Expression of toll-like receptors in HPV-positive and HPV-negative oropharyngeal squamous cell carcinoma—an in vivo and in vitro study

Abstract

The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has increased over the past decades in many western countries. This trend is mainly attributed to the human papillomavirus (HPV). Cancer-related actions of immunological defense systems are being intensively researched. Human toll-like receptors (TLRs) are a family of pattern recognition receptors that participate in the immunological defense against pathogens, but their actions are also linked to cancer. The expression of TLRs in cervical epithelium alters both during the clearance of HPV infection and the HPV-induced neoplasia, but the expression of TLRs has not been studied in OPSCC. Thirty-five paraffin-embedded, formalin-fixed, squamous cell carcinoma tissue specimens were analyzed for TLRs 2, 3, 4, 5, 7, and 9 and HPV and p16 statuses. The TLR 9 expression was lower in HPV-positive tumors compared with HPV-negative tumors. TLR 7 was expressed in all cancer specimens, but elevated expression was evident in HPV and/or p16-positive tumors. The majority of p16-positive tumors did not express TLR 5, whereas its expression was stronger in p16-negative tumors. The results of in vitro analysis of five human OPSCC cell lines and one human oral tongue squamous cell carcinoma cell line agree with the in vivo trends: low levels of TLR 5 and high levels of TLR 7 in p16-positive OPSCC. Overall, TLR 7 and 9 expression patterns are demonstrated here to relate to the HPV status in vivo and TLR 5 and 7 expression patterns to the p16 status in vivo and in vitro.

TLR5 and TLR7 are differentially expressed in human papillomavirus-positive and negative base of tongue squamous cell carcinoma, and TLR7 may have an independent prognostic influence

“…in a specific subtype of OPSCC), as has been previously shown in HPV þ and HPV À OPSCC and whether TLR5 and TLR7 expression would correlate with survival in HPV þ BOTSCC [15]. Our results confirmed that absent/weak TLR5 and medium/strong TLR7 expression was more frequently found in HPV þ compared with HPV À BOTSCC [15,20]. However, it was not possible to confirm with statistical significance that moderate/strong TLR5 or absent/weak TLR7 expression would correlate with worse outcome irrespective of tumor HPV status.…”

Changing trends in the management of the neck in oropharyngeal squamous cell carcinoma

“…The histopathological tissue blocks of primary tumors and neck recurrences were obtained to study protein p16 expression. We used the tissue microarray (TMA) method for primary tumors and whole tissue blocks for regional recurrences, as described elsewhere . For TMA analysis, 3 samples were taken from each tumor.…”

“…We used the tissue microarray (TMA) method for primary tumors 13 and whole tissue blocks for regional recurrences, as described elsewhere. 14 3 | R E S U L T S…”

Expressão dos receptores Toll-like em carcinoma espinocelular de orofaringe

“…Ainda existem muitas contradições e mais estudos são necessários. Em cabeça e pescoço, existe apenas um estudo(68) avaliando alguns dos receptores Toll-likes. Este é o primeiro estudo em orofaringe avaliando todos os 10 TLRs e a função dos principais receptores.…”

“…Em carcinoma de colo de útero, estudos demonstraram aumento da expressão de TLR9 em mulheres que apresentavam HPV persistente (67) e em mulheres que apresentavam eliminação do vírus(9). O aumento de TLR9 é devido ao reconhecimento do vírus pelo receptor e consequente ativação do sistema imune para a tentativa de eliminação do vírus.Entretanto, o estudo realizado com CECOF HPV+ demonstrou diminuição de TLR9(68), assim como outros estudos com carcinoma de colo de útero, demonstraram que TLR9 apresentava baixa expressão. Esta diminuição ocorre como forma de escape do HPV do sistema imune e persistência na célula.…”