Reduced-Dose Radiotherapy Proposed For HPV-Positive Oropharyngeal SCC

Human papillomavirus-positive oropharyngeal squamous cell carcinoma may have increased radiation sensitivity that could allow a reduced dose radiotherapy protocol

medwireNews: A reduced dose of radiotherapy may be feasible in patients with human papillomavirus (HPV)-positive squamous cell carcinoma (SCC) of the oropharynx, say US researchers who believe this could improve treatment tolerability without affecting survival outcomes.

“This treatment approach seems to hold considerable promise for a disease that is rapidly increasing in incidence”, write Allen Chen, from the University of California, Los Angeles in the USA, and co-authors in The Lancet Oncology.

Their phase II trial included patients with HPV-positive disease confirmed by p16 testing and a good performance status who were given two cycles of induction paclitaxel and carboplatin, followed by intensity-modulated radiotherapy with daily image guidance plus weekly paclitaxel.

Over half (55%) of 44 patients had a complete or partial response to induction chemotherapy and were given 54 Gy of radiation over 27 fractions, while the remainder received 60 Gy over 30 fractions.

After a median of 30 months, just three (7%) patients had developed locoregional recurrence and one (2%) distant metastases, giving a 2-year progression-free survival rate of 92%.

Grade 3 adverse events were reported in 39% of patients; leukopenia and neutropenia were the most common grade 3 side effects during induction chemotherapy, while dysphagia and mucositis were the most frequent during chemoradiotherapy. One individual was dependent on a gastrostomy tube after 3 months but none of the patients required this intervention by 6 months.

“We believe that reduced-dose regimens have the potential to usher in a new standard of care for a disease in which the radiation dose has largely been the same for upwards of 50 years and might be exposing patients with HPV-positive head and neck cancers to overtreatment and an unacceptably high risk of toxic effects”, the researchers conclude.

“A phase 3 study to investigate the efficacy of our regimen further is being planned.”

However, the authors of an accompanying comment observe that using p16 testing alone may have inadvertently included a small subset of HPV-negative patients with a poorer prognosis than expected for the HPV-positive population.

Moreover, the commentators note that several positive prognostic features were common in the study population, such as high-volume tumours occurring in just 18% of patients, and 68% of patients never having smoked and none were active smokers at time of trial entry.

“These characteristics might have contributed to the excellent results achieved”, say Ricard Mesía and Miren Taberna, from the University of Barcelona in Spain.

And the commentators emphasize: “Importantly, Chen and colleagues reduced the radiation dose not only for responders but also for non-responders, who received 60 Gy radiation instead of about 70 Gy, which is accepted as the standard dose.”

They therefore conclude: “The investigators need to confirm whether the patients with minimum smoking history and low-volume tumours achieved the best disease control.

“If so, these patients are the most appropriate candidates for de-escalation treatment, and other patients with HPV-related oropharyngeal squamous-cell carcinoma should continue to receive standard therapy for now.”


Chen AM, Felix C, Wang P-C, et al. Reduced-dose radiotherapy for human papillomavirus-associated squamous-cell carcinoma of the oropharynx: a single-arm, phase 2 study. Lancet Oncol; Advance online publication 20 April 2017. DOI:

Mesía R, Taberna M. HPV-related oropharyngeal carcinoma de-escalation protocols. Lancet Oncol; Advance online publication 20 April 2017. DOI:

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