In 1976, German virologist Harald zur Hausen, MD, DSc, proposed that human papillomavirus (HPV) causes cervical cancer, countering the widely held belief that herpes simplex virus caused the cancer. Seven years later, he proved the theory, showing that HPV genes are incorporated into cervical cancer cells. Subsequently, HPV has been shown to cause anal, penile, vulvar, vaginal, and oropharyngeal cancers, in addition to cervical cancer.
Some patients with esophageal cancer test positive for HPV, which has been linked to other gastrointestinal cancers, notably anal cancer, but also gastric and colorectal cancer. The authors of a recent review cited estimates of HPV positivity in esophageal adenocarcinoma (EAC), the predominant histologic subtype in the U.S., ranging from 13% to 35%.
Estimates vary broadly by geography. For example, a systematic review of 15 mostly small studies, published almost a decade ago, showed HPV positivity in up to 93% of EAC specimens. A U.S. study included in the review showed an HPV-positive rate of 16.8%.
Much of the contemporary data on HPV and esophageal cancer come from Asia, which has a much higher incidence of esophageal cancer as compared with the U.S. The American Cancer Society estimates that 22,530 esophageal cancers will be diagnosed in the U.S. in 2026, whereas the global incidence exceeds 500,000 cases annually.
