Human papillomavirus (HPV) 16 antibodies at diagnosis of HPV-related oropharyngeal cancer and antibody trajectories after treatment

Abstract

Objectives Despite the fact that HPV-driven oropharyngeal cancer (HPV-OPC) has relatively low recurrence rates, intensive post-therapy monitoring remains the standard of care. Post-treatment biomarkers are needed to risk stratify HPV-OPC patients for more individualized surveillance intensity and which remain at higher recurrence risk. Materials and Methods 115 HPV-OPC patients (ascertained by p16 immunohistochemistry and/or in-situ hybridization) from a multicenter prospective case study (HOTSPOT) had blood collected at diagnosis, and 64 of these also had blood collected at post-treatment follow-up visits for up to two years. Samples were centrally tested for antibodies to the L1, E1, E2, E4, E6, and E7 proteins of HPV16. Results At diagnosis, most HPV-OPC cases were seropositive to HPV16 E6 (85%). In post therapeutic samples, HPV16 antibody level decreased slowly over time, but only 3 (of 51 cases seropositive at enrollment) dropped low enough to be classified as seronegative. At 3 years after diagnosis, cumulative risk of recurrence was 10.2% and 0% in HPV16 E6 seropositive and E6 seronegative HPV-OPC cases, respectively (p = 0.18). Risk of recurrence was increased, although not statistically significant, in those with higher HPV16 E6 antibody levels at diagnosis (per log antibody level, hazard ratio [HR] = 1.81, 95%CI = 0.47–6.92). Conclusion This study confirms the high seroprevalence of HPV oncogenic antibodies at diagnosis of HPV-OPC. HPV16 E6 antibody levels decrease after treatment, but most cases remain seropositive for up to two years. HPV16 E6 antibody levels at diagnosis did not appear to be a strong predictor of recurrence.

Human papillomavirus 16 E6 antibodies are sensitive for human papillomavirus–driven oropharyngeal cancer and are associated with recurrence

“…In many of these serum‐based studies, information regarding the HPV status of the tumors was not available, or the HPV status was assessed with non–gold‐standard methods. Thus, the sensitivity of HPV16 E6 seropositivity for detecting the subset of tumors caused by an HPV infection is unknown.…”

Antibodies against human papillomaviruses as diagnostic and prognostic biomarker in patients with neck squamous cell carcinoma from unknown primary tumor

“…HPV16 E6 antibodies were highly elevated and stable up to 13 years prior to OPSCC diagnosis . After curative treatment of HPV‐positive OPSCC, antibody levels were reported to decline . In patients with non‐HPV‐driven tumors and in healthy individuals, the prevalence of antibodies against HPV early proteins is low .…”

Prognostic value of posttreatment HPV‐specific antibodies in patients with oropharyngeal tumors

“…Decreasing levels of antibodies to viral oncoproteins HPV16 E6 and E7 have been reported by several studies, but for HPV‐derived VLPs, the decrease was less evident . Scarce studies which evaluated the dynamic of changes of HPV‐specific antibodies in patients treated for HN tumors were mostly short‐term and they reported similar observations as for patients with cervical cancer …”

“…Spector et al observed higher levels of HPV16 E6 and E7 antibody on diagnosis and the follow‐up in recurrent patients with faster clearance of E7 antibodies in patients without recurrences. However, others did not observe differences in the HPV16 E6 antibody levels on the follow‐up in those patients who recurred and who did not …”

“…The decline in the E6/E7 antibodies levels was not observed in patients with recurrent disease in the study by Koslabova et al Spector et al found significantly higher levels of HPV16 E6/E7 antibody in recurrent patients at diagnosis as well as on the follow‐up with a more frequent clearance of HPV16 E7 antibodies in patients without recurrences during follow‐up. Others did not report any differences in HPV16 E6 antibody levels in patients with and without recurrences …”