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Circulating neutrophil, monocyte, lymphocyte counts predict survival in HPV-positive oropharyngeal cancer
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Both high pretreatment circulating neutrophil and monocyte counts independently predicted shorter OS and RFS among patients with HPV-positive oropharyngeal cancers, according to study results.
High circulating lymphocyte counts predicted improved RFS and slightly better OS in the same patient population, results showed. However, none of these factors appeared associated with survival in patients with HPV-negative patients, results showed.
Shao Hui Huang, MSc, MD, MRT(T), of the department of radiation oncology at Princess Margaret Cancer Center of the University of Toronto, and colleagues sought to assess the prognostic value of pretreatment circulating neutrophil, monocyte and lymphocyte counts among patients with HPV-positive (n=510) and HPV-negative (n=192) oropharyngeal cancers.
All patients underwent chemoradiotherapy between 2000 and 2010. Median follow-up was 4.8 years.
Investigators observed lower circulating neutrophil and monocyte counts among patients with HPV-associated vs. those with non-HPV–associated oropharyngeal cancer. Circulating lymphocyte counts (P<.01) were similar between the two groups.
Among patients with HPV-positive cancers, high circulating neutrophil and monocyte counts were associated with shorter OS and RFS compared with low counts (P<.01 for both). Researchers observed no association between circulating lymphocyte counts and either OS (P=.3) or RFS (P=.1).
Results of multivariate analysis confirmed that high circulating neutrophil and monocyte counts independently predicted shorter OS (HR=1.14; P<.01 for circulating neutrophil count; HR=2.95; P<.01 for circulating monocyte counts) and shorter RFS (HR=1.11; P<.01 for circulating neutrophil count; HR=3.39; P<.01, for circulating monocyte counts) in HPV-associated oropharyngeal cancers.
In that same subset of patients, multivariate analysis showed a higher circulating lymphocyte count was associated with longer RFS (HR=0.66; P=.03) and marginally improved OS (HR=0.8; P=.08).
Conversely, among patients with HPV-negative oropharyngeal cancers, researchers observed no association between survival and circulating neutrophil (P=.16 for OS; P=.61 for RFS), monocyte (P=.86 for OS; P=.59 for RFS) and lymphocyte (P=.14 for OS; P=.62 for RFS) counts.
“Circulating neutrophil, monocyte and lymphocyte counts may be important and objective clinical factors for further stratifying the risk of disease failure for the HPV-positive population if non–cancer–related circulating neutrophil, monocyte and lymphocyte count variations can be differentiated,” Huang and colleagues wrote. “Further study is needed to understand the biology of this observation and to potentially identify new therapeutic targets.”
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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Cristina Rodriguez, MD
The emergence of the prognostically superior and biologically distinct HPV-positive oropharynx population has led to de-intensification of therapy as an intuitive approach in clinical trial design. Despite this, it is clear that this population is heterogeneous, with a proportion that does poorly. This was evident in a report by Ang and colleagues (Ang KK. N Engl J Med. 2010;doi:10.1056/NEJMoa0912217), which demonstrated that HPV-positive patients with oropharyngeal cancers who had a greater than 10 pack-year smoking history had statistically inferior outcomes compared with those who had less than a 10 pack-year smoking histories.Identifying biomarkers that can successfully risk stratify these patients is a key approach toward designing clinical trials and tailoring patient treatment to optimize oncologic outcomes, as well as to minimize acute and late toxicity. There is tremendous enthusiasm regarding insights into the relationship of immune cells and malignant cells. This paper demonstrated that higher peripheral neutrophil and monocyte counts, and lower peripheral lymphocyte counts, are associated with poorer survival and therapeutic outcomes in HPV-positive patients. The strength of the paper is its large population of patients, treated uniformly in one institution.
Validation of this observation in a prospective fashion, and correlating with intratumoral immune cell phenotype, are promising steps toward identifying high-risk patients who may be less suitable for therapeutic de-intensification.
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