The Relationship between Human Papillomavirus and Oesophageal Squamous Cell Carcinoma in China—A Review of the Evidence

Abstract

Background: China has one of the highest incidence rates of oesophageal cancer in the world. The role of human papillomavirus (HPV) has been extensively researched in oesophageal squamous cell carcinoma (OSCC) with indeterminate results. The majority of these studies have been conducted in the Chinese population. Evidence for a definitive HPV-OSCC association could potentially support prophylactic vaccination in target populations, highlighting the need for ongoing investigation. The aim of this review is to summarise the findings of HPV DNA in OSCC tissue in Chinese subjects, with a view to informing further research in this area. Methods: A systematic literature search of the Chinese National Knowledge Infrastructure (CNKI) database, Medline, Embase and PubMed was conducted for all studies in English and Chinese language, examining OSCC tissue for HPV DNA in China. Reference lists of retrieved articles were reviewed and hand searches of relevant, key journals were conducted, to source articles which were not electronically indexed. Sixty-four studies met our selection criteria. Data from case-control and cross-sectional studies were analysed separately for any HPV-OSCC association, using the Epi Info ™ 3.5.3 software program. Results: From all studies conducted in the Chinese population, 2166/5953 (36%) of all OSCC tissue and 478/1684 (28%) of healthy control tissue, tested positive for HPV. We found that 11/16 case-control and cross-sectional studies had a statistically significant crude odds ratio, which supported a potential HPV-OSCC association. The largest study, carried out in the high incidence County of Anyang in Henan Province, reported 207/265 (78%) OSCC tissues testing positive for HPV DNA against 203/357 (57%) controls and had an unadjusted odds ratio of 2.71 (p-value < 0.0001). Conclusion: A rigorous meta-analysis would improve interpretation of the data and a well-designed large-scale case-control study is warranted. If a link is found between HPV and OSCC, prophylactic HPV vaccines could be of significant benefit in China.

Evidence for the aetiology of human papillomavirus in oesophageal squamous cell carcinoma in the Chinese population: a meta-analysis

“… *Some of the data included in the table have been described in one of our previous publications. 10 †All ORs in this table are unadjusted and have been calculated using the Epi Info programme, except for two studies (Cao et al and Gao et al ), where the authors of the respective articles provided calculated adjusted ORs. ‡One paper (Li et al ) has an OR deemed to be incalculable as a result of one or more of the four components for OR calculation being a zero value.…”

“… 23 Despite the high overall rate of HPV detection in OSCC in China, different studies have found a geographical variation in the rates of HPV in OSCC, possibly a real variation, but possibly in part reflecting the different detection methods used. 19 10 However, a recent study found no significant impact of the different detection methods on the detection rates of HPV. 23 This complexity and the high disease burden of OSCC in China highlight the need to better understand the relationship of HPV to OSCC in China.…”

“… 8 9 Even within China, however, there are large regional variations in the incidence of OSCC, thought to be due to variations in cofactors such as diet and environmental risk factors. 4 10–12 Established risk factors for OSCC include smoking and alcohol, but a range of other risk factors have also been identified. 13–19 Human papillomavirus (HPV) as a risk factor for OSCC was first suggested in 1982, 20 with detection of HPV DNA in OSCC tissue ranging from 15% to 80% globally.…”

Oesophageal squamous cell carcinoma (ESCC): Advances through omics technologies, towards ESCC salivaomics

“…The increased risk factor in this case as indicated by Cheng and Day (22) may come as a consequence from a direct contact of the potential carcinogen with the epithelium, some existing transport facilitating mechanism, or derived from compounds that increase the cell turnover in the epithelial cells. Albeit yet a controversial topic, there have been also studies trying to correlate the occurrence of HPV infections and ESCC, though results showed an elevated degree of variation that did not yield a clear association between the viral infection and the development of the disease (24)(25)(26).…”