High-Risk Human Papillomavirus in Esophageal Squamous Cell Carcinoma

Antonsson, Annika; Nancarrow, Derek J.; Brown, Ian; Green, Adèle C.; Drew, Paul A.; Watson, David I.; Hayward, Nicholas K.; Whiteman, David C.

doi:10.1158/1055-9965.epi-10-0033

Cited by 82 publications

(81 citation statements)

References 45 publications

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“…Although infections with Human Papillomavirus or Helicobacter pylori have been suggested previously as factors possibly accounting for some cases of ESCC, recent analyses from this study population provide no support for such mechanisms. [19,20] Only three sex-specific analyses for ESCC have been reported previously in the literature, and our estimates of PAF are reasonably similar to those. In an Italian casecontrol study, Negri and colleagues reported PAFs for smoking of 32% in women and 61% in men, and PAFs for high alcohol consumption of 10% in women and 39% in men; the overall PAF for the joint effect of the two factors was 40% in women and 84% in men [7].…”

Section: Discussionsupporting

confidence: 86%

Sex differences in the proportion of esophageal squamous cell carcinoma cases attributable to tobacco smoking and alcohol consumption

Pandeya

Olsen

Whiteman

2013

Cancer Epidemiology

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Objective: Alcohol and tobacco are the two major established environmental factors associated with squamous cell carcinoma of the esophagus (ESCC). However, the prevalence of these exposures differs substantially between men and women. Moreover, the prevalence of smoking has declined in recent years, whereas per capita consumption of alcohol has remained steady in both sexes. Quantifying the burden of ESCC attributable to these causal factors is necessary to inform potential preventive strategies. Methods: We estimated the population attributable fraction (PAF) of ESCC due to smoking and alcohol, using data from an Australian population based case-control study (305 ESCC cases, 1554 controls). Results: Estimated PAF for ESCC were 49% (95%CI: 38-60) and 32% (95%CI: 25-40) due to smoking and heavy alcohol consumption respectively. More than 75% of the ESCC burden in men could be attributed to smokers with heavy alcohol consumption. The highest burden was among ≥30 pack years smokers who also consumed alcohol heavily (>17 drinks/week); this differed significantly between men (PAF 36%, 95%CI 29-44) and women (PAF 5%, 95%CI 2-10). Among women only, low intakes of fruit and vegetables accounted for about 9% of the ESCC burden. Conclusion: The burden of ESCC attributable to smoking combined with heavy alcohol consumption is remarkably high in men. In women, the burden of ESCC due to these factors is lower, and poor nutrition may also play a role.

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Section: Discussionsupporting

confidence: 86%

Sex differences in the proportion of esophageal squamous cell carcinoma cases attributable to tobacco smoking and alcohol consumption

Pandeya

Olsen

Whiteman

2013

Cancer Epidemiology

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“…We read with interest the recent article excluding human papillomavirus (HPV) as a significant contributor in esophageal squamous cell cancers (ESCC), at least in Australia (1). This is in contradistinction to oropharyngeal cancers (OPC) where there is compelling epidemiologic and molecular evidence indicating HPV as the etiology of a subset of cases.…”

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confidence: 99%

“…In a recent study of 302 cases, the incidence of HPV-related OPCs We question whether the HPV rates have been fully determined in this ESCC series, due to potential methodologic problems. The authors used internal control primers which amplify a 110-bp region of the b-globin gene (1). This contrasted with the 150-bp HPV L1 amplicon generated with GP5 þ /6 þ primers.…”

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confidence: 99%

High-Risk Human Papillomavirus in Esophageal Squamous Cell Carcinoma—Letter

Garland

Tabrizi

Segelov

et al. 2011

Cancer Epidemiology, Biomarkers &Amp; Prevention

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We read with interest the recent article excluding human papillomavirus (HPV) as a significant contributor in esophageal squamous cell cancers (ESCC), at least in Australia (1). This is in contradistinction to oropharyngeal cancers (OPC) where there is compelling epidemiologic and molecular evidence indicating HPV as the etiology of a subset of cases. Within Australia, there is a changing epidemiology of OPCs. In a recent study of 302 cases, the incidence of HPV-related OPCs increased from 19% in 1987OPCs increased from 19% in to 1990OPCs increased from 19% in , 47% in 2001OPCs increased from 19% in to 2005OPCs increased from 19% in , to 60% in 2005OPCs increased from 19% in to 2006. Reports worldwide vary considerably in finding HPV in ESCC: with rates up to 81% (3). The clinical implications of excluding HPV as a major contributor to ESCC are important, particularly as HPV-related cancers have better prognosis and chemoradiation responses than their non-HPV counterparts.We question whether the HPV rates have been fully determined in this ESCC series, due to potential methodologic problems. The authors used internal control primers which amplify a 110-bp region of the b-globin gene (1). This contrasted with the 150-bp HPV L1 amplicon generated with GP5 þ /6 þ primers. It would be standard practice to use an internal control of longer or equal length to the HPV amplicon, to ensure DNA below 150 bp has not degraded (4). Also, there are several aspects of the described PCR method which could contribute to lower assay sensitivity. Firstly, the authors modified the MgCl 2 concentration to 2 mmol/L from the original assay description of 3.5 mmol/L. This would increase PCR stringency, but reduce sensitivity. The assay sensitivity in detecting HPV in tissue should be stated.Secondly, the amplicons were analyzed by gel electrophoresis, a less sensitive method than using HPV-specific probes. If original paraffin-embedded tissue blocks were small, faint amplicon bands could be missed: although would not explain so many negatives. (This would be further exacerbated if there were DNA degradation). In addition, if there were HPV integration there could be interruption of the site being amplified.It is standard when looking for HPV DNA in tissue that the sample used for PCR also has samples collected either side, to be rechecked histologically for tumor. This ensures that the sample is adequate for HPV PCR (5). We note that 22 (10%) of the total samples analyzed were from slide sections: the remainder from tissue blocks. Amplification from slide sections is less sensitive than from tissue. This is of relevance given that none of the 22 slides examined were HPV positive. Disclosure of Potential Conflicts of InterestS. M. Garland, advisory board for cervical cancer vaccines, honoraria for speakers bureau, and through her institution received monies for research on cervical cancer vaccine phase 3 trials.No other potential conflicts of interest were disclosed.Received August 29, 2010; revised September 21, 2010; ac...

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“…We thank Garland and colleagues for their interest in our study (1) and for raising the important issue of the sensitivity of the procedures we used to detect human papillomavirus (HPV) in esophageal squamous cell carcinoma (ESCC). More precisely, they have expressed concerns that our ability to detect HPV in ESCC tumor samples may have been compromised by degradation of DNA in formalin-fixed paraffin embedded (FFPE) tissue samples; modified MgCl 2 concentration; use of electrophoresis and sequencing instead of HPV type-specific probes; or potentially suboptimal histologic assessment of tumor samples.…”

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confidence: 99%