma - 5-year follow up of a population-based study.

CONCLUSION: No statistically significant 5-year survival difference was seen in patients with oral and oropharyngeal squamous cell carcinoma (OOPSCC) between high-risk HPV-positive and -negative groups in this population-based study. OBJECTIVES: To see if the formerly observed higher risk for recurrence or second primary tumour (SPT) in high-risk HPV-positive patients with OOPSCC corresponds to worse survival. METHODS: A total of 128 consecutive, previously untreated patients with OOPSCC, who were part of a population-based case-control study in southern Sweden during 2000-2004, were included. A mouthwash sample was collected and exfoliated cells were collected with cotton-tipped swabs from the tonsillar fossa and the tumour. Specimens were analysed for HPV DNA using nested polymerase chain reaction (PCR). Disease-specific survival (DSS) and DSS difference between HPV-negative and HPV-positive patients were calculated. The relationship between age, stage, high-risk HPV status and DSS was assessed. Oral and oropharyngeal tumours were assessed separately. RESULTS: Mean DSS in months was 80.7/68.6 (high-risk HPV-negative/high-risk HPV-positive) for oral cavity tumours (p = 0.18) and 67.6/78.3 (high-risk HPV-negative/high-risk HPV-positive) for oropharyngeal tumours (p = 0.47). For oral cavity tumours, age, T status, N status and stage all showed significant differences in DSS. For oropharyngeal tumours, no significant difference regarding DSS was found.