Differential outcome of concurrent radiotherapy plus epidermal growth factor receptor inhibitors versus radiotherapy plus cisplatin in patients with human papillomavirus-related head and neck cancer

Abstract

BackgroundHuman papillomavirus (HPV)-related head and neck cancer has been associated with an improved prognosis in patients treated with radiotherapy (RT) +/− chemotherapy (CT); however, RT combined with epidermal growth factor receptor (EGFR) inhibitors has not been fully studied in this group of patients.MethodsImmunohistochemical expression of p16 and PCR of HPV16 DNA were retrospectively analyzed in tumor blocks from 108 stage III/IV head and neck cancer patients treated with RT+CT (56) or RT+EGFR inhibitors (52). Disease-free survival (DFS) and overall survival (OS) were analyzed by the Kaplan-Meier method.ResultsDNA of HPV16 was found in 12 of 108 tumors (11%) and p16 positivity in 18 tumors (17%), with similar rates in both arms of treatment. After a median follow-up time of 35 months (range 6–135), p16-positive patients treated with RT+EGFR inhibitors showed improved survival compared with those treated with RT+CT (2-year OS 88% vs. 60%, HR 0.18; 95% CI 0.04 to 0.88; p = 0.01; and 2-year DFS 75% vs. 47%, HR 0.17; 95% CI 0.03 to 0.8; p = 0.01). However, no differences were observed in p16-negative patients (2-year OS 56% vs. 53%, HR 0.97; 95% CI 0.55 to 1.7; p = 0.9; and 2-year DFS 43% vs. 45%, HR 0.99; 95% CI 0.57 to 1.7; p = 0.9).ConclusionsThis is the first study to show that p16-positive patients may benefit more from RT+EGFR inhibitors than conventional RT+CT. These results are hypothesis-generating and should be confirmed in prospective trials.

Re-irradiation with cetuximab or cisplatin-based chemotherapy for recurrent squamous cell carcinoma of the head and neck

“…On the other hand, other studies failed to identify any differences in disease control and survival [27,28]. Interestingly, Pajares et al observed a survival benefit in favour of cetuximab for the subgroup of patients with HPV p16-positive SCCHN [29]. The contrasting observation (in favour of cisplatin) was reported for a group of 174 patients after accounting for HPV status [30].…”

Subcellular localisation of pMEK has a different prognosis in locally advanced head and neck cancer treated with concomitant radiochemotherapy

“…The lower p16 positive prevalence in our patients compared with data from different meta-analysis (22–34 % in HNSCC and 30–41 % in OPSCC) [11, 12] confirms the previous results published by our group [9, 13] and is possibly due to the epidemiologic profile of our population, which had a high proportion of heavy tobacco users. In this study, the vast majority of our patients were current smokers (95 %), and only two patients were p16 positive and non-smokers.…”

“…Tumours were considered to have a high proliferative index if Ki-67 was positive in >/= 20 % of the cells [8]. Expression of p16 was classified dichotomously as either p16-positive (strong, diffuse staining) or p16 negative [9]. Regarding pMEK, patients were divided considering staining intensity in absence of expression (0), low intensity (+1), moderate intensity (+2) and high intensity (+3).…”

Comparison of systemic therapies used concurrently with radiation for the treatment of human papillomavirus–associated oropharyngeal cancer

“…However, these studies were more general and did not focus on patients with HPV‐associated disease. The retrospective trial conducted by Pajares et al suggested that patients with p16‐positive tumors may benefit more from radiotherapy plus cetuximab than conventional radiotherapy concurrent with cisplatin. In comparison, our study focusing on over 300 patients with HPV‐associated oropharyngeal cancer demonstrated that outcome differences for patients are similar between those treated with either cetuximab or cisplatin.…”