Human papillomavirus DNA and p16INK4a expression in hypopharyngeal cancer and in relation to clinical outcome, in Stockholm, Sweden

Dalianis, Tina; Grün, Nathalie; Koch, J.; Vlastos, Andrea; Tertipis, Nikolaos; Nordfors, Cecilia; Näsman, Anders; Wendt, Malin; Romanitan, Mircea; Bersani, Cinzia; Munck‐Wikland, Eva; Ramqvist, Torbjörn

doi:10.1016/j.oraloncology.2015.06.002

Cited by 35 publications

(58 citation statements)

References 22 publications

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“…The prevalence of HPV16 had not increased and was 3.7% (22). Notably, among the 142 patients diagnosed in 2000-2011 with hypopharyngeal cancer in Stockholm, Sweden, the ones with tumours that were HPV16 DNA-positive and overexpressed p16, had a significantly better 3-year OS (P=0.0185) compared with others (22). In addition, a similar tendency was observed for disease-specific survival (DSS) (P= 0.0581).…”

Section: Hpv In Hypopharyngeal Cancermentioning

confidence: 83%

“…In the same study, p16 overexpression was observed in 14% of the hypopharyngeal cancer cases, and was not found to be a suitable surrogate marker for the presence of HPV DNA; furthermore, it was not correlated with survival (20). This study was later followed up to determine whether the proportion of HPV-positive tumours had increased in the Stockholm region during the years 2008-2013, and whether the combined presence of HPV16 DNA and p16 overexpression was correlated with survival (22). The prevalence of HPV16 had not increased and was 3.7% (22).…”

Section: Hpv In Hypopharyngeal Cancermentioning

confidence: 99%

“…This study was later followed up to determine whether the proportion of HPV-positive tumours had increased in the Stockholm region during the years 2008-2013, and whether the combined presence of HPV16 DNA and p16 overexpression was correlated with survival (22). The prevalence of HPV16 had not increased and was 3.7% (22). Notably, among the 142 patients diagnosed in 2000-2011 with hypopharyngeal cancer in Stockholm, Sweden, the ones with tumours that were HPV16 DNA-positive and overexpressed p16, had a significantly better 3-year OS (P=0.0185) compared with others (22).…”

Section: Hpv In Hypopharyngeal Cancermentioning

confidence: 99%

“…Accumulating reports describe the presence of HPV DNA in several cancers of unknown primary (CUP) in the head and neck region, as well as in a minority of hypopharyngeal cancers and other non-OPSCC locations (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). Notably, patients with HPV-positive tumours, particularly in CUP of the head and neck region and possibly also in hypopharyngeal cancer, tend to have a better clinical outcome compared with those with corresponding HPV-negative tumours, in whom HPV status may also have implications for diagnosis and therapy (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)27,28). However, this has not been investigated in the same detail for other cancer locations in the head and neck region, whereas reports usually compare survival between patients with HPV-positive and those with HPV-negative non-OPSCC.…”

Section: Introductionmentioning

confidence: 99%

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Human papillomavirus is a favourable prognostic factor in cancer of unknown primary in the head and neck region and in hypopharyngeal cancer

Sivars¹,

Bersani²,

Grün³

et al. 2016

Molecular and Clinical Oncology

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Abstract. Human papillomavirus (HPV), in addition to smoking and alcohol, is a cause of oropharyngeal squamous cell carcinoma (OPSCC), particularly of the tonsils and base of the tongue (TSCC and BOTSCC, respectively). Moreover, HPV-positive TSCC and BOTSCC are associated with a better outcome compared with their HPV-negative counterparts (80 vs. 40% 3-year disease-free survival rate, respectively) and their incidence has increased in several countries. Recently, accumulating evidence of HPV in a considerable proportion of cancers of unknown primary (CUP) in the head and neck region and in a small proportion of hypopharyngeal SCCs has been reported. Furthermore, HPV-positive tumours, particularly cases with HPV DNA positivity in combination with overexpression of p16, also tend to have a better clinical outcome compared with that of the corresponding HPV-negative tumours. This finding is particularly prominent in HPV-positive CUPs of the head and neck region, where the primary tumour likely originates from the oropharynx. Thus, the determination of HPV status and p16 expression may be of value for the diagnosis and treatment of CUP of the head and neck region and may also be of value for hypopharyngeal cancers in the future. However, for hypopharyngeal cancer as well as other non-OPSCCs, additional studies per subsite on the effect of HPV status on survival are required.

