Authors: Annika Antonsson et al
Although most cases of esophageal squamous cell carcinoma (ESCC) in western populations have been attributed to high levels of exposure to tobacco and alcohol, infectious agents have been postulated as possible causes, particularly human papillomavirus (HPV).
To explore this issue, we analyzed HPV DNA prevalence and HPV types together with lifestyle factors, in relation to tumor stage and survival in a low-incidence population. Archived tumor samples from a nationwide cohort of 222 ESCC patients were tested for the presence of HPV DNA by PCR; positive samples were sequenced to determine HPV type, and p16INK4a status was assessed by immunohistochemistry.
Of 222 ESCC patients, 8 tested HPV positive (prevalence, 3.6%; 95% confidence interval, 1.1-6.1%), of which 6 were HPV-16 positive and 2 were HPV-35 positive. Four of the eight HPV-positive tumors overexpressed p16INK4a. None of 55 normal esophageal tissue samples from healthy participants had any detectable HPV. Although the numbers were low, it seemed that patients with HPV-positive ESCC tumors were younger than those with HPV-negative tumors (mean age, 60.8 versus 65.3 years, P = 0.18) and had higher body mass index (BMI) throughout life (mean current BMI of 25.1 for HPV positive, 22.2 for HPV negative, P = 0.08; mean BMI at 20 years of 25.8 for HPV positive, 22.1 for HPV negative, P = 0.003). We found no difference between patients with HPV-positive and HPV-negative tumors with respect to other lifestyle factors.
Conclusions: These findings suggest a very low prevalence of HPV DNA in human ESCC.
HPV is very unlikely to be a common cause of ESCC in Australia. Cancer Epidemiol Biomarkers Prev; 19(8); 20.
1. The Australian Cancer Study: Esophageal Cancer: Investigators: David C. Whiteman, Penelope M. Webb, Adele C. Green, Nicholas K. Hayward, Peter G. Parsons, David M. Purdie. Clinical collaborators: B. Mark Smithers, David Gotley, Andrew Clouston, Ian Brown. Project Manager: Suzanne Moore. Database: Karen Harrap, Troy Sadkowski. Research Nurses: Suzanne O’Brien, Ellen Minehan, Deborah Roffe, Sue O’Keefe, Suzanne Lipshut, Gabby Connor, Hayley Berry, Frances Walker, Teresa Barnes, Janine Thomas, Linda Terry, Michael Connard, Leanne Bowes, MaryRose Malt, Jo White.
2. Study of Digestive Health: Investigators: Queensland Institute of Medical Research, Brisbane Australia: David C. Whiteman, Adele C. Green, Nicholas K. Hayward, Peter G. Parsons, Sandra J. Pavey, David M. Purdie, Penelope M. Webb; University of Queensland, Brisbane, Australia: David Gotley, B. Mark Smithers; The University of Adelaide, Adelaide, Australia: Glyn G. Jamieson; Flinders University, Adelaide, Australia: Paul Drew, David I. Watson; Envoi Pathology, Brisbane, Australia: Andrew Clouston.
3. Research Staff: Project Manager: Suzanne O’Brien; Research Scientist: Derek Nancarrow; Research nurses: Andrea McMurtrie, Linda Terry, Michael Connard, Deborah Roffe, Lorelle Smith, Marian Martin, Jeanette Mayhew, Susan Perry, Marcia Davis.
Annika Antonsson1, Derek J. Nancarrow2, Ian S. Brown3, Adele C. Green1, Paul A. Drew4, David I. Watson5, Nicholas K. Hayward2 and David C. Whiteman1 for the Australian Cancer Study1
1Genetics and Population Health Division and 2Oncogenomics, Queensland Institute of Medical Research, and 3Sullivan Nicolaides Pathology and Royal Brisbane and Women’s Hospital Brisbane, Brisbane, Queensland, Australia; 4School of Nursing and Midwifery, and 5Department of Surgery, Flinders University, Bedford Park, South Australia, Australia