HPV Status Impacts Therapy Decisions for Barrett HGD and Esophageal Cancer

Results from a case-control study suggest that therapy for patients with Barrett high-grade dysplasia (HGD) and esophageal adenocarcinoma may be personalized based on their human papillomavirus (HPV) status (JAMA Netw Open. 2020;3[2]:e1921189).

Although high-risk HPV has been tied to favorable outcomes in patients with Barrett HGD and esophageal adenocarcinoma, the predictive significance of other HPV-related biomarkers (ie, retinoblastoma protein [pRb], cyclin D1 [CD1], minichromosome maintenance protein [MCM2], and Ki-67) remains unknown.

Thus, Shanmugarajah Rajendra, MBBCh, MSc, MD, FRACP, Gastro-Intestinal Viral Oncology Group, Ingham Institute for Applied Medical Research, Liverpool, Sydney, New South Wales, Australia, and colleagues conducted a retrospective study of the link between HPV-related biomarkers and survival in adults with Barrett HGD and esophageal adenocarcinoma.

Between December 1, 2002, and November 28, 2017, a total of 142 patients (mean age, 66.0 years) were included in the study, including 37 who were HPV-positive and 105 were HPV-negative. Dr Rajendra et al hypothesized that the HPV-related cell cycle markers (pRb, CD1, and Ki-67) and viral surrogate marker (MCM2) may be indicative of favorable prognosis in these patients.

“Pretreatment biopsies were used for HPV DNA determination via polymerase chain reaction and immunohistochemistry for the HPV-related biomarkers,” the investigators explained.

Study data were analyzed from September 9, 2011, to November 28, 2017, with the main outcome measures being disease-free survival (DFS) and overall survival (OS).

Ultimately, pRb, CD1, Ki-67, and MCM2 yielded no association with DFS, and only low expression of CD1 was associated with a favorable prognosis of OS (hazard ratio [HR], 0.53; 95% CI, 0.30-0.95; adjusted P = .03).

When stratified by HPV status, all biomarkers displayed significant ties to survival. Compared with patients who had HPV-negative, high-expression Rb tumors, those with HPV-positive, low-expression pRb esophageal tumors had a significantly improved DFS (HR, 0.33; 95% CI, 0.12-0.93; adjusted P = .04).

Correspondingly, patients with HPV-positive tumors and low expression of CD1 had a significantly favorable DFS (HR, 0.26; 95% CI, 0.09-0.76; adjusted P = .01), as did those with HPV-positive tumors and high expression of MCM2 (HR, 0.27; 95% CI, 0.09-0.78; adjusted P = .02). Notably, when it came to OS, HPV was significantly tied only to low expression of CD1 (HR, 0.38; 95% CI, 0.15-0.94; adjusted P = .04).

“[HPV] positivity in combination with pRb, CD1, MCM2, and Ki-67 was associated with a survival benefit in esophageal tumors. These findings suggest the possibility of personalization of therapy for Barrett HGD and EAC based on viral status,” Dr Rajendra and co-investigators concluded.—Hina Porcelli