Results br Discussion As reported in other settings a decrea
Discussion As reported in other settings, a decrease in overall incidence and mortality rates for HNC was observed . However, the overall ASIR and ASMR for AGC increased. We hypothesise that trends for HNC are related to the declines in tobacco smoking as a result of the anti-tobacco legislation in SA since 1993 since the alcohol consumption per capita has remained stable at 8 liters [20,32,33]. However the increase in AGC is possibly related to the rising HIV prevalence which is known to increase the risk of HPV infection, persistence and progression cancer . The overall ASIR for HNC are similar to what has been reported previously in SA and other sub-Saharan African countries [34,35]. For the individual HNC, as reported by studies in HIC, there was a trend towards declines in ASIR of OCC and LC, and a similar reduction in ASMR for these cancers [31,36]. However, with OPC the pattern was different to the increases in incidence reported in HIC . While there were declines in incidence, these occurred at a relatively slower rate whilst the ASMR was lower and did not change. The reason for this difference is not clear but could be in part related to the causal role of HPV in OPC. Available data suggests that HPV-related OPC has better prognosis . The ASIR for all three HNC plateaued from 2005 after the introduction of the ART program. This is likely due to improved survival which also provides more time for development of cancer . It is also possible that this was related to the stabilisation of the smoking prevalence rates . Our finding of increased incidence and mortality rates for anal cancer among both males and females confirms reports from HIC [5,6]. This might be related to the concurrent high cervical HPV infection in women and high HIV prevalence [39,40]. As reported elsewhere, rates have continued to increase after the introduction of ART . This may mean that pre-cancerous lesions which are established prior to ART 13(S)-HODE are not reversed by ART and are more likely to persist and accumulate genetic changes. Furthermore, improved survival due to ART provides sufficient time for these lesions to progress undetected in the absence of clear screening guidelines for anal cancer . The ASIR and ASMR for vulval cancers increased, especially among women aged less than 50 years, which confirms previous reports . This suggests an increased role of HPV, exacerbated by the rising HIV prevalence since HPV-related vulval cancers are common in young women . Similar to other settings, the incidence and mortality due to penile cancer has declined . These declines could be related to improvements in penile hygiene secondary to improved access to basic social amenities in the post-apartheid era and reduced prevalence of smoking among men [19,44]. Further future declines are anticipated with the recent expansion of voluntary medical male circumcision. We found that incidence and mortality rates for HNC were higher (at least 2-fold) among men compared to women. This confirms previous reports . Higher rates among men can be explained by the higher prevalence of smoking and alcohol use in men compared to women [4,33]. Indeed, our results for sensitivity analysis showed that the decline in HNC in men was largely related to the decline in smoking prevalence. Studies also show that oropharyngeal HPV infections mirror the gender patterns of OPC . Men have a higher risk of oropharyngeal HPV infection as they are more likely to smoke, with smoking interfering with mucosal immunity, raising their susceptibility to HPV infection . Also, women are more likely to generate antibodies following genital HPV infection than men, with these antibodies offering some protection against oropharyngeal HPV infection . In addition, women have higher genital HPV viral loads, making transmission higher with male-female oral sex than female-male . This implies that men have a higher risk of HPV infection from oral sex when compared to females. The role of HPV in OPC is partly supported by our finding that the median age at diagnosis of OPC was 4 years lower than that of LC as HPV-related OPC is common among younger men [31,37].