HPV and Oropharyngeal Cancer
HPV-associated Oropharyngeal squamous cell cancer has one of the most rapidly rising incidences of any cancer in high income countries, having overtaken the rates of cervical cancer in the UK.
Although still a rare cancer, HPV-associated oropharyngeal squamous cell cancer (OPSCC) has one of the most rapidly rising incidences of any cancer in high income countries, having overtaken cervical cancer in the UK (M. Lechner, et al. Nature Reviews of Clinical Oncology. 2022 and M. Lechner, et al. Lancet Infect. Dis. 2019; 19: 131-132) and in the US.
The increasing rates of HPV-positive OPSC will have a tremendous healthcare cost, with estimated overall cost for treatment in the UK amounting to £2 billion over the next twenty years (in men only). Taking into account broader societal costs, we estimate that HPV-positive OPSCC will cost the UK more than £18 billion over the next twenty years (M. Lechner et al.; Lancet. 2019; 393: 2123). A similar study is currently conducted for the US (M. Lechner et al).
HPV-positive OPSCC is distinct from its HPV-negative counterpart, which is largely caused by tobacco use and predominantly affects older men. In contrast, HPV-positive OPSCC is caused by oncogenic HPV infection and tends to impact younger men, with a distinct and unique molecular profile. Importantly, HPV positivity confers an improved prognosis.
However, positive clinical outcome is hindered by a lack of effective prevention and early detection measures, which is exacerbated by low awareness of the link between HPV infection and OPSCC, particularly in men. Of 1,200 respondents in a UK-wide, population-based survey (649 [54.1%] female), only 444 (37.0%; 95% CI 34.3–39.7) had ever heard of HPV. Of these, 309 (69.6%; 65.2–73.7) knew that HPV could be transmitted during sex, 172 (38.7%; 34.3–43.3) recognized HPV as a risk factor for oropharyngeal squamous cell cancer, and 283 (63.7%; 59.2–68.1) knew that a preventive vaccine existed. Women were almost twice as likely to be aware of HPV as were men (290 [44.7%] vs 154 [27.9%]; p<0.001) (M. Lechner et al.; Lancet Infectious Diseases. 2019; 19(2):131-132).
This is important as OPSCC is often detected at a late stage, which directly impacts clinical outcome and survival. Improving public awareness of the cancer risk as well as educating individuals on symptoms would not only reduce the incidence but also aid in earlier detection. Importantly, Primary care physicians (GPs) are at the nexus of the general public and our healthcare systems and have the ability to promote public health initiatives. In survey across primary care physicians, we found that while 74% of primary care physicians recognised HPV as a risk factor for OPSCC, less than half were aware that being male was a risk factor for HPV-associated OPSCC (M. Lechner, et al. BMJ Open. 2018; 8: e023339).
HPV-positive OPSCC is treated in much the same way as HPV-negative disease and centres on surgery and chemoradiotherapy. There are ongoing efforts to de-escalate treatment due to the high incidence of treatment-related adverse events and reduced post-treatment quality of life. However, there is much need for an improved understanding of the molecular profile of these tumours as well as the identification of clinically important risk factors in order to properly stratify patients and allocate treatment accordingly. This will further add to the identification of therapeutic targets and the development of precision medicine, including the paramount task of identifying biomarkers for early detection.
HPV Awareness
Project Lead: Lau Zi Jian (Shawn) (Research Fellow)
HPV-associated oropharyngeal squamous cell cancer (OPSCC) has one of the most rapidly rising incidences of any cancer in high income countries, having overtaken cervical cancer in the UK.
(M. Lechner, et al. Lancet Infect. Dis. 2019; 19: 131-132.)
Novel treatment approaches for HPV-associated Oropharyngeal Cancer (HPV-PROTAC project)
Project lead: Yujia Liu (PhD student)
In collaboration with other UCL researchers we are currently developing novel agents to target HPV viral proteins via the Interdisciplinary programme for PROTAC development for virally-induced head and neck cancers (David Selwood, Rob Sellar, David Shorthouse, Matt Lechner).
