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    2019-08-16


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    Introduction The overall incidence of head and neck cancers (HNC) has declined in recent years in high income countries (HIC) [1]. A closer analysis has shown two patterns: an increasing trend for HPV-related HNC that mainly arise from Fulvestrant (ICI 182,780) of the tongue, tonsils and other oropharynx (oropharyngeal cancer [OPC]) and a declining trend for HNC from other oral sites (oral cavity cancer [OCC]) and laryngeal cancers (LC). For instance, the population-level incidence of HPV-positive OPC in the US increased by more than 200% between 1998 (0.8 per 100 000) and 2004 (2.6 per 100 00) [2]. The declining trend for OCC and LC is consistent with the decrease in tobacco use which is a strong risk factor for these cancers [1,3,4]. Similarly, reports from HIC show increases in incidence of anal cancer [5,6]. Anal cancer incidence is estimated to be 70 per 100 000 among people living with HIV (PLHIV), but increases to 131 per 100 000 among men who have sex with men [6,7]. HPV infection is a known risk factor for OPC and anogenital cancers (AGC) including: anal, cervix, penile, vulvar and vaginal [8]. The rising OPC and anal cancer incidence may be attributable to increases in HPV prevalence associated with changes in oral and anal sex practices over time respectively [2,7]. Whilst HPV is responsible for almost all cases of cervical cancer, it is important to note that the population attributable fraction (PAF) for the other HPV-related anogenital cancers varies [9]. The PAF for OPC, anal, penile, vulvar and vaginal cancers are estimated to be 31%, 88%, 50%, 25% and 78% respectively [8]. Other important risk factors for these cancers are smoking, alcohol, older age as well as phimosis and poor hygiene for penile cancer [4,[10], [11], [12]]. HIV increases the risk of HPV infection, persistence and progression to pre-neoplastic lesions [[13], [14], [15]]. While excess mortality associated with these cancers has not been uniformly observed in regions of high HIV prevalence [16], this can be explained by premature death from more acute causes in the absence of highly effective antiretroviral therapy (ART) early on in the epidemic [14]. With expanding access to ART we may see an increase in HPV-related cancer in countries with high HIV prevalence like South Africa, as life expectancy improves and progression to invasive cancers occurs [7,17]. There are fewer data on trends of HPV-related cancers in low and middle income countries (LMIC), particularly in sub-Saharan Africa [8]. This may be attributed to poor cancer surveillance and absence of high quality cancer registries in the region [18]. It is important to understand the patterns of HNC and AGC in South Africa over the past two decades. This period covers the transition to democracy and increasing access to health care for all race groups [19]. It was also when HIV incidence began to rise prior to widespread ART access. In addition during this period, strong anti-tobacco legislation was implemented with the goal of reducing disease burden linked to tobacco use [20]. In the absence of comprehensive population based cancer registry data, we used the pathology based cancer registry data to understand the patterns and trends of HPV-related cancers. Despite the limitations, pathology-based registries can yield very useful insights, providing the results are interpreted with due care as to its inherent biases [21]. We evaluated burden of HPV-related cancers other than cervix from 1994 through to 2013. We present trends in incidence and mortality rates stratified by age groups, gender and ethnicity.
    Methods
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