Association of Biomarkers for Human Papillomavirus With Survival Among Adults With Barrett High-grade Dysplasia and Esophageal Adenocarcinoma

Abstract

IMPORTANCE The presence of high-risk human papillomavirus (HPV) has been associated with a favorable outcome in Barrett high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). Nevertheless, the prognostic significance of other HPV-related biomarkers (ie, retinoblastoma protein [pRb], cyclin D1 [CD1], minichromosome maintenance protein [MCM2] and Ki-67) is unknown. OBJECTIVE To examine the association between HPV-related biomarkers and survival in adult patients with Barrett HGD and EAC. DESIGN, SETTING, AND PARTICIPANTS This retrospective case-control study examined the hypothesis that the HPV-related cell cycle markers (pRb, CD1, and Ki-67) and the viral surrogate marker (MCM2) may be associated with a favorable prognosis in Barrett HGD and EAC. Pretreatment biopsies were used for HPV DNA determination via polymerase chain reaction and immunohistochemistry for the HPV-related biomarkers. Recruitment of patients occurred in secondary and tertiary referral centers, with 151 patients assessed for eligibility. The study period was

Human papillomavirus infection in esophageal squamous cell carcinoma and esophageal adenocarcinoma: a concise review

“…None of the biomarkers tested independently had any association with DFS; pRb, CD1, MCM2, and Ki-67 stratified by HPV status were associated with a survival benefit in esophageal tumors. 67 These findings suggest the possibility of personalization of therapy for Barrett's high-grade dysplasia and EAC based on viral status. Confirmation of these findings by other investigators in larger cohorts with more advanced disease could present an opportunity for treatment de-escalation in the hope of reducing toxic effects without deleteriously affecting survival.…”

“…These test results should be sufficiently accurate to identify patients for HPV clinical trial recruitment and to inform prognosis. 67,70 Methodology varies considerably between studies, 4,5 indicating investigator bias. Moreover, variation involves both design and detection targets, which include HPV DNA, HPV RNA, E6/E7 oncoprotein mRNA transcripts or immunohistochemistry (IHC), and cellular proteins, for example, p16 IHC.…”

“…Antibodies against HPV proteins, namely, HPV16 L1 and E6 and E7, as well as IgG against HPV16/18 capsids, are unsuitable as they have produced mixed results in a number of studies involving EAC and ESCC. 48,67,[71][72][73][74][75] A highly accurate, relatively easily undertaken, and cost-effective HPV testing method would be ideal. The test should detect the presence of HPV and evidence for transcriptional (biological) activity.…”

“…Only low cyclin D1 levels were associated with a favorable prognosis for OS. None of the biomarkers tested independently had any association with DFS; pRb, CD1, MCM2, and Ki‐67 stratified by HPV status were associated with a survival benefit in esophageal tumors 67 . These findings suggest the possibility of personalization of therapy for Barrett's high‐grade dysplasia and EAC based on viral status.…”

“…To move forward in HPV research into esophageal cancers, it is important to first standardize HPV testing of clinical samples using tests that can identify individuals with biologically active virus‐driven esophageal lesions. These test results should be sufficiently accurate to identify patients for HPV clinical trial recruitment and to inform prognosis 67,70 . Methodology varies considerably between studies, 4,5 indicating investigator bias.…”