Oral human papillomavirus infection incidence and clearance: a systematic review of the literature.

Subclinical oral human papillomavirus (HPV) infection that persists for decades is likely to precede an HPV-driven squamous cell carcinoma of the head and neck, but little is known about the natural history of oral HPV. We systematically reviewed and abstracted data from nine manuscripts that examined human immunodeficiency virus-negative and cancer-free subjects for oral HPV DNA to determine the pooled baseline prevalence and incidence of newly acquired oral HPV infections, and specifically for HPV-16. We also documented the clearance rate and the median time to clearance, where data existed. Of 3762 individuals, 7.5 % had an oral infection with any HPV type (1.6 % for HPV-16). Meta-regression analysis estimated the 12-month cumulative incidence to be 4.8 % (95 % confidence interval 3.2-7.3 %). The overall oral HPV clearance was reported to be 0-80 % between studies, and the median time to clearance from 6.5 to 18 months. Oral HPV-16 clearance was 43-83 %, and median time to clearance for HPV-16 was 7-22 months. Oral HPV prevalence, incidence and clearance vary considerably between published studies from different geographical regions. Further research is required to identify predictors of persistent oral HPV infection. Measurable baseline prevalence was observed in all studies, as well as non-trivial incidence of newly acquired oral HPV infections and incomplete clearance.

Cancers in Australia in 2010 attributable to the consumption of alcohol.

OBJECTIVE: To estimate the proportion and numbers of cancers occurring in Australia in 2010 that are attributable to alcohol consumption. METHODS: We estimated the population attributable fraction (PAF) of cancers causally associated with alcohol consumption using standard formulae incorporating prevalence of alcohol consumption and relative risks associated with consumption and cancer. We also estimated the proportion change in cancer incidence (potential impact fraction [PIF]) that might have occurred under the hypothetical scenario that an intervention reduced alcohol consumption, so that no-one drank >2 drinks/day. RESULTS: An estimated 3,208 cancers (2.8% of all cancers) occurring in Australian adults in 2010 could be attributed to alcohol consumption. The greatest numbers were for cancers of the colon (868) and female breast cancer (830). The highest PAFs were for squamous cell carcinomas of the oral cavity/pharynx (31%) and oesophagus (25%). The incidence of alcohol-associated cancer types could have been reduced by 1,442 cases (4.3%)--from 33,537 to 32,083--if no Australian adult consumed >2 drinks/day. CONCLUSIONS: More than 3,000 cancers were attributable to alcohol consumption and thus were potentially preventable. IMPLICATIONS: Strategies that limit alcohol consumption to guideline levels could prevent a large number of cancers in Australian adults.

Cancers in Australia in 2010 attributable to total breastfeeding durations of 12 months or less by parous women.

OBJECTIVES: To estimate the proportion and number of cancers occurring in Australia in 2010 attributable to parous women having breastfed for total durations of ≤12 months. METHODS: We estimated the population attributable fraction (PAF) of breast cancers (the only cancer site with convincing evidence of causal association) associated with women breastfeeding for ≤12 months in total, using standard formulae incorporating breastfeeding prevalence data, relative risks associated with breastfeeding and cancer incidence. We also estimated the proportion change in disease incidence (potential impact fraction [PIF]) that might have occurred under two hypothetical scenarios of women breastfeeding for longer durations. RESULTS: An estimated 235 (1.7%) breast cancer cases that occurred in Australian in 2010 could be attributed to women breastfeeding for total durations of ≤12 months. Assuming a hypothetical increase in breastfeeding, we estimated that the number of breast cancers prevented would range from 36 to 51 (prevented fraction = 0.3% to 0.4%). CONCLUSIONS: More than 200 breast cancers were attributable to women breastfeeding for total durations of ≤12 months. IMPLICATIONS: Policies to increase breastfeeding duration may help prevent breast cancers in the future.

Cancers in Australia in 2010 attributable to inadequate consumption of fruit, non-starchy vegetables and dietary fibre.

