RESUMEN
BACKGROUND: Human papillomaviruses (HPV) seem to be related to distant metastasis (DM) in advanced oral cavity squamous cell carcinoma (OSCC) patients. OBJECTIVES: This study aimed to investigate whether high-risk HPV viral load may predict DM among OSCC patients and stratify patients for risk-adapted treatment. STUDY DESIGN: Viral loads of E7 oncogenes for HPV 16/18 were measured by quantitative PCR tests in paraffin-embedded lesional specimens from 312 OSCC of which the HPV genotypes had been determined previously. Multivariable Cox regression analysis was used to identify the independent prognostic factors for 5-year DM and C statistics were further computed. RESULTS: By multivariable analysis, high HPV 16 E7 viral load (≥15.0 copies/genome); high HPV 18 E7 viral load (≥15.0 copies/genome); pathological N2 status (pN2); tumor depth ≥11 mm; extracapsular spread (ECS); and level IV/V metastases were independent risk factors for DM. We further identified three prognostic groups. In the high-risk group (level IV/V metastases or high HPV 16/18 E7 viral load plus pN2, tumor depth ≥11 mm, or ECS), the 5-year distant metastasis rate was 74%. In the intermediate-risk group (high HPV 16/18 E7 viral load, pN2, tumor depth ≥11 mm, or ECS), the 5-year DM rate was 17%. Finally, the 5-year DM rate was 1% in the low-risk group (no risk factors). The value of the C statistics was 0.78. CONCLUSIONS: Among OSCC patients, high HPV 16/18 E7 viral load identifies a small subgroup of patients at high-risk of 5-year DM and suggest the need for more intensive treatments and follow-up strategies.
Asunto(s)
Carcinoma de Células Escamosas/diagnóstico , Papillomavirus Humano 16/aislamiento & purificación , Papillomavirus Humano 18/aislamiento & purificación , Neoplasias de la Boca/diagnóstico , Metástasis de la Neoplasia/diagnóstico , Carga Viral , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/secundario , Carcinoma de Células Escamosas/virología , Proteínas de Unión al ADN/genética , Femenino , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/complicaciones , Proteínas Oncogénicas Virales/genética , Proteínas E7 de Papillomavirus/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Estudios RetrospectivosRESUMEN
BACKGROUND: Although human papillomavirus (HPV) infections have been causally linked to oral cavity squamous cell carcinoma (OSCC), the potential role of low-risk HPV (LR-HPV) types in the pathogenesis of this malignancy remains unclear. OBJECTIVES: We sought to investigate the distribution of HPV genotypes and their prognostic significance in OSCC patients treated by radical surgery, either with or without adjuvant therapy. STUDY DESIGN: We studied two non-overlapping OSCC cohorts for the periods 2005-2006 (2005 cohort, n = 204) and 2010-2011 (2010 cohort, n = 206). Paraffin-embedded tissue blocks were collected, and the HPV genotype was determined using PCR plus HPV blot tests. The primary study endpoint was the prevalence of HPV genotypes. The secondary endpoints were the 2-year therapeutic outcomes. RESULTS: The overall prevalence of HPV infections did not differ significantly in the two study cohorts. However, the prevalence of LR-HPV was significantly higher in the 2010 cohort than in the 2005 cohort (p = 0.002). The overall prevalence of HPV infections was not significantly associated with the 2-year outcomes. However, multivariate analysis demonstrated that LR-HPV infection was a predictor of poor 2-year disease-free survival (p = 0.036, hazard ratio [HR] = 3.1), disease-specific survival (p = 0.014, HR = 3.8), and overall survival (p = 0.016, HR = 3.2) in the subgroups of OSCC patients with poor differentiation, pN2 lymph node metastases, or extracapsular spread (n = 150). CONCLUSIONS: LR-HPV infections may have an important role in determining the clinical outcomes of certain OSCC patients bearing specific risk factors.