HPV is here to stay

Editorials

Guest Editorial

hpv is here to stay


Martin Corsten , MD

doi: http://dx.doi.org/10.3747/co.20.1569

Human papillomavirus ( hpv ) was first detected in head-and-neck cancers in the 1980s1. By 2001, Gillison and Shah—and others—had established clear evidence that hpv has a causal role in a significant subset of head-and-neck cancers2. Since then, it has become clear that hpv is associated primarily with oropharyngeal carcinomas, especially tonsillar cancers, and the proportion of oropharyngeal carcinomas considered to be associated with hpv has risen significantly3. Mounting evidence has also suggested that the cancers caused by hpv are substantially different in epidemiology, clinical behavior, response to treatment, and outcome than the typical smoking-related squamous-cell head-and-neck cancers treated previously. The hpv -related tumours, connected mostly to hpv -16 and -18, are seen in younger, healthier patients and usually in non-smokers4. They have dramatically better rates of response to chemoradiotherapy, and descriptions have emerged of substantially higher rates of disease-specific survival and overall survival in hpv -positive and p16-positive tumours5,6.

Data from the United States and Europe have shown a dramatic increase in the incidence of oropharyngeal cancers related to hpv since the early 2000s3,7. That increase has led some authors to describe an “epidemic” of such cancers8,9. It is commonly felt that changes in sexual mores and in oral sexual behavior are linked to this increased incidence10. That incidence trend—and the different biologic behavior of these tumours—has led to a number of critical changes in the way that physicians treat and study this disease.

First, to be valid, research into head-and-neck cancers now has to consider hpv status. Differences in outcome that might seem to be related to different treatments could simply represent a varying proportion of hpv cases in the different study arms. Noncontemporaneous evaluations of treatment—that is, a “novel” treatment compared with “historical controls”—are impossible when the percentage of hpv -positive cases has not been static over the past several decades.

Second, the markedly higher cure rates for hpv- related tumours, and thus oropharyngeal cases in particular, have resulted in a shift from a concentration on survival to a concentration on quality of life and toxicity. Discussions about de-escalation of treatment for hpv -positive cases are now commonplace, and alternative, potentially less toxic, therapies including targeted agents and robotic surgery are being evaluated. Third, the realization that hpv -positive and hpv- negative head-and-neck cancer are essentially two different disease entities is accelerating the concept of “personalized medicine” in head-and-neck cancer, in which tumour and patient characteristics will be used to define individualized treatment regimens.

Lastly, the realization that hpv infection is such an important causative agent in oropharyngeal cancer (in addition to cervical cancer) will have to inform the public health debate around vaccination programs, including the need for vaccinating men.

The paper by Nichols et al. 11 in this issue of Current Oncology provides direct evidence of the increase in tonsillar cancers, and in hpv -positive cancers in particular, in a large Canadian academic health sciences centre over two decades (1993–2011). Although the increase in oropharyngeal cancer in Canada has been reported using Canadian national cancer registry data12,13, population-based studies allow only for inferences about the influence of hpv on changes in incidence. Centres across Canada have now begun routine testing of head-and-neck cancers for hpv , but the paper by Nichols and colleagues provides case-by-case information about the contribution of hpv to the dramatic increase in the oropharyngeal cancer incidence seen in Canada since the early 1990s.

The Nichols paper has limitations, as the authors indicate in their discussion. Cases were collected from a pathology database, the dynamics of which may have changed over time, and despite being in the database, a small number of cases were excluded because of tissue unavailability. A large number of other tonsillar cancer cases were excluded because they were treated on the basis of fine-needle aspiration biopsy alone, or because the original biopsy was performed at a community hospital. Those cases represented fewer than 20% of the oropharyngeal cancer cases treated at the London Regional Cancer Program over the study period. Finally, the data come from a single institution and may reflect some inherent population-based characteristics in its region of southwest Ontario compared with Canada as a whole.

Despite those limitations, the paper makes an important contribution to the ongoing literature about hpv and head-and-neck cancer. It helps to confirm that the Canadian experience with hpv is similar to that seen in the United States and Europe, and it informs the debate on vaccination programs for hpv in Canada. Infections involving hpv have transformed the landscape of head-and-neck cancer and will continue to cause dramatic changes in the epidemiology, treatment, and prevention of this disease into the future.

CONFLICT OF INTEREST DISCLOSURES

The author has no financial conflicts of interest to disclose.

REFERENCES

1. Lindeberg H, Fey SJ, Ottosen PD, Mose Larsen P. Human papilloma virus (hpv) and carcinomas of the head and neck. Clin Otolaryngol Allied Sci 1988;13:447–54.
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2. Gillison ML, Shah KV. Human papillomavirus-associated head and neck squamous cell carcinoma: mounting evidence for an etiologic role for human papillomavirus in a subset of head and neck cancers. Curr Opin Oncol 2001;13:183–8.
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3. Chaturvedi AK, Engels EA, Pfeiffer RM, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol 2011;29:4294–301.
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4. Joseph AW, D’Souza G. Epidemiology of human papillomavirus– related head and neck cancer. Otolaryngol Clin North Am 2012;45:739–64.
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5. Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 2010;363:24–35.
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6. O’Rorke MA, Ellison MV, Murray LJ, Moran M, James J, Anderson LA. Human papillomavirus related head and neck cancer survival: a systematic review and meta-analysis. Oral Oncol 2012;48:1191–201.
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7. Blomberg M, Nielsen A, Munk C, Kjaer SK. Trends in head and neck cancer incidence in Denmark, 1978–2007: focus on human papillomavirus associated sites. Int J Cancer 2011;129:733–41.
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8. Marur S, D’Souza G, Westra WH, Forastiere AA. hpv-associated head and neck cancer: a virus-related cancer epidemic. Lancet Oncol 2010;11:781–9.
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9. Ramqvist T, Dalianis T. An epidemic of oropharyngeal squamous cell carcinoma (oscc) due to human papillomavirus (hpv) infection and aspects of treatment and prevention. Anticancer Res 2011;31:1515–19.
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10. D’Souza G, Agrawal Y, Halpern J, Bodison S, Gillison ML. Oral sexual behaviors associated with prevalent oral human papillomavirus infection. J Infect Dis 2009;199:1263–9.
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11. Nichols AC, Palma DA, Dhaliwal SS, et al. The epidemic of human papillomavirus and oropharyngeal cancer in a Canadian population. Curr Oncol 2013;20:212–219.
cross-ref  

12. Forte T, Niu J, Lockwood GA, Bryant HE. Incidence trends in head and neck cancers and human papillomavirus (hpv)–associated oropharyngeal cancer in Canada, 1992–2009. Cancer Causes Control 2012;23:1343–8.
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13. Johnson–Obaseki S, McDonald JT, Corsten M, Rourke R. Head and neck cancer in Canada: trends 1992 to 2007. Otolaryngol Head Neck Surg 2012;147:74–8.
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Correspondence to: Martin Corsten, S-3, 501 Smyth Road, Ottawa, Ontario K1H 8L6. E-mail: mcorsten@ottawahospital.on.ca

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Current Oncology , VOLUME 20 , NUMBER 4 , AUGUST 2013








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ISSN: 1198-0052 (Print) ISSN: 1718-7729 (Online)