An Australian study is the first to demonstrate better survival in patients with high-grade Barrett dysplasia or oesophageal cancer associated with human papillomavirus (HPV) than patients with dysplasia or malignancy who do not have the viral infection.
The findings, from a retrospective case-control study of 37 HPV-positive and 102 HPV-negative patients, open up the possibility of de-escalating treatment in patients whose disease appears to be related to HPV.
The study found disease-free survival in HPV-associated oesophageal cancer was 40.3 months compared to 24.1 months in the HPV-negative patients and overall survival was 43.7 months compared to 29.8 months.
HPV DNA positivity in the oesophageal lesion, transcriptional HPV positivity, and markers of activity such as E6 and E7 mRNA were all associated with improved disease-free survival (HR = 0.36-0.39).
Rates of recurrence or progression (24.3 v 58.1%), disease metastases (8.1 v 27.6%) and deaths due to esophageal cancer (13.5 v 36.2%) were all lower in HPV-positive patients.
The researchers said their findings were consistent with similar work in head and neck squamous cell carcinomas (HNSCC).
“Human papillomavirus-positive HNSCCs have improved survival and lower rates of local and regional recurrence compared with HPV-negative head and neck cancers.”
“The results of this study are consistent with our previous work that demonstrated HPV-positive and HPV-negative EAC are distinct diseases just as in HNSCC.”
The association of HPV status with overall survival failed to reach statistical significance by the log-rank test, possibly related to the relatively small size of the study and the multiple variables.
The researchers said the findings should be confirmed in larger cohorts and in those with more advanced disease, given almost 90% of the study group were N stage 0-1.
Professor Shan Rajendra, director of the Gastro-Intestinal Viral Oncology Group at the Ingham Institute for Applied Medical Research, told the limbic that molecularly distinct entities of esophageal cancer had important clinical implications.
“Essentially, the HPV mechanism is via wild type p53 and the retinoblastoma protein pathway. It basically circumvents the classical p53 mutation pathway and by circumventing that pathway, the HPV-positive group survive longer.”
Treatment de-escalation strategies in the HPV-positive patients might be possible and entail reducing radiation or chemotherapy doses or avoiding radiation therapy altogether, he said.
“Do we really neoadjuvant therapy prior to surgery? Could we get away with endoscopic mucosal resection without having to go to surgery? Do we need to subject these patients to a life-threatening oesophagectomy – a more serious surgery than a cardiac bypass – where the mortality rate can be high?”
“Those are the sort of questions that we should be looking at in the near future and I think that some of that is being looked at already in the head and neck arena.”
He added that one of more exciting future possibilities was the use of a therapeutic vaccine targeting HPV E6 and E7 as neoadjuvant therapy instead of radiation therapy or chemotherapy.