Does HPV type affect outcome in oropharyngeal cancer?

Abstract

BackgroundAn epidemic of human papillomavirus (HPV)-related oropharyngeal squamous cell cancer (OPSCC) has been reported worldwide largely due to oral infection with HPV type-16, which is responsible for approximately 90% of HPV-positive cases. The purpose of this study was to determine the rate of HPV-positive oropharyngeal cancer in Southwestern Ontario, Canada.MethodsA retrospective search identified ninety-five patients diagnosed with OPSCC. Pre-treatment biopsy specimens were tested for p16 expression using immunohistochemistry and for HPV-16, HPV-18 and other high-risk subtypes, including 31,33,35,39,45,51,52,56,58,59,67,68, by real-time qPCR.ResultsFifty-nine tumours (62%) were positive for p16 expression and fifty (53%) were positive for known high-risk HPV types. Of the latter, 45 tumors (90%) were identified as HPV-16 positive, and five tumors (10%) were positive for other high-risk HPV types (HPV-18 (2), HPV-67 (2), HPV-33 (1)). HPV status by qPCR and p16 expression were extremely tightly correlated (p < 0.001, Fishers exact test). Patients with HPV-positive tumors had improved 3-year overall (OS) and disease-free survival (DFS) compared to patients with HPV-negative tumors (90% vs 65%, p = 0.001; and 85% vs 49%, p = 0.005; respectively). HPV-16 related OPSCC presented with cervical metastases more frequently than other high-risk HPV types (p = 0.005) and poorer disease-free survival was observed, although this was not statistically significant.ConclusionHPV-16 infection is responsible for a significant proportion of OPSCC in Southwestern Ontario. Other high-risk subtypes are responsible for a smaller subset of OPSCC that present less frequently with cervical metastases and may have a different prognosis.

The Epidemic of Human Papillomavirus and Oropharyngeal Cancer in a Canadian Population

“…We currently favour real-time pcr, with all samples tested in triplicate and repeated if any discrepancies arise. We reported a very high correlation with p16 status 13 , and our method has the advantage of working with dna, which is significantly more stable than rna. The pcr techniques also offer the ability to carry out hpv type-specific testing, which may be important, because different hpv-types may portend a different prognosis, as is observed in cervical cancer 13,16 .…”

“…Deparaffinization, dna extraction, and detection of high-risk hpv types 16 and 18 by multiplex real-time polymerase chain reaction (pcr) was performed as previously described 13 . Standard curves were produced from 10-times serial dilutions of CaSki cell genomic dna.…”

Human papillomavirus associated head and neck squamous cell carcinoma: Controversies and new concepts

“…Subgroup analyses with p16+/HPV DNA+ patients and p16+/HPV RNA+ patients were also favorable. 52 (Table 1).…”

La infección por virus del papiloma humano afecta el pronóstico del cáncer orofaríngeo escamocelular. Revisión de la literatura / Human Papillomavirus Infection Affects Squamous Oropharyngeal Cancer Prognosis. Literature Review

“…Esto se debe a que los primeros producen degradación de la proteína p53, inactivación de la vía del retinoblastoma RB y aumento en la regulación de la proteína P16. Por otra parte, los segundos se caracterizan por la mutación del gen TP53 y la baja regulación de CDKN2A, que codifica para la proteína P16 (22,34).…”