Patients with HPV-Positive N2c Disease Should Receive Chemotherapy to Prevent Distant Metastasis

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(ChemotherapyAdvisor) – Patients with human papillomavirus (HPV) categorized as T1-3N0-2c have a low risk of distant metastasis; however, those with N2c from this group have a reduced distant control when treated with radiotherapy (RT) alone, suggesting they are “less suited for deintensification strategies that omit chemotherapy,” a study reported in the Journal of Clinical Oncology published online ahead of print on January 7, 2013.

Calling distant metastasis in HPV-related oropharyngeal cancer “an enigma” and noting that “with the rarity of locoregional failure, distant metastasis seems now to be the leading cause of death in HPV-positive patients,” Brian O'Sullivan, MD, of Princess Margaret Hospital, Toronto, Ontario, Canada, and colleagues sought to define HPV-positive oropharyngeal cancers suitable for treatment deintensification according to low risk of distant metastasis.

Patients with oropharyngeal cancers treated with RT or chemoradiotherapy from 2001 to 2009 were included in the study and outcomes for HPV-positive versus HPV-negative patients compared. In 505 (56%) of the 899 consecutive cases, HPV status was ascertained; median follow-up was 3.9 years.

The 382 HPV-positive patients had higher local (94%) and regional (95%) control when compared with the 123 HPV-negative patients (80% and 82%, respectively; both P<0.01); however, distant control was similar: 90% vs 86% (P=0.53).

“Multivariate analysis identified that HPV negativity (hazard ratio [HR] 2.9; 95% CI: 2.0−5.0), N2b-N3 (HR 2.9; 95% CI: 1.8−4.9), T4 (HR 1.8; 95% CI, 1.2−2.9), and RT alone (HR 1.8; 95% CI, 1.1−2.5) predicted a lower recurrence-free survival (RFS; all P<0.01),” the investigators reported.

More than 10 smoking pack-years reduced overall survival (HR 1.72; 95% CI: 1.1−2.7; P=0.03) but had no effect on RFS (HR, 1.1; 95% CI, 0.7 to 1.9; P=0.65).

Using recursive partitioning analysis, HPV-positive patients were segregated into low (T1-3N0-2c; DC, 93%) and high risk of distant metastasis (N3 or T4; DC, 76%) and HPV-negative patients into different low (T1-2N0-2c; DC, 93%) and high distant metastasis risk (T3-4N3; DC, 72%) groups.

“Distant control rates for HPV-positive, low-risk N0-2a or less than 10 pack-year N2b patients were similar for RT alone and chemoradiotherapy, but the rate was lower in the N2c subset managed by RT alone (73% v 92% for CRT; P=0.02),” Dr. O'Sullivan noted.

An accompanying editorial noted, “Future deintensification protocols should consider not only the risk level but the pattern of relapse for the HPV-associated OPSCC [oropharyngeal squamous cell carcinoma], as well as how deintensification is achieved. Future longitudinal studies to further characterize the natural history of this high-risk cohort are needed to define a more strategic and cost-effective long-term surveillance plan.”


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