Contribution of human papilloma virus to the incidence of squamous cell carcinoma of the head and neck in a European population with high smoking prevalence

Tinhofer, Ingeborg; Jöhrens, Korinna; Keilholz, Ulrich; Kaufmann, Andreas M.; Lehmann, Annika; Weichert, Wilko; Stenzinger, Albrecht; Stromberger, Carmen; Klinghammer, Konrad; Becker, Eva-Tessina; Dommerich, Steffen; Stölzel, Katharina; Hofmann, Veit Maria; Hildebrandt, Bert; Moser, Lutz; Ervens, J.; Böttcher, Arne; Albers, Andreas E.; Stabenow, Roland; Reinecke, Annette; Budach, Volker; Hoffmeister, Bodo; Raguse, Jan-Dirk

doi:10.1016/j.ejca.2014.12.018

Cited by 76 publications

(59 citation statements)

References 21 publications

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“…No significant correlations between the expression of ALDH1A1 or HMGB1 and p16 were found. Furthermore, p16 did not predict survival time in this study population of patients with OSCC, which had also been recently shown for European populations (37), but was in contrast with studies from the United States of America (38). This is probably due to less cessation of tobacco abuse in European regions.…”

Section: A B C Dcontrasting

confidence: 55%

Expression of aldehyde dehydrogenase family 1 member A1 and high mobility group box 1 in oropharyngeal squamous cell carcinoma in association with survival time

et al. 2016

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Abstract. Despite the development of novel multimodal treatment combinations in advanced oropharyngeal squamous cell carcinoma (OSCC), outcomes remain poor. The identification of specifically validated biomarkers is required to understand the underlying molecular mechanisms, to evaluate treatment efficiency and to develop novel therapeutic targets. The present study, therefore, examined the presence of aldehyde dehydrogenase family 1 member A1 (ALDH1A1) and high mobility group box 1 (HMGB1) expression in primary OSCC and analyzed the impact on survival time. In 59 patients with OSCC, the expression of ALDH1A1, p16 and HMGB1, and their clinicopathological data were analyzed. HMGB1 positivity was significantly increased in patients with T1-2 stage disease compared with T3-4 stage disease (P<0.001), whereas ALDH1A1 positivity was not. ALDH1A1 + tumors showed significantly lower differentiation than ALDH1A1 -tumors (P=0.018). Multivariate analysis showed that ALDH1A1 positivity (P=0.041) and nodal status (N2-3) (P=0.036) predicted a poor prognosis. In this patient cohort, ALDH1A1 and nodal status were identified as independent predictors of a shorter overall survival time. The study results, therefore, provide evidence of the prognostic value of ALDH1A1 as a marker for cancer stem cells and nodal status in OSCC patients. IntroductionHead and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, with an annual incidence of 500,000 new cases and 200,000 mortalities (1,2). Oropharyngeal squamous cell carcinoma (OSCC) is a subtype of HNSCC arising from the oropharynx, which includes anatomically the base-of-the tongue, the tonsils, the soft palate and the side and back wall of the throat. The incidence rates for cancer sites in the oropharynx, such as the tonsils and the base of the tongue, are associated with a rise in human papilloma virus (HPV) infections, but a decreased number of tobacco-and alcohol-related cancers (3). In recent decades, there have been a number of important advances in the standard treatment of HNSCC, including surgical innovations for early-stage tumor patients and novel multimodal treatment combinations for more advanced-stage tumors, such as surgery followed by adjuvant radiotherapy (RT) or chemoradiotherapy (CRT), or CRT alone (4). However, outcomes remain poor in advanced tumor stages due to frequent local and regional metastases, and resistance to therapy (5,6). Therefore, identification of specific validated biomarkers is required to understand the underlying molecular mechanisms, evaluate treatment efficiency and develop novel therapeutic targets.High mobility group box 1 (HMGB1) is a nuclear, non-histone, chromatin-binding protein (7) that has been implicated in the activities of various cell type, including enterocytes, cardiomyocytes, pituicytes, macrophages and monocytes (8-11). HMGB1 is defined as one of the damage-associated molecular pattern molecules that interact with a variety of pattern recognition receptors in the microenvironment of damaged or necrot...

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Section: A B C Dcontrasting

confidence: 55%

Expression of aldehyde dehydrogenase family 1 member A1 and high mobility group box 1 in oropharyngeal squamous cell carcinoma in association with survival time

et al. 2016

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“…However, in future, as more data are available, such geographic distinctions may become relevant, since tobacco consumption and the incidence of HPV infection show differences between countries and continents [4,10,61]. Cofactors such as smoking behavior may impact the prevalence and presence of the two markers HPV and p16, but not the survival of the distinct subgroups [8,72]. In 50 % of the studies the detection of HPV was associated with non-smoking.…”

Section: Discussionmentioning

confidence: 99%

“…Smoking, however, has been shown to be an independent risk factor of reduced treatment efficiency and OS in HPV-related carcinomas [2,20,45]. Efforts to investigate prospectively relationships between tobacco consumption, HPV and p16 status and survival have been initiated at our institution [72]; however, data for the distinct subgroups are not yet available.…”

