From the Journals

HPV positivity associated with good esophageal adenocarcinoma outcomes

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“Impressive,” but a prospective trial is called for

The study by Rajendra et al highlights the potential role of human papillomavirus (HPV) status in the prognosis of esophageal adenocarcinoma (EAC). However, the use of HPV as a predictive marker for treatment remains unproven, and many questions abound. Important considerations for studies of de-escalation of treatment in HPV-positive EAC include how best to select patients for less intensive treatment: Should trials be restricted to nonsmoking patients with better prognosis pathology characteristics, including lower T stage and lack of lymph node involvement? What is the best method to assess HPV status in a cost-effective and easily available assay for broad international use? Should there be a de-escalation of chemotherapy, radiation, or both? Is there potentially a role for de-escalation of surgery? Are these trials that patients would consider participation in given the lethality of these cancers?

Finally, the presence of a vaccine for HPV may affect the incidence of cervical, oropharyngeal, and other cancers. If HPV is an important risk factor for EAC, we may see a reduction in the rates of this highly lethal cancer over time. These benefits may take some time to bear out and are highly dependent on vaccination rates. Nonetheless, primary prevention of HPV infection may result in a significant reduction in the global burden of this disease. In the meantime, larger-scale studies of the role of HPV in the pathogenesis of EAC are warranted, particularly before moving toward trials of less intensive therapy. While the results of this small cohort study are impressive, they are preliminary, and the study requires confirmation in a larger, prospective trial.

Sukhbinder Dhesy-Thind, MD, FRCPC is from McMaster University, Hamilton, Ontario. Her remarks are excerpted from an editorial accompanying the study. She reported personal fees from Teva Canada Innovation and Novartis Pharmaceuticals Canada outside the submitted work.



Patients with Barrett high-grade dysplasia or esophageal adenocarcinoma who are positive for human papillomavirus (HPV) infection have significantly better outcomes than patients with the same diseases who are negative for HPV, investigators report.

Among patients with Barrett high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC), mean disease-free survival (DFS) was 40.3 months for HPV-positive patients, compared with 24.1 months for HPV-negative patients (P = .003). Mean overall survival was also significantly better in HPV-positive patients, at 43.7 months versus 29.8 months (P =.009) respectively, reported Shanmugarajah Rajendra, MD, from Bankstown-Lincombe Hospital in Sydney and colleagues.

“If these findings of a favorable prognosis of HPV-positive HGD and EAC are confirmed in larger cohorts with more advanced disease, it presents an opportunity for treatment de-escalation in the hope of reducing toxic effects without deleteriously affecting survival,” they wrote in JAMA Network Open.

The findings support those of earlier studies suggesting that HPV infection is associated with better prognosis among patients with other cancers of the head and neck. For example, a retrospective analysis of data from two clinical trials reported in 2014 found that, 2 years after a diagnosis of recurrent oropharyngeal cancer, 54.6% of HPV-positive patients were alive, compared with 27.6% of HPV-negative patients (P less than .001).

To determine whether there was a similar association between HPV infection and better prognosis of Barrett HGD or EAC, Dr. Rajendra and associates conducted a retrospective case-control study of 142 patients with HGD or EAC treated at secondary or tertiary referral centers in Australia. The patients, all of whom were white, included 126 men. The mean age was 66 years, and in all, 37 patients were positive for HPV.

As noted before, both DFS and overall survival were significantly better for HPV-infected patients, with mean differences of 16.2 months and 13.9 months, respectively. HPV-positive patients also had lower rates of progression or recurrence (24.3% vs. 58.1%; P less than .001), distant metastases (8.1% vs. 27.6%; P = .02), and death from EAC (13.5% vs. 36.2%; P = .02).

In multivariate analysis, superior DFS was associated with HPV positivity, (hazard ratio, 0.39; P = .02), biologically active virus (HR, 0.36; P = .02), E6 and E7 messenger RNA (HR, 0.36; P = .04), and with high p16 expression (HR, 0.49; P = .02).

The study was supported by the South Western Sydney Clinical School; the University of New South Wales, Sydney; and the Oesophageal Cancer Research Fund. Dr. Rajendra reported grants from the University of New South Wales and the Oesophageal Cancer Research Fund during the conduct of the study. No other disclosures were reported.

SOURCE: Rajendra S et al. JAMA Network Open. 2018 Aug 3. doi:10.1001/jamanetworkopen.2018.1054.

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