Role of human papillomavirus in the development of head and neck squamous cell carcinomas

Hafkamp, Harriët C.; Manni, Johannes J.; Speel, Ernst J. M.

doi:10.1080/00016480310016893

Cited by 80 publications

(75 citation statements)

References 15 publications

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“…The absence of p53 mutations in the tumor cell may allow an enhanced response to radiotherapy (Tachezy et al, 2005;Hoffmann et al, 2005). Hafkamp et al suggested that radiotherapy may decrease the ability of HPV-E6 and E7 to interact with p53 and pRb which supported the hypothesis above (Hafkamp et al, 2004). However, Ritchie et al found no statistically significant interaction between HPV status and radiotherapy on survival in oral and oropharyngeal cancers by considering separate effects for surgery and radiotherapy (Ritchie et al, 2003).…”

Section: Discussionmentioning

confidence: 60%

Human Papillomavirus as an Independent Predictor in Oral Squamous Cell Cancer

Zhao

Chen

et al. 2009

Int J Oral Sci

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AimThere is an increasing evidence for the role of high risk human papillomavirus (HPV) in the pathogenesis of oral squamous cell carcinoma (OSCC). The purpose of this study is to evaluate the relevance of HPV infection to the survival and prognosis of OSCC. Methodology Fifty-two patients with OSCC were followed from 4 to 88 months with a median of 50. Conclusion HPV infection can act as an independent predictor for the survival and prognosis of OSCC.

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Section: Discussionmentioning

confidence: 60%

Human Papillomavirus as an Independent Predictor in Oral Squamous Cell Cancer

Zhao

Chen

et al. 2009

Int J Oral Sci

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“…The tonsil has squamous epithelium on the surface and reticulated epithelium in the crypts and may undergo metaplastic processes, producing an environment that may favour HPV infection and transformation, like in the cervical epithelium. It has been suggested that HPV-positive tonsillar carcinomas represent a separate tumour entity, which is less dependent on conventional HNSCC risk factors (29).…”

Section: Discussionmentioning

confidence: 99%

Molecular analyses and prognostic relevance of HPV in head and neck tumours

Badaracco¹,

Rizzo

Mafera

et al. 2007

Oncol Rep

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Abstract. HPV involvement in head and neck (HN) cancer is still under active investigation. Fresh frozen and archival clinical samples from 115 patients affected by HN carcinomas were analysed by PCR-based methods and direct sequencing. HPV types, intra-type variants, physical status, viral load and viral transcript presence were determined. HPV positivity was correlated with the main clinical-pathological features, including smoker and drinker status, and the clinical outcome. Twenty-one tumours were HPV positive (18.3%) with HPV16 being the most frequent type (n=14) followed by HPV6 (n=4), HPV33, HPV35, and HPV58 (n=1, each type). Tonsil carcinomas contained more high-risk HPV types (6/8; 75%) than all other sites (p=0.0004). HPV16 genome was integrated in all analysed tumours, as pure integrated form or mixed with concomitant episomal forms (4 cases). The viral load showed a wide variability (range, 0.7-485 copies per cell) with the highest value detected in a larynx tumour and the lowest one in a case of cancer of the oral cavity. In 9 HPVpositive samples where mRNA was available, transcripts of viral early oncogenes originating by integrated, episomal or mixed forms of the viral genome were found. A statistically significant correlation was evidenced between HPV and tumour differentiation, being the virus more associated with tumour grade G3/G4. Multivariate Cox regression analysis revealed that lymph-node and grade status were significant independent factors for a worse disease-free survival and overall survival, whereas the HPV status was associated with a better overall survival (OR, 0.33; 95% CI, 0.13-0.81; p=0.01). Taken together these results indicate that distinct pathological mechanisms for the malignant transformation in each single HN subsite should be taken in account; HPV molecular analyses should be considered a valid tool to distinguish subsets of oropharyngeal tumours and HPV presence could be useful for the prognostic assessment of HNSCC. IntroductionTumours of the oral cavity and pharynx have been estimated at 643,000 cases for 2002, with 349,000 deaths (1). The incidence of these cancers is traditionally found to be very high in some areas of the world (e.g., France and South India), but in the last decade other areas (e.g., Eastern Europe and Japan) reported an increasing incidence of head and neck (HN) squamous cell carcinomas (SCC) (2). HN cancer constitutes one of the most difficult pathologies to eradicate. Recurrences are frequent and about a half of patients die (1). The heterogeneity of treatment response and the lack of prognostic factors could be the main causes of the adverse clinical outcome. Moreover, the behaviour variability of each individual tumour has also emphasized the difficulties of managing these tumours.Life habits such as the intake of toxic agents present in tobacco smoke, alcohol drink and betel chewing, or poor hygiene remain major risk factors for these tumours. However, the fraction of HN cancers attributable to these risk factors is close to 80-90%, while the...