OBJECTIVES: To estimate the number and proportion of cancers occurring in Australia in 2010 attributable to consumption deficits in fruit, non-starchy vegetables and dietary fibre. METHODS: We estimated the population attributable fraction (PAF) for cancers causally associated with inadequate intake of fruit and non-starchy vegetables (oral cavity, pharynx, oesophageal squamous cell carcinoma, stomach, larynx); inadequate intake of fruit (lung); and insufficient intake of fibre (colorectum). We used standard formulae incorporating prevalence of exposure (1995 National Nutrition Survey) and relative risks from independent studies. RESULTS: Overall, 1,555 (1.4% of all) and 311 (0.3% of all) cancers were attributable to inadequate intakes of fruit and non-starchy vegetables, respectively. A further 2,609 colorectal cancers (18% of colorectal) were attributable to insufficient fibre intake. If Australians increased their fibre intake by eating the recommended daily intakes of fruit and vegetables, an estimated 1,293 (8.8%) colorectal cancers could be prevented. CONCLUSIONS: One in six colorectal cancer cases was attributable to inadequate intake of dietary fibre and about 1,800 cancers at other sites were attributable to insufficient fruit and non-starchy vegetable consumption. IMPLICATIONS: Increasing the proportion of Australians who consume the recommended intake of fruit, vegetables and fibre could prevent up to 4% of all cancers.

Cancers in Australia in 2010 attributable to the consumption of red and processed meat.

OBJECTIVES: To estimate the proportion and numbers of cancers in Australia in 2010 attributable to consuming red/processed meat. METHODS: We estimated the population attributable fraction (PAF) for cancers causally associated with red/processed meat consumption (colon, rectum) using standard formulae incorporating prevalence of consumption (1995 National Nutrition Survey), relative risks associated with consumption and cancer incidence. We also estimated the proportion change in cancer incidence (potential impact fraction [PIF]) that might have occurred under two hypothetical interventions whereby Australian adults reduced their consumption of red/processed meat from prevailing levels to ≤100 g or ≤65 g per day, respectively. RESULTS: An estimated 2,614 cases (18%) of colorectal cancer occurring in Australians in 2010 were attributable to red/processed meat consumption (16% of colon cancers; 23% of rectal cancers). We estimated that if all Australian adults had consumed ≤65 g/day or ≤100 g/day of red/processed meat, then the incidence of colorectal cancer would have been 5.4% (798 cancers) or 1.4% (204 cancers) lower, respectively. CONCLUSIONS: About one in six colorectal cancers in Australians in 2010 were attributable to red/processed meat consumption. IMPLICATIONS: Reducing red/processed meat intake may reduce colorectal cancer incidence, but must be balanced against nutritional benefits of modest lean meat consumption.

Cancers prevented in Australia in 2010 through the consumption of aspirin.

OBJECTIVES: To estimate the proportion and number of cancers in Australia in 2010 that may have been prevented from occurring due to daily use of aspirin in the population. METHODS: We calculated the Prevented Fraction (PF) of colorectal and oesophageal cancers using standard formulae. The PF is the proportion of the hypothetical total load of cancer in the population that was prevented by exposure to aspirin. The formula incorporates estimates of the prevalence of aspirin use in Australian adult populations, the relative risks associated with aspirin use and cancer incidence. RESULTS: An estimated 335 colorectal cancers, 22 oesophageal adenocarcinomas and 29 oesophageal squamous cell carcinomas (SCC) were potentially prevented due to daily aspirin use. These figures equate to 2.2%, 3.1% and 5.4% of all colorectal cancers, oesophageal adenocarcinomas and oesophageal SCCs, respectively, that would otherwise have occurred but were potentially avoided due to the daily use of aspirin pertaining in the Australian population. CONCLUSIONS: At current levels of consumption, a small but measurable reduction in cancer incidence can be attributed to daily aspirin use. IMPLICATIONS: Assuming the benefits outweigh the harms of known gastrointestinal toxicity and other hazards, aspirin use may be considered for some people to prevent the development of particular gastrointestinal cancers.