1. HPV-associated Oropharyngeal Cancer; M. Lechner et al.; Nature Reviews of Clinical Oncology. 2022 ; 19(5):306-327. doi: 10.1038/s41571-022-00603-7. Epub 2022 Feb PMID: 35105976; PMCID: PMC8805140.
2. S. Basyuni …, M. Lechner, … A. Schache. Value of p53 sequencing in the prognostication of head and neck cancer: a systematic review and meta-analysis. Scientific Reports. 2022. 1;12(1):20776. doi: 10.1038/s41598-022-25291-2.
3. A. Chakravarthy …, M. Lechner, …, T.R. Fenton. Integrated analysis of cervical squamous cell carcinoma cohorts from three continents reveals conserved subtypes of prognostic significance. Nature Communications. 2022;13(1):5818. doi: 10.1038/s41467-022-33544-x.
4. Awareness of Human Papillomavirus (HPV) and HPV Vaccination amongst the General Population in Germany: Lack of Awareness and Need for Action. S.J. Sharma, ... , M. Lechner, U. Wieland, J.P. Klussmann. Oncol Res Treat. 2022; 45(10):561-567. doi: 10.1159/000525697.
5. Reply to 'HPV-associated oropharyngeal cancer - discussion points'. Lechner M, Liu J, Masterson L, Fenton TR. Nature Reviews of Clinical Oncology. 2022 Jun;19(6):422-423. doi: 10.1038/s41571-022-00627-z. PMID: 35351994.
6. Public awareness of the association between human papillomavirus and oropharyngeal cancer. F. Verhees, I. Demers, L.J. Schouten, M. Lechner, E.M. Speel, B. Kremer. Eur J Public Health. 2021 Oct 26;31(5):1021-1025. doi: 10.1093/eurpub/ckab081. PMID: 34233355; PMCID: PMC8565482.Targeting key groups using a low-cost strategy to increase HPV awareness and vaccine uptake. O. Jones, C. Vassie, O. Emanuel & M. Lechner; Vaccine. 2020; 38(25):4059. doi:10.1016/j.vaccine.2020.02.022
7. Early detection strategies urgently needed to limit HPV-associated OPSCC morbidity, mortality and cost. M. Lechner et al.; Lancet. 2019; 393(10186):2123.
8. Gender-neutral HPV vaccination in the UK, rising male oropharyngeal cancer rates, and lack of HPV awareness. M. Lechner et al.; Lancet Infectious Diseases. 2019; 19(2):131-132.
9. A Cross-Sectional Survey of Awareness of Human Papillomavirus-associated Oropharyngeal Cancers among General Practitioners in the UK. M. Lechner, et al.; BMJ Open. 2018; 8(7): e023339
10. Pan-cancer deconvolution of tumour composition using DNA methylation. A. Chakravarthy, A. Furness, K. Joshi, E. Ghorani, K. Ford, M.J. Ward, E.V. King, M. Lechner, T. Marafioti, S.A. Quezada, G.J. Thomas, A. Feber, T.R. Fenton. Nature Communications. 2018; 13;9(1): 3220.
