An investigation into the role of human papillomavirus in oesophageal squamous cell carcinoma

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Copyright: Liyanage, Surabhi
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Abstract
Background: Oesophageal cancer has a complex, multifactorial aetiology, which may account for its wide geographical variation in incidence. The potential role of human papillomaviruses (HPV) in the aetiology of oesophageal squamous cell carcinoma (OSCC) has been widely studied, with inconclusive results. China has contributed the largest number of studies to this topic of research and has one of the highest rates of OSCC incidence in the world. Since the recent introduction of prophylactic HPV vaccines, it has become more important to determine whether an HPV-OSCC link exists. Case-control methodology is the most suitable study design to answer this research question. The question of HPV and OSCC has been unanswered because most studies conducted have had poor or inappropriate study design, and those few which had a case-control design were small scale, and unable to answer the question as individual studies. The aim is to conduct meta-analyses using global and Chinese data to provide a means of using these few, small-scale studies to address the question more robustly. In addition an Australian case-control study will be performed to evaluate any potential association of HPV with OSCC in a low-incidence country. Methods: A review of the current evidence was conducted through searches of the literature from MEDLINE, EMBASE, PUBMED and CNKI (Chinese language database), including hand searches of key journals, with a review of the global epidemiology and then a specific review focused on China. A case-control study in the Australian population was done. The results of this were pooled with the only other Australian case control study. A meta-analysis of all case-control studies conducted globally in English language was then carried out. This was followed by a meta-analysis of Chinese studies, including all studies identified in the Chinese language literature. The global meta-analysis identified 21 case-controls including 1223 cases and 1415 controls. The Chinese meta-analysis included collective analysis of 1177 cases and 1648 controls from the 15 case-control studies. The random effects method was used to pool the odds ratios. Results: There were 139 studies of HPV and OSCC in the literature, but of these only 23 were case control studies and therefore suitably designed to answer the question. The remainder of the studies were case series. The Australian case-control study identified HPV 16 DNA in 1/99 case specimens (rate of 1010/100,000, 95%CI 30 to 5500); control specimens were negative for HPV. A pooled analysis of data from this study with a similar case control study shows 9/322 cases and 0/154 controls positive for HPV. An estimated odds ratio for HPV being a risk factor for OSCC was 4.9 (95% CI 0.6-103, p=0.1). Of all OSCC specimens, 35% (426/1223) included in the global meta-analysis were HPV positive, and 27% (380/1415) of controls were positive. The pooled OR for an HPV-OSCC association was 3.04 (95%CI 2.20 to 4.20). The Chinese meta-analysis also revealed a strong association between HPV and OSCC (OR 3.69, 95%CI 2.74 to 4.96). Conclusion: In Australia, the major risk factors for OSCC appear to be smoking and alcohol, but HPV is not excluded as a risk factor, and a pooled analysis with the only other Australian case-control study is suggestive of an association. The results of the meta-analyses, which adds statistical power to answering this question, suggest that HPV increases the risk of OSCC three-fold. These studies provide the strongest evidence to date internationally of an HPV-OSCC association. As prophylactic vaccination could be of public health benefit in the reduction of OSCC incidence rates in countries with high OSCC incidence, these data should be considered by IARC (International Agency for Research on Cancer).
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Author(s)
Liyanage, Surabhi
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MacIntyre, Raina
Fitzpatrick, Holly
Rahman, Bayzidur
Newall, Anthony
Crowe, Philip
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Publication Year
2014
Resource Type
Thesis
Degree Type
PhD Doctorate
UNSW Faculty
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