Section: Discussionmentioning

confidence: 99%

Meta-analysis of survival in patients with HNSCC discriminates risk depending on combined HPV and p16 status

Coordes

Lenz

Qian

et al. 2015

Eur Arch Otorhinolaryngol

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Data indicate a better prognosis for human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC). HPV and p16 detection are established markers for HPV-related HNSCC. Both are accepted as survival-independent predictors. Previous studies investigating the survival in HNSCC patients depending on HPV(+/-) and p16(+/-) status consistently found discordant results with p16(-)/HPV(+) and p16(+)/HPV(-). However, no meta-analysis regarding the survival according to combined HPV/p16 status has been performed yet. The objective of this study was to discriminate the impact of combined HPV(+/-) and p16(+/-) status on survival. Data sources were identification and review of publications assessing survival of the distinct subgroups with both p16 and HPV investigated in HNSCC until February, 2015. A meta-analysis was performed to classify survival and clinical outcomes. 18 out of 397 articles (4424 patients) were eligible for the meta-analysis. The percent proportion of the subgroups was 25 % for HPV(+)/p16(+), 61.2 % for HPV(-)/p16(-), 7.1 % for HPV(-)/p16(+) and 6.8 % for HPV(+)/P16(-). The meta-analysis showed a significantly improved 5-year overall survival (OS), 5-year disease-free survival and their corresponding hazard ratio for HPV(+)/p16(+) HNSCC in comparison to HPV(-)/p16(-), HPV(+)/p16(-) and HPV(-)/p16(+). The 5-year OS of the HPV(-)/p16(+) subgroup was intermediate while HPV(+)/p16(-) and HPV(-)/p16(-) HNSCC had the shortest survival. With current therapeutic strategies, survival of patients with HNSCC is better if associated with HPV(+)/p16(+) or HPV(-)/p16(+). Clinical trials are needed to confirm the distinct survival pattern and to investigate possible differences in survival for HPV(+)/p16(-) and HPV(-)/p16(+) HNSCC. To further differentiate p16(+) HNSCC, HPV testing may be advisable.

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“…Die größe-re Gruppe dieser Tumoren, insbesondere Neoplasien der Mundhöhle, des Hypopharynx und des Larynx sind nach wie vor in der Regel mit langjährigem Tabakund Alkoholkonsum assoziiert, während eine zweite Familie von HNSCC heute als virusgetriggerte Tumoren in Assoziation mit einer Infektion mit dem humanen Papillomavirus (HPV) verstanden wird. Letztere Tumoren finden sich zumeist oropharyngeal [13], sprechen besser auf Radiochemotherapie an und sind prognostisch günstiger [7].…”

Section: Epidemiologie Und Biologieunclassified

Grading von Tumoren der Kopf‑Hals‑Region

Agaimy

Weichert

2016

Pathologe

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Tumors of the head and neck form a heterogeneous group of benign and malignant neoplasms with significant differences in biological behavior and therapeutic strategies. Squamous cell carcinomas (SCC) of the larynx, pharynx and oral cavity represent the most frequent and, thus, clinically most important malignant neoplasms in this anatomical region. Similar to other neoplasms, grading of head and neck malignancies is based on evaluation of the tumor histology usually including both architectural and cytological features; however, the current consensus grading for head and neck SCC is of limited prognostic and therapeutic value and the reproducibility is low. Therefore, novel grading criteria have been proposed that are based on additional parameters, such as the type of tumor growth pattern at the invasive front (so-called tumor budding). These novel algorithms, however, have not yet been officially endorsed into guidelines. Salivary gland (SG) neoplasms, although less frequent, constitute a second important pathologically and clinically complex group of tumors at this location. In contrast to SCC, grading of these tumors is of high clinical importance. Based on the large variety of carcinoma entities of the SG, both entity-specific (e. g. mucoepidermoid carcinoma) algorithms but also algorithms, which are solely based on the recognition of a specific carcinoma variant with subsequent automatic assignment of the tumor grade (e. g. acinic cell carcinoma and salivary duct carcinoma) are in use. In the sinonasal tract, grading is important for non-intestinal type adenocarcinoma and esthesioneuroblastoma. In this article the most important grading schemes and criteria for head and neck malignancies are presented and their prognostic and therapeutic implications are discussed.

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Contribution of human papilloma virus to the incidence of squamous cell carcinoma of the head and neck in a European population with high smoking prevalence

Cited by 76 publications

References 21 publications

Expression of aldehyde dehydrogenase family 1 member A1 and high mobility group box 1 in oropharyngeal squamous cell carcinoma in association with survival time

Expression of aldehyde dehydrogenase family 1 member A1 and high mobility group box 1 in oropharyngeal squamous cell carcinoma in association with survival time

Meta-analysis of survival in patients with HNSCC discriminates risk depending on combined HPV and p16 status

Grading von Tumoren der Kopf‑Hals‑Region

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