Human Papillomavirus and Survival of Patients with Oropharyngeal Cancer
- Study type
- Observational study
- Design
- Retrospective (post hoc, outside the protocol) analysis of tumour HPV status and survival in oropharyngeal cancer patients enrolled in the phase 3 randomised trial RTOG 0129 (accelerated radiotherapy with concomitant boost versus standard radiotherapy, both with high-dose cisplatin)
- Sample size
- 721 eligible patients in RTOG 0129; 433 oropharyngeal cancer patients, with HPV status determined in 323 (206 HPV-positive)
- Source
- N Engl J Med · 2010
- Trial registration
- NCT00047008
In plain words
This study found that people whose oropharyngeal cancer (cancer of the part of the throat behind the mouth) is linked to the human papillomavirus (HPV) live markedly longer after treatment with radiotherapy and cisplatin. After 3 years, 82.4% of patients with HPV-positive tumours were alive, compared with 57.1% of patients with HPV-negative tumours. Smoking also raises the risk of death, and the more someone has smoked, the higher this risk.
Key results
Treatment arms and regimens
Radiotherapy: 72 Gy in 42 fractions over 6 weeks, with a concomitant boost given as twice-daily irradiation on 12 treatment days.
Cisplatin: 100 mg/m² IV on days 1 and 22 (2 doses).
360 patients.
Radiotherapy: 70 Gy in 35 fractions (2 Gy per fraction) over 7 weeks.
Cisplatin: 100 mg/m² IV on days 1, 22 and 43 (3 doses).
361 patients.
Source of the regimen details: Full text of the paper (author manuscript in PMC2943767)
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
RTOG 0129 trial (July 2002 to May 2005; 743 randomised patients, 721 eligible patients): previously untreated, pathologically confirmed stage III or IV squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx without distant metastasis (M0); Zubrod performance status 0 or 1; age 18 years or older; adequate bone marrow, hepatic and renal function. Stratified by tumour site (larynx versus other), N stage and performance status.
The HPV analysis was limited to the 433 patients with oropharyngeal cancer (60.1%), and HPV status was determined in 323 (74.6%) by in situ hybridisation (HPV-16, then 12 other high-risk types); p16 expression was also assessed by immunohistochemistry (strong, diffuse staining in 70% or more of tumour cells = positive).
Endpoints
Primary endpoint of the trial: overall survival (from randomisation to death). Secondary: progression-free survival and its components (locoregional failure and distant metastasis) and second primary tumours. The HPV status analysis was a post hoc subgroup analysis not prespecified in the protocol. Median follow-up 4.8 years (range 0.3 to 6.5).
Safety and side effects
There were no significant differences between the two groups: death within 30 days of starting treatment 3.3% (accelerated) versus 1.9% (standard; P=0.26); acute grade 3 or 4 adverse events: 80.0% versus 83.7% (P=0.21); late grade 3 or 4 adverse events: 25.7% versus 21.1% (P=0.18).
Both regimens are high-dose cisplatin chemoradiotherapy, and the rate of severe acute adverse events is above 80%.
Clinical significance and place in guidelines
This analysis showed that tumour HPV status (and p16 as a surrogate marker) is a strong and independent prognostic factor in oropharyngeal cancer, and together with tobacco use (more than 10 pack-years) and T and N stage it divides patients into three risk groups. The RTOG 0129 trial itself showed that accelerated radiotherapy with cisplatin has no survival advantage over standard radiotherapy with three doses of cisplatin.
Limitations
The HPV analysis was retrospective and post hoc, and grouping by HPV status was not randomised; HPV status was determined in only 74.6% of oropharyngeal cancer patients (although no differences in characteristics or survival were seen between patients with and without an HPV result). All patients received high-dose cisplatin chemoradiotherapy, and these data do not justify treatment de-intensification in HPV-positive disease.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.