Cancers in Australia in 2010 attributable to and prevented by the use of menopausal hormone therapy.

OBJECTIVES: To estimate the proportion and number of cancers occurring in Australia in 2010 attributable to menopausal hormone therapy (MHT) use. METHODS: We estimated the population attributable fraction for cancers causally associated with MHT (breast, endometrium, ovary), and the proportion of colorectal cancers prevented by MHT. We used standard formulae incorporating Australian prevalence data, relative risks of cancer associated with MHT and cancer incidence. We also estimated potential change in cancer incidence under two hypothetical scenarios whereby 25% fewer Australian women used MHT, or women exclusively used oestrogen-only MHT. RESULTS: An estimated 539 cancers in Australia in 2010 were attributable to MHT: 453 breast, 67 endometrial and 19 ovarian cancers equating to 3.4%, 3.1% and 1.6% of each cancer type, respectively. In contrast, MHT may have prevented 52 colorectal cancers. If 25% fewer women used MHT, then 141 cancers may have been avoided. If women exclusively used oestrogen-only MHT then 240 cancers may have been avoided. CONCLUSIONS: MHT use caused more than 500 cancers in Australian women in 2010 and prevented ∼50 colorectal cancers. IMPLICATIONS: MHT use continues to cause an excess of cancers. The risks, benefits, regimen and treatment duration should be carefully considered for each woman before MHT is commenced.

Cancers in Australia in 2010 attributable to modifiable factors: introduction and overview.

OBJECTIVE: To describe the approach underpinning a national project to estimate the numbers and proportions of cancers occurring in Australia in 2010 that are attributable to modifiable causal factors. METHODS: We estimated the population attributable fraction (PAF) (or prevented fraction) of cancers associated with exposure to causal (or preventive) factors using standard formulae. Where possible, we also estimated the potential impact on cancer incidence resulting from changes in prevalence of exposure. Analyses were restricted to factors declared causal by international agencies: tobacco smoke; alcohol; solar radiation; infectious agents; obesity; insufficient physical activity; insufficient intakes of fruits, vegetables and fibre; red and processed meat; menopausal hormone therapy (MHT); oral contraceptive pill (OCP); and insufficient breast feeding. Separately, we estimated numbers of cancers prevented by: aspirin; sunscreen; MHT; and OCP use. We discuss assumptions pertaining to latent periods between exposure and cancer onset, choices of prevalence data and risk estimates, and approaches to sensitivity analyses. RESULTS: Numbers and population attributable fractions of cancer are presented in accompanying papers. CONCLUSIONS: This is the first systematic assessment of population attributable fractions of cancer in Australia.

Cancers in Australia in 2010 attributable to infectious agents.

OBJECTIVES: To estimate the proportion and numbers of cancers in Australia in 2010 attributable to infectious agents. METHODS: The population attributable fraction (PAF) and number of cancers caused by hepatitis B and C viruses (HBV, HCV), Helicobacter pylori and human immunodeficiency virus (HIV) were calculated using standard formulae incorporating prevalence of infection in the Australian population, the relative risks associated with that infection and cancer incidence. For cancers with very strong associations to the infectious agent (Epstein-Barr virus [EBV], human papillomavirus [HPV] and HIV/Kaposi's sarcoma herpes virus [KSHV]), calculations were based on viral prevalence in the tumour. RESULTS: An estimated 3,421 cancers (2.9% of all cancers) in Australia in 2010 were attributable to infections. Infectious agents causing the largest numbers of cancers were HPV (n=1,706), H. pylori (n=793) and HBV/HCV (n=518). Cancer sites with the greatest number of cancers caused by infections were cervix (n=818), stomach (n=694) and liver (n=483). Cancers with highest proportions attributable to infectious agents were Kaposi's sarcoma (100%), cervix (100%), nasopharynx (87%), anus (84%) and vagina (70%). CONCLUSIONS: Infectious agents cause more than 3,000 cancers annually in Australia. IMPLICATIONS: Opportunities for cancer prevention through infection control are considerable, even in a 'first world' nation like Australia.

