Prognostic significance of HPV status in the re-irradiation of recurrent and second primary cancers of the head and neck

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Abstract

Purpose

To evaluate the prognostic significance of human papillomavirus (HPV) status among patients treated by salvage radiation therapy for local-regional recurrences and second primary cancers of the head and neck arising in a previously irradiated field.

Methods and materials

The medical records of 54 consecutive patients who underwent re-irradiation for squamous cell carcinoma of the head and neck occurring in a previously irradiated field were reviewed. Only patients with biopsy-proven evidence of recurrent disease that had previously been treated with doses of radiation therapy of at least 60 Gy were included. Determination of HPV status at the time of recurrence was performed by p16 immunohistochemistry. The median age at re-irradiation was 58.5 years (range, 27.9 to 81.5 years). Thirty patients (55.5%) were lifelong never-smokers. The Kaplan Meier method was used to calculate overall survival, progression-free survival, and local-regional control, and distant metastasis-free survival with comparisons between groups performed using the log-rank test.

Results

HPV status among tumors that were re-irradiated was as follows: 16 positive (29.7%); 7 negative (12.9%); 31 unknown (57.4%). The median overall survival in the entire cohort was 11.7 months (range, 8 to 27 months), with the 1-year and 2-year estimates of overall survival being 47.2% and 38.4%, respectively. A statistical trend was identified favoring patients with HPV-positive cancers with respect to the endpoints of overall survival (p = 0.06) and progression-free survival (p = 0.08) after re-irradiation when compared to the HPV-negative/unknown population. There was no significant difference in distant control between the two cohorts (p = 0.40).

Conclusions

The favorable prognostic significance of HPV seemingly extends to patients treated by re-irradiation suggesting that this biomarker may be useful in risk stratification in this setting.

Introduction

The incidence of head and neck squamous cell carcinoma (HNSCC) attributed to human papillomavirus (HPV) has risen over the last decade [1]. Although numerous studies have convincingly demonstrated that patients with HPV-positive HNSCC have a more favorable prognosis with at least half the risk of death compared to their counterparts with HPV-negative HNSCC, a significant proportion of the former group nevertheless experience disease progression [[2], [3], [4]]. For patients who develop isolated local-regional failures after initial therapy for HPV-positive HNSCC, treatment options have generally included salvage surgery, re-irradiation, chemotherapy, and/or a combination of each of the above [5]. While data from a recently published subset analysis of two prospective trials conducted by the Radiation Therapy Oncology Group (RTOG) showed that HPV status remains a strong prognostic factor in the recurrent setting (with a 2-year overall survival rate of 55% in HPV-positive patients compared to 28% in the HPV-negative population), the conclusions did not differentiate between those with local-regional failures, distant metastasis, or both [6]. The purpose of this study was to thus assess the impact of HPV status on survival for patients with local-regionally recurrent HNSCC who underwent re-irradiation with external beam therapy, either as the primary modality or post-operatively after surgery, with the goal of determining whether HPV maintains its prognostic significance in this setting.

Section snippets

Study design

This study was approved by the institutional review board at our institution prior to the collection of all patient information. The medical records of 54 consecutive patients who underwent re-irradiation at a large tertiary-care comprehensive cancer center between April 2011 and January 2016 for local-regionally recurrent squamous cell carcinoma of the head and neck occurring in a previously irradiated field were reviewed. Only patients with biopsy-proven evidence of gross recurrent disease

Results

There were no significant differences in age (p = 0.08), gender (p = 0.2), smoking history, time interval between radiation courses (p = 0.80), performance status (p = 0.10), and use of concurrent chemotherapy (p = 0.30) between the HPV-positive and HPV-negative/unknown cohorts. Patients in the HPV-positive group (68.8%) were more likely to have received surgery prior to re-irradiation than those in the HPV-negative/unknown group (68.8% vs. 31.6%), (p = 0.01).

The median overall survival in the

Discussion

Although local-regional recurrences are relatively rare after definitive treatment for HPV-positive HNSCC, the recognition that they do occur coupled with the increasing incidence of this disease make it imperative to seek out therapeutic modalities for patients who present with recurrent disease [[7], [8], [9], [10]]. Our findings, suggesting that HPV-positive patients with local-regionally recurrent HNSCC are more likely to be salvaged with re-irradiation than those who are HPV-negative, are

Declarations of interest

None

Funding

None

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