Current Perspective on HPV-Associated Oropharyngeal Carcinomas and the Role of p16 as a Surrogate Marker of High-Risk HPV

Abstract

1 I. ústav patologie, LF MU a FN u sv. Anny v Brně 2 Klinika radiační onkologie, LF MU a Masarykův onkologický ústav, Brno 3 CEITEC -Středoevropský technologický institut, MU, Brno 4 Klinika komplexní onkologické péče, LF MU a Masarykův onkologický ústav, Brno SouhrnVýchodiska: Karcinomy orofaryngu asociované s lidským papilomavirem (human papillomavirus -HPV) nejen pro svou nadále vzrůstající incidenci představují významnou kapitolu v oblasti nádorů hlavy a krku. Tyto nádory oproti HPV negativním karcinomům orofaryngu disponují odlišnými epidemiologickými, klinickými i molekulárními vlastnostmi, lepší odpovědí na léčbu a prognózou. Vlivem těchto skutečností byla provedena celá řada studií, jejichž společným cílem bylo navržení adekvátního stagingového systému pro HPV asociované karcinomy orofaryngu, neboť 7. vydání American Joint Committee on Cancer nebralo v potaz unikátní bio logické chování tohoto onemocnění. Výsledkem jsou zásadní změny v TNM klasifikaci karcinomů orofaryngu, které jsou nyní v závislosti na expresi surogátního markeru high-risk HPV p16 členěny na p16 pozitivní a p16 negativní. Cíl: Cílem tohoto přehledového článku je nejen shrnutí aktuálních vědomostí o HPV asociovaných karcinomech orofaryngu s důrazem na jejich molekulární podklad a morfologii, ale také shrnutí a porovnání metod detekce viru HPV. Zároveň je diskutován prognostický význam exprese biomarkeru p16 u těchto nádorů. Součástí přehledového článku je dále představení změn ve stagingu karcinomů orofaryngu v závislosti na expresi markeru p16, vč. odůvodnění, která k těmto změnám vedla. SummaryBackground: The incidence of oropharyngeal carcinomas associated with human papillomavirus (HPV) is continuously increasing. HPV-positive and -negative oropharyngeal carcinomas have different epidemiological, clinical, and molecular features, with HPV-positive tumors having a better response to treatment and better prognosis. An adequate staging system for HPV-related oropharyngeal carcinomas is needed, as the American Joint Committee on Cancer 7 th Edition did not consider their unique bio logical behavior. At present, oropharyngeal carcinomas are subdivided into p16 positive and p16 negative tumors, based on their expression of p16, a surrogate marker of high--risk HPV. Purpose: This review summarizes current knowledge of HPV-associated oropharyngeal carcinomas with emphasis on their molecular features and histopathology, as well as summarizes and compares HPV detection methods and genotyping techniques. This review also describes the prognostic significance of p16 expression in these tumors and significant changes in the staging of oropharyngeal carcinomas based on p16 expression, together with the justifications for these changes.

The correlation and clinical significance of PIK3CA, PIK3CB and HPV infection in esophageal squamous cell carcinoma

“…A similar correlation possibly exists, because the esophagus may also be infected with HPV [25]. HPV-infected tumors are characterized by a high expression of p16, which is widely considered as an alternative marker for HPV infection in squamous cell carcinoma [10,12]. In the present study, the expression rate of p16 in ESCC was 30.8%, which was significantly higher than in normal esophageal mucosa.…”

“…In more than 90% of HPV-positive oropharyngeal cancer, p16 was overexpressed. The immunohistochemical evidence of p16 overexpression has been widely used to establish the correlation between HPV carcinogenic activity in cervical cancer and dysplasia [9][10][11]. The immunohistochemical detection of p16 overexpression may serve as a surrogate marker of functionally relevant HPV infection [10,12].…”

HPV Infection and its Relationship with Expression of PIK3CA, PIK3CB in Esophageal Squamous Cells Carcinoma

“…A similar correlation possibly exists, because the esophagus may also be infected with HPV. HPV-infected tumors are characterized by a high expression of p16, which is widely considered as an alternative marker for HPV infection [10,12]. In the present study, the expression rate of p16 in ESCC was 30.8%, which was signi cantly higher than in normal esophageal mucosa.…”

“…In more than 90% of HPVpositive oropharyngeal cancer, p16 was overexpressed. The immunohistochemical evidence of p16 overexpression has been widely used to establish the correlation between HPV carcinogenic activity in cervical cancer and dysplasia [9][10]. Several studies have shown that the immunohistochemical detection of p16 overexpression may serve as a surrogate marker of functionally relevant HPV infection [10][11].…”

<p>The Relationship Between Human Papillomavirus, OFD1 and Primary Ciliogenesis in the Progression of Oropharyngeal Cancer: A Retrospective Cohort Study</p>

“…11 Moreover, compared with the use of histochemical methods to detect HPV DNA, p16 expression can be used as an independent prognostic factor for overall survival and progression-free survival. 12 Then, p16 immunohistochemistry (IHC) in combination with HPV-DNA detection by PCR has been found to be a powerful indicator of clinical outcome in patients with OPSCC using univariate analysis. 7,13 And previous studies have indicated that p16 may enhance the immunogenicity of dendritic cells (DC) by means of Th1 cytokine secretion and cyclin-dependent pathways.…”