Cancers in Australia in 2010 attributable to overweight and obesity.

OBJECTIVES: To estimate the proportion and number of cancers occurring in Australia in 2010 attributable to overweight/obesity. METHODS: We estimated the population attributable fraction (PAF) and number of cancers causally associated with overweight/obesity. We used standard formulae incorporating Australian prevalence data for body mass index (BMI), relative risks associated with BMI and cancer. We also estimated the proportion change in cancer incidence (potential impact fraction [PIF]) that may have occurred assuming that the prevalence of overweight/obesity had remained at 1990 levels. RESULTS: An estimated 3,917 cancer cases (3.4% of all cancers) diagnosed in 2010 were attributable to overweight/obesity, including 1,101 colon cancers, 971 female post-menopausal breast cancers and 595 endometrial cancers (PAFs of 10%, 8% and 26%, respectively). Highest PAFs were observed for oesophageal adenocarcinoma (31%), endometrial cancer (26%) and kidney cancer (19%). If the prevalence of overweight/obesity in Australia had remained at levels prevailing in 1990, we estimate there would have been 820 fewer cancers diagnosed in 2010 (PIF 2%). CONCLUSIONS: Overweight/obesity causes a substantial number of cancers in Australia. IMPLICATIONS: Public health strategies to reduce the prevalence of overweight and obesity will reduce the incidence of cancer, particularly of the colon, breast and endometrium.

Cancers in Australia in 2010 attributable to insufficient physical activity.

OBJECTIVES: To estimate the proportion and numbers of cancers occurring in Australia in 2010 attributable to insufficient levels of physical activity. METHODS: We estimated the population attributable fraction (PAF) of cancers causally associated with insufficient physical activity (colon, post-menopausal breast and endometrium) using standard formulae incorporating prevalence of insufficient physical activity (<60 minutes at least 5 days/week), relative risks associated with physical activity and cancer incidence. We also estimated the proportion change in cancer incidence (potential impact fraction [PIF]) that may have occurred assuming that everyone with insufficient activity levels increased their exercise by 30 minutes/week. RESULTS: An estimated 1,814 cases of colon, post-menopausal breast and endometrial cancer were attributable to insufficient levels of physical activity: 707 (6.5%) colon; 971 (7.8%) post-menopausal breast; and 136 (6.0%) endometrial cancers. If those exercising below the recommended level had increased their activity level by 30 minutes/week, we estimate 314 fewer cancers (17% of those attributable to insufficient physical activity) would have occurred in 2010. CONCLUSIONS: More than 1,500 cancers were attributable to insufficient levels of physical activity in the Australian population. IMPLICATIONS: Increasing the proportion of Australians who exercise could reduce the incidence of several common cancers.

Cancers in Australia in 2010 attributable to tobacco smoke.

OBJECTIVES: To estimate the population attributable fraction (PAF) and numbers of cancers occurring in Australia in 2010 attributable to tobacco smoking, both personal and by a partner. METHODS: We used a modified Peto-Lopez approach to calculate the difference between the number of lung cancer cases observed and the number expected assuming the entire population developed lung cancer at the same rate as never smokers. For cancers other than lung, we applied the standard PAF formula using relative risks from a large cohort and derived notional smoking prevalence. To estimate the PAF for partners' smoking, we used the standard formula incorporating the proportion of non-smoking Australians living with an ever-smoking partner and relative risks associated with partner smoking. RESULTS: An estimated 15,525 (13%) cancers in Australia in 2010 were attributable to tobacco smoke, including 8,324 (81%) lung, 1,973 (59%) oral cavity and pharynx, 855 (60%) oesophagus and 951 (6%) colorectal cancers. Of these, 136 lung cancers in non-smokers were attributable to partner tobacco smoke. CONCLUSIONS: More than one in eight cancers in Australia is attributable to tobacco smoking and would be avoided if nobody smoked. IMPLICATIONS: Strategies to reduce the prevalence of smoking remain a high priority for cancer control.

Cancers in Australia in 2010 attributable to and prevented by the use of combined oral contraceptives.

