Surgical salvage improves overall survival for patients with HPV‐positive and HPV‐negative recurrent locoregional and distant metastatic oropharyngeal cancer

Abstract

Background Human papillomavirus (HPV) tumor status and surgical salvage are associated with improved prognosis for patients with recurrent oropharyngeal squamous cell carcinoma (OPSCC). Current data regarding types of surgery and the impact of surgery for distant metastatic disease are limited. Methods A retrospective analysis of patients with recurrent OPSCC from two institutions between 2000-2012 was performed. P16 immunohistochemistry and/or in situ hybridization, as clinically available, were used to determine HPV tumor status. Clinical characteristics, distribution of recurrence site and treatment modalities were compared by HPV tumor status. Overall survival was examined by Kaplan-Meier and Cox proportional hazards methods. Results The study included 108 patients with 65 locoregional and 43 distant metastatic first recurrences. The majority were HPV-positive (n=80). HPV-positive tumor status was associated with longer time to recurrence (p<0.01). Anatomic site distribution of recurrences did not differ by HPV tumor status. HPV-positive tumor status (adjusted HR [aHR] 0.23 (95%CI 0.09-0.58), p=0.002), longer time to recurrence (≥1 year; aHR 0.36 (0.18-0.74), p=0.006), and surgical salvage (aHR 0.26 (0.12-0.61), p=0.002) were independently associated with overall survival after recurrence. Surgical salvage was independently associated with improved overall survival compared to non-surgical treatment in both locoregional (aHR 0.15 (0.04-0.56), p=0.005) and distant metastatic recurrence (aHR 0.19 (0.05-0.75), p=0.018). Conclusions Surgical salvage is associated with improved overall survival for recurrent locoregional and distant metastatic OPSCC, independent of HPV tumor status. Further prospective data is needed to confirm the role of surgical salvage for distant metastases.

Serum Antibodies to HPV16 Early Proteins Warrant Investigation as Potential Biomarkers for Risk Stratification and Recurrence of HPV-Associated Oropharyngeal Cancer

“…To date, there is no method to identify the patients who will unfortunately experience disease recurrence after therapy. Indeed, HPV-positive patients at the time of recurrence retain the phenotype of HPV-positive patients; those who recur are not the HPV-positive patients with characteristics more similar to HPV-negative patients (7–9). Therefore, serology at the time to diagnosis may be a biomarker to identify patients who need more or less intense follow-up.…”

“…The presence of HPV in oropharyngeal tumors confers improved overall- and progression-free survival, relative to HPV-negative tumors (5, 6). Despite improved prognosis, up to 27% of HPV-positive patients still experience recurrence of disease, the majority of which occurs in the first two years after treatment (7–9). …”

“…However, recent data suggest that at the time of disease recurrence, HPV-positive tumor status and surgical salvage are independently associated with improved overall survival (8). Two-year overall survival is 25% greater for recurrent HPV-positive patients who undergo surgical salvage as compared to those who do not (7, 8). Therefore, if recurrent HPV-positive OPC is detected at an early stage when surgical salvage is possible, patients may have a significant improvement in overall survival, although whether improved lead time afforded by any potential biomarker would change the outcome is unknown.…”

The Presence of HPV DNA in Neck Lymph Node Metastasis Correlates with Improved Overall Survival of Patients with Oropharyngeal Cancer Undergoing Surgical Treatment

“…However, the salvage rate among patients with HPV-positive tumours was higher than that among patients with HPV-negative tumours. Guo et al [22] reported that surgical salvage was associated with improved OS for 65 cases of recurrent locoregional OPSCC and 43 cases of distant metastatic OPSCC; this relationship existed independently of tumour HPV status. This result is consistent with a study reported by Patel et al [23] in which HPV status was not associated with either OS or relapse-free survival in 34 patients who underwent salvage surgery for locally recurrent or persistent OPSCC after chemoradiotherapy.…”

Post-Treatment Circulating Free HPV DNA As a Marker of Treatment Outcome in Patients with HPV-Related Propharyngeal Cancer After Radio(chemo)therapy

“…The concentration of the total cfDNA was between 0.118 ng/µl and 1.130 ng/µl. The concentration of the total cfDNA did not influence the cfHPV DNA detection as we presented before [11][12][13][14][15][16]. For HPV16 detection primers and probe sequence were designed for E6/7 region.…”