11. Frequent HPV-independent p16/INK4A overexpression in head and neck cancer. M. Lechner, A.R. Chakravarthya, V. Walter, L. Masterson, A. Feber, A. Jay, P.M. Weinberger, R. McIndoe, C.T. Forde, K. Chester, N. Kalavrezos, P. O'Flynn, M. Forster, T.M. Jones, F. Vaz, N. Hayes, T.R. Fenton; Oral Oncology. 2018; 83: 32-37
12. Until eradication, awareness. O.S. Jones, C. Vassie, R. Gilson, M. Lechner; Lancet Infectious Diseases. 2017, 17(4): 368-369
13. Expanding the benefits of HPV vaccination to boys and men. L. Masterson, J. O'Mahony, M. Lechner; Lancet. 2017, 388(10063):2992
14. Human papillomavirus drives tumor development throughout the head and neck: Improved prognosis is associated with an immune response largely restricted to the oropharynx. A. Chakravarthy, S. Henderson, S.M. Thirdborough, C.H. Ottensmeier, X. Su, M. Lechner, A. Feber, G.J. Thomas, T. Fenton; Journal of Clinical Oncology. 2016, 34(34):4132-4141
15. The Genomics, Epigenomics, and Transcriptomics of HPV-Associated Oropharyngeal Cancer - Understanding the Basis of a Rapidly Evolving Disease. M. Lechner et T. Fenton; Advances in Genetics; 2016, 93: 1-56.
16. CD8+ T cell response to human papillomavirus 16 E7 is able to predict survival outcome in oropharyngeal cancer. L. Masterson, M. Lechner, S. Loewenbein, H. Mohammed, C. Davies-Husband, T. Fenton, H. Sudhoff, P. Jani, P. Goon, J. Sterling; European Journal of Cancer. 2016, 67:141-151.
17. Health policy: HPV vaccination in boys - will the UK join the fight? L. Masterson and M. Lechner; Nature Reviews of Clinical Oncology. 2016, 13(12):721-722
18. Deregulation of SYCP2 predicts early stage HPV+ oropharyngeal carcinoma – a prospective whole transcriptome analysis. L. Masterson, F. Sorgeloos, D. Winder, M. Lechner, A. Marker, S. Malhotra, H. Sudhoff, P. Jani, P. Goon, J. Sterling; Cancer Science; 2015, 106(11):1568-75.
19. Exploring the implications of HPV infection for head and neck cancer; N. Field & M. Lechner; Sexually Transmitted Infections; 2015, 91(4):229-30.
20. Epigenetics markers of metastasis and HPV-induced tumorigenesis in penile cancer; A. Feber, M. Arya, P. De Winter, M. Saqip, R. Nigam, P. Malone, W.S. Tan, S. Rodney, M. Lechner, A. Freeman, C. Jameson, A. Muneer, S. Beck, J.D. Kelly; Clinical Cancer Research, 2015, 21(5):1196-206
21. Using high-density DNA methylation arrays to profile copy number alterations; A. Feber, P. Guilhamon, M. Lechner, T. Fenton, G.A. Wilson, C. Thirlwell, A.M. Flanagan, A.E. Teschendorff, J.D. Kelly, S. Beck; Genome Biology. 2014, 15(2): R30
22. Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing; G.M. Frampton, A. Fichtenholt, G.A. Otto, K. Wang, S.R. Downing, J. He, M. Schnall-Levin, J. White, E.M. Sanford, P. An, J. Sun, F. Juhn, K. Brennan, K. Iwanik, A. Maillet, J. Buell, E. White, M. Zhao, S. Balasubramanian, S. Terzic, T. Richards, V. Banning, L. Garcia, K. Mahoney, Z. Zwirko, A. Donahue, H. Beltran, J.M. Mosquera, M.A. Rubin, S. Dogan, C.V. Hedvat, M.F. Berger, L. Pusztai, M. Lechner, C. Boshoff, M. Jarosz, C. Vietz, A. Parker, V.A. Miller, J.S. Ross, J. Curran, M.T. Cronin, P.J. Stephens, D. Lipson, R. Yelensky; Nature Biotechnology. 2013, 10.1038/nbt.2696.
23. Integrated virus-host methylome analysis in head and neck squamous cell carcinoma; G.A. Wilson & M. Lechner, A. Koeferle, H. Caren, L.M. Butcher, A. Feber, T. Fenton, A. Jay, C. Boshoff, S. Beck; Epigenetics. 2013, 18:8(9).
