Amanda-Louise Fenger Carlander1, Christian Grønhøj Larsen1, David Hebbelstrup Jensen1, Emilie Garnæs1, Katalin Kiss2, Luise Andersen2, Caroline Holkmann Olsen3, Maria Franzmann4, Estrid Høgdall5, Susanne K Kjær6, Bodil Norrild7, Lena Specht8, Elo Andersen9, Thomas van Overeem Hansen10, Finn Cilius Nielsen10, Christian von Buchwald11. 1. Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen Oe, Denmark. 2. Department of Pathology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen Oe, Denmark. 3. Department of Pathology, Roskilde Sygehus, Sygehusvej 9, 4000 Roskilde, Denmark. 4. Department of Pathology, Hvidovre Hospital, Kettegaard Alle 30, 2650 Hvidovre, Denmark. 5. Department of Pathology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev Ringvej 75, 2730 Herlev, Denmark. 6. Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Strandboulevarden 49, 2100 Copenhagen Oe, Denmark; Department of Gynaecology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen Oe, Denmark. 7. Institute of Cellular and Molecular Medicine, Panum Institute, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark. 8. Department of Oncology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen Oe, Denmark. 9. Department of Oncology, Herlev Hospital, Herlev Ringvej 75, 2730 Herlev, Denmark. 10. Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen Oe, Denmark. 11. Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen Oe, Denmark. Electronic address: Christian.von.buchwald@regionh.dk.
Abstract
BACKGROUND: Human papillomavirus (HPV) is a critical element in the rising incidence of oropharyngeal squamous cell carcinoma (OPSCC), although whether this trend will continue, and the types of HPV responsible, are currently unknown. We previously demonstrated an increased incidence of HPV-related OPSCC in the high HPV prevalence area of Eastern Denmark from 2000 to 2010. Therefore, we investigated if the incidence for OPSCC continued to rise, the association to HPV and putative HPV-types in Eastern Denmark from 2011 to 14. We then projected the expected incidence of OPSCC versus cervical cancer through to 2020. PATIENTS AND METHODS: Patients with OPSCC (tonsillar squamous cell carcinoma [TSCC] and base of tongue squamous cell carcinoma [BSCC]) were identified via the Danish Head and Neck Cancer Group and the Danish Pathology Databank (n = 700). Tumours were re-reviewed and assessed using p16 immunohistochemistry, HPV DNA polymerase chain reaction (PCR), with genotyping by next generation sequencing. RESULTS: Sixty-two percent (432/700) of tumours were HPV-positive (HPV+). The total incidence rate (per 100.000) for OPSCC increased from 4.0 in 2011 to 4.5 in 2014, primarily due to a rise in HPV+ TSCCs and HPV+ BSCCs, although numbers of HPV-negative (HPV-) OPSCC also increased during the study period. The majority of HPV+ tumours were HPV16 DNA positive (86%), but we also identified HPV33 DNA (6%), HPV35 DNA (4%) and others (3%), including HPV18, 26, 31, 45, 56, 58, 59 and HPV67. CONCLUSION: An increasing incidence of OPSCC is driven primarily by HPV+ OPSCC. Sixty-two percent of tumours were HPV+, which is a high-prevalence, although the lower number of HPV- cases has yet to stabilise. HPV16 was the predominant genotype, although a significant proportion (14%) was of another genotype. Our projections suggest that the number of HPV+ OPSCC will exceed that of cervical cancer in 2016 in Eastern Denmark.
BACKGROUND:Human papillomavirus (HPV) is a critical element in the rising incidence of oropharyngeal squamous cell carcinoma (OPSCC), although whether this trend will continue, and the types of HPV responsible, are currently unknown. We previously demonstrated an increased incidence of HPV-related OPSCC in the high HPV prevalence area of Eastern Denmark from 2000 to 2010. Therefore, we investigated if the incidence for OPSCC continued to rise, the association to HPV and putative HPV-types in Eastern Denmark from 2011 to 14. We then projected the expected incidence of OPSCC versus cervical cancer through to 2020. PATIENTS AND METHODS: Patients with OPSCC (tonsillar squamous cell carcinoma [TSCC] and base of tongue squamous cell carcinoma [BSCC]) were identified via the Danish Head and Neck Cancer Group and the Danish Pathology Databank (n = 700). Tumours were re-reviewed and assessed using p16 immunohistochemistry, HPV DNA polymerase chain reaction (PCR), with genotyping by next generation sequencing. RESULTS: Sixty-two percent (432/700) of tumours were HPV-positive (HPV+). The total incidence rate (per 100.000) for OPSCC increased from 4.0 in 2011 to 4.5 in 2014, primarily due to a rise in HPV+ TSCCs and HPV+ BSCCs, although numbers of HPV-negative (HPV-) OPSCC also increased during the study period. The majority of HPV+ tumours were HPV16 DNA positive (86%), but we also identified HPV33 DNA (6%), HPV35 DNA (4%) and others (3%), including HPV18, 26, 31, 45, 56, 58, 59 and HPV67. CONCLUSION: An increasing incidence of OPSCC is driven primarily by HPV+ OPSCC. Sixty-two percent of tumours were HPV+, which is a high-prevalence, although the lower number of HPV- cases has yet to stabilise. HPV16 was the predominant genotype, although a significant proportion (14%) was of another genotype. Our projections suggest that the number of HPV+ OPSCC will exceed that of cervical cancer in 2016 in Eastern Denmark.
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