OBJECTIVES: To estimate the proportion and number of cancers occurring in Australia in 2010 attributable to combined oral contraceptive pill (OCP) use. METHODS: We estimated the population attributable fraction (PAF) for cancers causally associated with combined OCP use (breast, cervix), and the proportion of endometrial and ovarian cancers prevented (prevented fraction [PF]). We used standard formulae incorporating prevalence of combined OCP use in the Australian population, relative risks of cancer associated with this exposure and cancer incidence. RESULTS: An estimated 105 breast and 52 cervical cancers (0.7% and 6.4% of each cancer, respectively) in Australia in 2010 were attributable to current use of combined OCP. Past combined OCP use was estimated to have prevented 1,032 endometrial and 308 ovarian cancers in 2010, reducing the number of cancers that would otherwise have occurred by 31% and 19%, respectively. CONCLUSIONS: A small proportion of breast and cervical cancers is attributable to combined OCP use; OCP use is likely to have prevented larger numbers of endometrial and ovarian cancers. IMPLICATIONS: Women seeking contraceptive advice should be told of potential adverse effects, but should also be told that - along with reproductive health benefits - combined OCP use can reduce long-term risks of ovarian and endometrial cancers.

Cancers in Australia attributable to exposure to solar ultraviolet radiation and prevented by regular sunscreen use.

OBJECTIVES: To estimate the proportion and numbers of cancers occurring in Australia attributable to solar ultraviolet radiation (UVR) and the proportion and numbers prevented by regular sun protection factor (SPF) 15+ sunscreen use. METHODS: We estimated the population attributable fraction (PAF) and numbers of melanomas and keratinocyte cancers (i.e. basal cell carcinomas and squamous cell carcinomas) due to exposure to ambient UVR resulting from residing in Australia versus residing in the UK (for melanoma) or Scandinavia (for keratinocyte cancers). We also estimated the prevented fraction (PF): the proportion of cancers that would have occurred but were likely prevented by regular sunscreen use. RESULTS: An estimated 7,220 melanomas (PAF 63%) and essentially all keratinocyte cancers occurring in Australia were attributable to high ambient UVR levels in Australia. We estimated that regular sunscreen use prevented around 14,190 (PF 9.3%) and 1,730 (PF 14%) people from developing SCC and melanoma, respectively. CONCLUSIONS: Although our approach was conservative, a high proportion of skin cancers in Australia are attributable to high ambient levels of UVR. Prevailing levels of sunscreen use probably reduced skin cancer incidence by 10-15%. IMPLICATIONS: Most skin cancers are preventable. Sunscreen should be a component of a comprehensive sun protection strategy.

Cancers in Australia in 2010 attributable to modifiable factors: summary and conclusions.

OBJECTIVE: To estimate the numbers and proportions of cancers occurring in Australia in 2010 attributable to modifiable causal factors. METHODS: We estimated the population attributable fraction (PAF) of cancers associated with exposure to 13 causal factors using standard formulae incorporating exposure prevalence and relative risk data. We also calculated the potential impact of changing exposure to some factors. RESULTS: A total of 32% of all cancers diagnosed in Australia in 2010 (excluding keratinocyte cancers) were attributable to the 13 factors assessed (men 33%; women 31%). Leading factors were tobacco smoke (PAF all cancers: 13.4%), solar radiation (6.2%), inadequate diet (6.1%) and overweight/obesity (3.4%). Factors conferring highest PAFs differed by sex: highest PAFs for men were tobacco smoke (15.8%), solar radiation (7.1%) and alcohol (3.0%); while highest PAFs for women were tobacco smoke (10.1%), solar radiation (5.0%) and overweight/obesity (4.5%). Sites with the highest counts of potentially preventable cancers were lung (8,569), colorectal (7,404), melanoma of the skin (7,220) and breast (3,233). CONCLUSIONS: At least one in three cancers in Australia is attributable to exposure to known modifiable factors. IMPLICATIONS: Up to 37,000 cancers could be prevented in Australia each year if the population avoided exposure to 13 common factors known or strongly suspected to cause cancer.