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“…The deregulation of the p53 and pRb pathways in both HPV related andunrelated carcinogenic routes will ultimately result in a deregulation of the cell cycle and of the apoptotic process, finally leading to chromosome instability. 12,13 The occurrence of chromosome instability is considered to be a late event in HPV related carcinogenesis. In vitro studies with HPV-E6/E7 immortalized keratinocytes and raft cultures have shown that a persistent HPV infection is not sufficient for malignant transformation.…”

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confidence: 99%

Chromosome stability in tonsillar squamous cell carcinoma is associated with HPV16 integration and indicates a favorable prognosis

Mooren

Kremer

Claessen

et al. 2012

Intl Journal of Cancer

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Tonsillar squamous cell carcinoma (TSCC) is frequently associated with human papillomavirus (HPV) and chromosome instability. Data from cellular model systems are, however, controversial concerning a relation between HPV and chromosome instability development. Here we studied this association in 77 primary TSCC with known clinical outcome and cell cycle protein expression profiles. Thirty‐two tumors (42%) showed HPV16‐integration. All 77 cases were analyzed by fluorescence in situ hybridization using chromosome 1‐ and 7‐specific centromere DNA probes to detect chromosome instability, indicated by the presence of chromosome imbalances and/or polyploidization for these chromosomes. In addition, eight HPV‐positive dysplasias, seven of which were adjacent to a carcinoma, were analyzed. Disomy for chromosome 1 and 7 was present in 29 out of 77 TSCC (38%), of which 19 were HPV16‐positive (p = 0.002). Aneusomy was observed in the remaining 48 TSCC, of which 13 were HPV‐positive. Aneusomies correlated significantly with tobacco‐ and alcohol consumption (p = 0.001 and p = 0.016, respectively) and a higher T‐stage (p = 0.018). Both HPV‐positivity and chromosome disomy were significantly associated with a favorable disease‐free survival (p = 0.001 and p = 0.025, respectively). Particularly in the HPV16‐positive group chromosome instability is a very strong indicator for an unfavorable prognosis (p = 0.032). In the dysplasias an identical HPV and chromosome copy number status was identified as in the adjacent tumors. We conclude that HPV‐positive TSCC and their precursor lesions are more often genetically stable than HPV‐negative lesions and that these tumors are associated with a favorable prognosis. Chromosome instability is an indicator for unfavorable prognosis, particularly in the HPV‐positive patient group.

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Role of human papillomavirus in the development of head and neck squamous cell carcinomas

Cited by 80 publications

References 15 publications

Human Papillomavirus as an Independent Predictor in Oral Squamous Cell Cancer

Human Papillomavirus as an Independent Predictor in Oral Squamous Cell Cancer

Molecular analyses and prognostic relevance of HPV in head and neck tumours

Chromosome stability in tonsillar squamous cell carcinoma is associated with HPV16 integration and indicates a favorable prognosis

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