Investigating the effect of sexual behaviour on oropharyngeal cancer risk: a methodological assessment of Mendelian randomization.

BACKGROUND: Human papilloma virus infection is known to influence oropharyngeal cancer (OPC) risk, likely via sexual transmission. However, sexual behaviour has been correlated with other risk factors including smoking and alcohol, meaning independent effects are difficult to establish. We aimed to evaluate the causal effect of sexual behaviour on the risk of OPC using Mendelian randomization (MR). METHODS: Genetic variants robustly associated with age at first sex (AFS) and the number of sexual partners (NSP) were used to perform both univariable and multivariable MR analyses with summary data on 2641 OPC cases and 6585 controls, obtained from the largest available genome-wide association studies (GWAS). Given the potential for genetic pleiotropy, we performed a number of sensitivity analyses: (i) MR methods to account for horizontal pleiotropy, (ii) MR of sexual behaviours on positive (cervical cancer and seropositivity for Chlamydia trachomatis) and negative control outcomes (lung and oral cancer), (iii) Causal Analysis Using Summary Effect estimates (CAUSE), to account for correlated and uncorrelated horizontal pleiotropic effects, (iv) multivariable MR analysis to account for the effects of smoking, alcohol, risk tolerance and educational attainment. RESULTS: In univariable MR, we found evidence supportive of an effect of both later AFS (IVW OR = 0.4, 95%CI (0.3, 0.7), per standard deviation (SD), p = < 0.001) and increasing NSP (IVW OR = 2.2, 95%CI (1.3, 3.8) per SD, p = < 0.001) on OPC risk. These effects were largely robust to sensitivity analyses accounting for horizontal pleiotropy. However, negative control analysis suggested potential violation of the core MR assumptions and subsequent CAUSE analysis implicated pleiotropy of the genetic instruments used to proxy sexual behaviours. Finally, there was some attenuation of the univariable MR results in the multivariable models (AFS IVW OR = 0.7, 95%CI (0.4, 1.2), p = 0.21; NSP IVW OR = 0.9, 95%CI (0.5 1.7), p = 0.76). CONCLUSIONS: Despite using genetic variants strongly related sexual behaviour traits in large-scale GWAS, we found evidence for correlated pleiotropy. This emphasizes a need for multivariable approaches and the triangulation of evidence when performing MR of complex behavioural traits.

A survey on the cost of oral surgery dental speciality training.

Background Following graduation, training costs for an individual trainee to achieve completion of specialist surgical training has been estimated to be between £20,000 to £71,431, and is expected to rise. Furthermore, there are other non-monetary costs to consider, including poor work-life balance and the burden of training on home life.Methods A 22-question online survey using SurveyGizmo was developed and emailed to all current UK and Ireland oral surgery trainees from 2016-2019. The survey consisted of open free text, binomial and variable scale responses related to the cost of training.Results A total of 43 (96%) oral surgery trainees responded to the survey. Sixty-eight percent had enrolled on a postgraduate degree, or other higher qualification, during their training. Of these, only 4.5% were fully funded and nearly half received no funding at all. Trainees reported vast disparities in financial support across deaneries, with an overall average study budget of £687. Annual obligatory costs of up to £4,142 and a mean average spend of £9,240 on courses and £2,830 on conferences were reported. Childcare, relocating and textbooks were listed as additional costs incurred.Conclusion A standardised, transparent and more substantial financial support system is required for dental specialty trainees.