Dietary antioxidants and risk of Barrett's esophagus and adenocarcinoma of the esophagus in an Australian population.

While dietary antioxidants are emerging as potentially modifiable risk factors for esophageal adenocarcinoma (EAC), studies on dietary antioxidants and its precursor Barrett's esophagus (BE) are limited. The present study extends previous work on BE by investigating risks of nondysplastic BE, dysplastic BE and EAC associated with intake of antioxidants such as vitamin C, vitamin E, ß-carotene, and selenium. Age and sex matched control subjects (n=577 for BE; n=1,507 for EAC) were sampled from an Australian population register. Information on demography, and well established EAC risk factors were obtained using self-administered questionnaires. Intake of antioxidants for patients newly diagnosed with nondysplastic BE (n=266), dysplastic BE (n=101), or EAC (n=299), aged 18-79 years, were obtained using a food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable adjusted logistic regression models. High intake of ß-carotene from food and supplement sources combined was inversely associated with risk of dysplastic BE (OR Q4 vs. Q1=0.45; 95%CI: 0.20-1.00). High intake of vitamin E from food sources (OR Q4 vs. Q1=0.43; 95%CI: 0.28-0.67), from food and supplements combined (OR Q4 vs. Q1=0.64; 95%CI: 0.43-0.96), and a high antioxidant index score were inversely associated with risk of EAC. We found no significant trends between intake of ß-carotene, vitamin C, vitamin E, and selenium and risk of nondysplastic or dysplastic BE. However, our data suggest that a high intake of ß-carotene may be associated with decreased risk of dysplastic BE.

Tea consumption and risk of ovarian cancer.

OBJECTIVE: Although the growth inhibitory effects of tea, particularly green tea, and tea polyphenols have been demonstrated in animal models of ovarian cancer, the results of epidemiological studies have been inconclusive. METHODS: We investigated this issue using data from an Australian population-based, case-control study (1,368 cases; 1,416 controls). We also systemically reviewed all the available evidence regarding the potential association between green tea and risk of ovarian cancer, given the abundance of bioavailable polyphenols and higher antioxidant capacity of green tea than black tea, to provide the best summary estimate of the association. RESULTS: In our case-control study, while we found uniformly inverse odds ratios (OR) for tea drinkers compared to non-tea drinkers [4 + cups/day any tea OR 0.71 (95% CI 0.52-0.97); green tea OR 0.82 (95% CI 0.38-1.79); herbal tea OR 0.77 (95% CI 0.28-2.14): black tea OR 0.88 (95% CI 0.66-1.18)], we saw no dose-response trends. Our meta-analysis provided some evidence that women who drink green tea have a lower risk of ovarian cancer, although the summary estimate did not reach statistical significance (0.58, 95% CI 0.33-1.01 for >or=1 cup/green tea day). This result is consistent with two recent meta-analyses that evaluated the association of tea (all types combined) and ovarian cancer risk. CONCLUSION: Overall, our findings provide some support for the hypothesis that tea consumption reduces the risk of ovarian cancer.

Meat, fish, and ovarian cancer risk: Results from 2 Australian case-control studies, a systematic review, and meta-analysis.