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Section: Hpv In Hypopharyngeal Cancermentioning

confidence: 83%

Section: Hpv In Hypopharyngeal Cancermentioning

confidence: 99%

Section: Hpv In Hypopharyngeal Cancermentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Human papillomavirus is a favourable prognostic factor in cancer of unknown primary in the head and neck region and in hypopharyngeal cancer

Sivars¹,

Bersani²,

Grün³

et al. 2016

Molecular and Clinical Oncology

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“…IHC evaluations were conducted as described previously (11,18,20). For detection of p16 INK4A , Ventana CINtec ® p16 Histology (Roche AB, Stockholm, Sweden) was used and samples were considered positive if >70% of tumour cells showed strong staining (6,23).…”

Section: Methodsmentioning

confidence: 99%

Validation of Human Papillomavirus as a Favourable Prognostic Marker and Analysis of CD8+ Tumour-infiltrating Lymphocytes and Other Biomarkers in Cancer of Unknown Primary in the Head and Neck Region

Sivars¹,

Landin²,

Grün³

et al. 2017

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Abstract. Background: Human papillomavirus (HPV) is a favourable prognostic factor in oropharyngeal cancer. Moreover, we and others reported that HPV-positive cancer of unknown primary in the head and neck region (HNCUP) has better outcome than HPVHead and neck squamous cell carcinoma (HNSCC), including cancer of the pharynx, larynx, oral cavity, nose and nasal sinuses, often presents as a lump in the neck, and the specific site of the primary tumour is in general revealed after subsequent diagnostic procedures. However, in 2-9% of the cases the primary tumour is not found and the condition is denoted as cancer of unknown primary in the head and neck region (HNCUP) (1). Treatment of the latter has traditionally comprised of neck dissection followed by postoperative oncological treatment, i.e. radiotherapy, at times with the addition of platinum-based chemotherapy or cetuximab, while today in some cases only oncological treatment is given (2).Human papillomavirus (HPV)-associated oropharyngeal SCC is a HNSCC subset dominated by tonsillar and base of tongue SCC (3, 4). HPV-positive tonsillar and base of tongue SCC have increased in incidence in the past decades in the developed world and have better clinical outcomes than HNSCC in general [~80% vs. 40% 5-year overall survival (OS)] (5-8). HPV is frequently found in HNCUP and such cases likely have an HPV-positive oropharyngeal SCC origin, which gives reasons for steering diagnostic procedures as well as radiotherapy towards the oropharynx (9-11).Treatment de-escalation may be attainable in patients with HPV-positive HNCUP, similar to that discussed for patients with HPV-positive oropharyngeal SCC (12). Still, before HPV status of HNCUP can be used to guide treatment, more knowledge on the biology and clinical behaviour of the 665 Τhis article is freely accessible online.

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Detection of human papillomavirus type 16 in oropharyngeal squamous cell carcinoma using droplet digital polymerase chain reaction

Biron

Kostiuk

Isaac

et al. 2016

Cancer

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BACKGROUND:The incidence of oropharyngeal squamous cell carcinoma caused by oncogenic HPV (HPV-OPSCC) is rising worldwide. HPV-OPSCC is commonly diagnosed by RT-qPCR of HPV-16 E6 and E7 oncoproteins or by cyclin-dependent kinase inhibitor 2A, multiple tumor suppressor 1 (p16) immunohistochemistry (IHC). Droplet digital PCR (ddPCR) has been recently reported as ultrasensitive and highly precise method of nucleic acid quantification for biomarker analysis. We aimed to validate this method for the detection of HPV-16 E6 and E7 in HPV-OPSCC. METHODS: Participants were recruited from January 2015-November 2015 at initial presentation to the University of Alberta Head and Neck Oncology Clinic. RNA was extracted, purified and quantified from prospectively collected participant tissues, and ddPCR was performed with fluorescent probes detecting HPV-16 E6 and E7. Results from ddPCR were compared with p16 IHC performed by clinical pathology as standard of care. RESULTS: Head and neck tissues were prospectively obtained from 68 participants including 29 patients with OPSCC, 29 patients with non-OPSCC and 10 patients without carcinoma. 79.2% of patients with OPSCC were p16 positive. The sensitivity and specificity of ddPCR HPV E6/E7 compared with p16 IHC in OPSCC was 91.3 and 100%, respectively. The amount of target RNA used was 1 ng, 20-50 times lower than reported by other for RT-qPCR HPV E6/E7. CONCLUSIONS: The ddPCR of HPV E6/E7 is a novel and highly specific method of detecting HPV-16 in OPSCC.

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Human papillomavirus DNA and p16INK4a expression in hypopharyngeal cancer and in relation to clinical outcome, in Stockholm, Sweden

Cited by 35 publications

References 22 publications

Human papillomavirus is a favourable prognostic factor in cancer of unknown primary in the head and neck region and in hypopharyngeal cancer

Human papillomavirus is a favourable prognostic factor in cancer of unknown primary in the head and neck region and in hypopharyngeal cancer

Validation of Human Papillomavirus as a Favourable Prognostic Marker and Analysis of CD8+ Tumour-infiltrating Lymphocytes and Other Biomarkers in Cancer of Unknown Primary in the Head and Neck Region

Detection of human papillomavirus type 16 in oropharyngeal squamous cell carcinoma using droplet digital polymerase chain reaction

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