Discussion
HNCs constitute a major public health concern worldwide. There has been a significant increase in the global incidence of HNC, which is increasing sharply in developing countries (1). Studies from South America and West Africa have shown a similar burden of disease (7-9). Limited data onthe epidemiological trends of HNC in Southern Africa exist. The aim of the current study was to describe the profile of HNC at a major referral public hospital (TBH, Western Cape, South Africa) in Southern Africa. This information may help to develop effective education and research efforts by local and international non-governmental agencies to help reduce the mortalities and morbidities associated with HNC.
854 patients were diagnosed with HNC between 2015 and 2017, representing 12.7% of all patients seen at the Radiation Oncology Department at TBH during this period. The median age in this cohort was 58 years, with most patients being between the ages of 51 and 70 years, similar to the global age trend observed for tobacco-associated HNC(5). Over 70% of patients were males, consistent with the existing reports that men are two to three times more likely to develop HNC (5). The male: female ratio was 2.4:1; and globally this ratio varies between 2:1 to 4:1. (10)
The most predominate histologic type was SCC, which accounted for 791 (92.6%) of all HNC cases. Smoking was a risk factor in 737 of the subjects (86.3%), and alcohol in 634 (74.2%). Both smoking and alcohol were co-risk factors 72.6% (n=620) of the patients. Tobacco smoking and alcohol consumption are well-established major risk factors for HNC and a synergistic effect of these two factors has been consistently reported(11).
HR-HPV is an established risk factor for the development of Oropharyngeal Squamous Cell Carcinoma (OPSCC). There is significant geographic heterogeneity in the prevalence of HPV-positive OPSCC.
Of 167 patients with oropharyngeal primaries, 9.58% (n=16) had p16-positive SCC.46.70% (n=78) were p16-negative and the p16 status was unknown in 43.7% (n=73). Only 3 of the p16 positive OPSCC were HPV-DNA positive, suggesting that p16 appears to have a low positive predictive value in our setting, and may not be used as a standalone HPV test or a surrogate marker for HR-HPV infection. Eleven of the patients with p16-positive tumours had both smoking and alcohol as risk factors, and it appears that mechanismsother than HR-HPV infection may be involved (e.g. Rb mutation) in p16 overexpression.
A large number of oropharyngeal primaries (43.7%) had unknown HPV status, due to the fact that p16 became a routine test for oropharyngeal primaries at this hospital in recent years. Thus, we are unable to draw conclusions about the overall prevalence of HPV-positive OPSCC at TBH during the study period. However, given the very low incidence of true HPV-positive cases in the cohort of OPSCC cases with known p16 status (3/94=3.2%), it may be speculated that HR-HPV exposure is possibly not a major risk factor for the development of OPSCC at this centre.
Indeed, the increasing incidence of HNC in Southern Africa is mostly due to increasing smoking and drinking habits, and that preventative strategies/campaigns should primarily target tobacco and alcohol industries. Nevertheless, many countries in Africa are undergoing economic modernization, resulting in major changes in lifestyle, diet and sexual behaviour and in coming years we may observe an increasing incidence of HPV-positive OPSCC.
Fifty-six (9%) patients were HIV positive, 721 (84%) were HIV negative and 77 (7%) had unknown HIV status. The HIV prevalence in the Western Cape was 12.6% in 2017(12). The South African National HIV Prevalence, Incidence and Behaviour Survey in 2012 reported an HIV prevalence of 7.6% in individuals over 50 years of age(12). The prevalence of HIV infection in our cohort of patients with the median age of 58 years, is similar tothe nationwide prevalence of 9% in patients over 50 years of age. It appears that HIV infection plays a minor role in the development of HNC in South Africa. The exact mechanism of HIV promoted carcinogenesis is not known(13).
According to the 2011 South African census, low-income households are classified as those with a combined annual household income of below R19200 ($1280). In this study, 56% of the patients fall into the low-income category. Studies have shown an increased risk of HNC in individuals of lower socioeconomic status, even after controlling for other risk factors such as smoking and alcohol consumption(14,15). We can deduct from the latter that comprehensive HNC control programmes should also address the social inequalities and the high unemployment rate in Southern African countries.
The most common anatomical site in this study was the oral cavity (320, 37%), followed by the larynx (188, 21.73%) and the oropharynx (167, 19.31%). The most common sub-site was the anterior tongue, accounting for 15.84% (137) of the cases, followed by supraglottis 11.33% (98) and the glottis 10.40% (90), in descending order of frequency. The Surveillance, Epidemiology, and End Results [SEER] Programme reports that the commonest site for HNC is the oral tongue followed by the larynx (16).
Field cancerization describes the presence of premalignant fields surrounding the primary tumour and has been related to the high rate of local recurrence in HNC as well as the development of synchronous primaries (17). Synchronous cancer is defined as two or more neoplasms identified simultaneously in the same patient. It is estimated that 1 to 6% of the patients diagnosed with SCC of head and neck will have a synchronous primary in the head and neck region (18). In this study eleven patients (1.3%) presented with a synchronous primary in the head and neck region.
According to the Surveillance, Epidemiology, and End Results (SEER) database, in the United States 42-62% of patients with HNC presented with locally advanced disease and 16-27% with distant metastases(2). An epidemiological review of head and neck patients at a university hospital in Brazil reported that 47.8% of patients had T3/T4 disease and 31.9% had node positive disease(7). In the current study, a significant number of patients presented with locally advanced disease (53.87%, n=466), consistent with the data from the SEER database. The incidence of distant metastases was 6.21%, which is lower than that of patients presenting in the United States.
The treatment intent and modality offered to patients depends on multiple factors, i.e. stage at presentation, performance status, co-morbidities, social circumstances as well as patient wishes. In our patient group, 449 (52.6%) patients had treatment with radical intent and 405 (47.4%) with palliative intent. The majority of patients in the radical intent group had surgery (72.4%) and approximately the same proportion of patients received radiotherapy as part of their treatment. 226 patients (50.3%) received combined modality, including surgery, chemotherapy and radiotherapy.
Of the patients that received palliative intent, 76.5% received radiotherapy and 21.5% were not fit for any treatment and received medical palliation and best supportive care. Just less than half of the patients were for palliative intent; this could be due to the late stage at presentation. The latter could be attributed to poor socio-economic status, lack of knowledge and understanding, problems accessing health services, cultural and religious beliefs, and possible other unknown factors i.e. genetic factors in this patient population.