BACKGROUND: Variation in meat and fish intakes has been associated with a risk of some cancers, but evidence for ovarian cancer is limited and inconsistent. OBJECTIVE: We examined the association between intakes of total meat, red meat, processed meat, poultry, and fish and ovarian cancer risk. DESIGN: Data came from 2 Australian population-based case-control studies conducted 10 y apart. Analyses included a total of 2049 cases and 2191 control subjects. We obtained dietary information via a food-frequency questionnaire. We estimated multivariable-adjusted odds ratios (ORs) for each study by using logistic regression and combined results of the 2 studies by using random-effects models. We also assembled the published evidence in a systematic review and meta-analysis. RESULTS: Although there was no association between total or red meat intake and ovarian cancer risk, women with the highest intake of processed meat had a significantly increased risk of ovarian cancer in the 2 case-control studies (combined OR: 1.18; 95% CI: 1.15, 1.21) and the meta-analysis [7 studies; pooled relative risk (RR): 1.20; 95% CI: 1.07, 1.34]. In contrast, a frequent intake of poultry was associated with borderline significant reductions in risk in the 2 case-control studies (combined OR: 0.83; 95% CI: 0.67, 1.03) and the meta-analysis including 7 additional studies (pooled RR: 0.90; 95% CI: 0.79, 1.01). High fish intake was associated with a significantly reduced risk in the 2 case-control studies (combined OR: 0.76; 95% CI: 0.62, 0.94) and a smaller borderline significant reduction in the meta-analysis (6 additional studies; pooled RR: 0.84; 95% CI: 0.68, 1.03). CONCLUSION: Our results suggest that low consumption of processed meat and higher consumption of poultry and fish may reduce the risk of ovarian cancer.

Epithelial ovarian cancer: testing the 'androgens hypothesis'.

In 1998, Risch proposed a hypothesis for the pathogenesis of ovarian cancer relating to the role of androgens in stimulating epithelial cell proliferation. Although this hypothesis has been widely discussed, direct evidence to support it is scant. To address this issue, we have conducted a detailed analysis of factors possibly associated with high circulating levels of androgens, including polycystic ovary syndrome (PCOS), hirsutism and acne (all clinically associated with hyperandrogenism) using the data collected in an Australia-wide, population-based case-control study. Cases aged 18-79 years with a new diagnosis of invasive epithelial ovarian cancer (n=1276) or borderline malignant tumour (n=315) were identified through a network of clinics and cancer registries throughout Australia. Controls (n=1508) were selected from the National Electoral Roll. Women self-reported a history of PCOS, acne, hirsutism and also use of testosterone supplements or the androgenic medication Danazol. We found no evidence that a history of PCOS, acne or hirsutism was associated with ovarian cancer overall, or with specific subtypes, with the exception of serous borderline tumours that were positively associated with a history of PCOS (OR 2.6; 95% CI 1.0-6.1). Women who had ever used testosterone supplements had an increased risk of ovarian cancer (OR 3.7; 95% CI 1.1-12.0); however, use of the androgenic medication Danazol did not increase risk (OR 1.0; 95% CI 0.4-2.9). Overall, our results do not support the hypothesis that androgen-related disorders increase the risk of ovarian cancer.

Betel quid not containing tobacco and oral leukoplakia: a report on a cross-sectional study in Papua New Guinea and a meta-analysis of current evidence.

Leukoplakia is an asymptomatic, potentially malignant change in the oral mucosa. Previous studies have reported that smoking and betel quid chewing are associated with increased risk of leukoplakia; few studies have reported on these associations in populations where betel quid does not contain tobacco. We conducted a case-control study nested in a cross-sectional study in Papua New Guinea and a systematic review of studies that included chewers of betel quid without tobacco. Our study recruited 1,670 adults. We recorded betel quid chewing and smoking. The prevalence of leukoplakia was 11.7%. In the nested case-control study of 197 cases and 1,282 controls, current betel chewing was associated with increased risk of leukoplakia with an adjusted odds ratio for current chewers of 3.8 (95% CI 1.7, 8.4) and in the heaviest chewers of 4.1 (95% CI 1.8, 9.1) compared to non-chewers. Current smoking was associated with an increased risk of leukoplakia with an adjusted odds ratio for current smokers of 6.4 (95% CI 4.1, 9.9) and amongst heaviest smokers of 9.8 (95% CI 5.9, 16.4) compared to non-smokers. The systematic review identified 5 studies examining risk of leukoplakia associated with betel quid chewing in populations where betel quid did not contain tobacco and that controlled for smoking. In studies that adjusted for smoking, the combined random effect odds ratio was 7.9 (95% CI 4.3, 14.6) in betel quid chewers. The results of this study and systematic review of similar studies provide evidence of the role of betel quid not containing tobacco and leukoplakia.