24. Targeted Next-generation Sequencing of Head and Neck Squamous Cell Carcinoma identifies novel genetic alterations in HPV+ and HPV- tumours. M. Lechner, G. Frampton, T. Fenton, A. Feber, G. Palmer, A. Jay, N. Pillay, M. Forster, M.T. Cronin, D. Lipson, V.A. Miller, T.A. Brennan, S. Henderson, F. Vaz, P. O'Flynn, N. Kalavrezos, R. Yelensky, S. Beck, P.J. Stephens, C. Boshoff; Genome Medicine. 2013, 5(5): 49.
25. Identification and Functional Validation of HPV-mediated Hypermethylation in Head and Neck Squamous Cell Carcinoma. M. Lechner, T. Fenton, J. West, G. Wilson, A. Feber, S. Henderson, C. Thirlwell, H.K. Dibra, A. Jay, L. Butcher, A.R. Chakravarthy, F. Gratrix, N. Patel, F. Vaz, P. O'Flynn, N. Kalavrezos, A.E. Teschendorff, C. Boshoff, S. Beck; Genome Medicine. 2013, 5(2): 15.
26. One-stop Triple-Imaging: The way forward in Head and Neck Cancer management? P. Randhawa, J. Jie, M. Lechner, J. Rimmer, T. Beale, S. Morley, F. Vaz; Bulletin of The Royal College of Surgeons of England. 2013, 95(5): 1-4.
27. A Beta-Mixture Quantile Normalisation method for correcting probe design bias in Illumina Infinium 450k DNA methylation data. A.E. Teschendorff, F. Marabita, M. Lechner, T. Bartlett, J. Tegner, D. Gomez-Cabrero and S. Beck; Bioinformatics. 2013, 29(2): 189-96.
28. Comments on: Interpretation of genome-wide infinium methylation data from ligated DNA in formalin-fixed paraffin-embedded paired tumor and normal tissue. C. Thirlwell, A. Feber, M. Lechner, A.E. Teschendorff, S. Beck; BMC Research Notes. 2012, 13(5): 631.
29. Genome-wide DNA methylation analysis of archival formalin-fixed paraffin-embedded tissue using the Illumina Infinium HumanMethylation27 BeadChip. C. Thirlwell, M. Eymard, A. Feber, A.E. Teschendorff, K. Pearce, M. Lechner, M. Widschwendter, S. Beck; Methods. 2010, 52(3):248-54.
30. Cancer Epigenome. M. Lechner, C. Boshoff, S. Beck; Advances in Genetics. 2010, Vol. 70, Chapter 9; pages 247-276.
31. Cancer of the Nasopharynx. M. Chua, M. Lechner, B. Ma; Cancer: Principles & Practice of Oncology (12th edition)
32. Somatostatin receptor 2 expression in nasopharyngeal cancer is induced by Epstein Barr virus infection: impact on prognosis, imaging and therapy. M. Lechner, et al.; Nature Communications. 2020; 12(1):117. doi: 10.1038/s41467-020-20308-8.
33. SSTR2 in Nasopharyngeal Carcinoma: Relationship with Latent EBV Infection and Potential as a Therapeutic Target. O. Emanuel, J. Liu, V.H. Schartinger, W.L. Nei, Y.Y. Chan, C.M. Tsang, H. Riechelmann, L. Masterson, J. Haybaeck, U. Oppermann, S.M. Willems, M.L. Ooft, G. Wollmann, D. Howard, B. Vanhaesebroeck, V.J. Lund, G. Royle, M.L.K. Chua, K.W. Lo, P. Busson, and M. Lechner; Cancers. 2021; 13(19), 4944; https://doi.org/10.3390/cancers13194944
34. Clinical Outcomes, Kadish-INSICA Staging and Therapeutic Targeting of SSTR2 in Olfactory Neuroblastoma. M. Lechner, et al.; European Journal of Cancer. 2022; 162:221-236; doi: 10.1016/j.ejca.2021.09.046.
