Re: Cervical Carcinoma and Human Papillomavirus: On the Road to Preventing a Major Human Cancer (original) (raw)

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_Correspondence to:_F. Xavier Bosch, M.D., Institut Català d'Oncologia, Servei de'Epidemiologia i Registre del Càncer, Av. Gran Via s/n, Km. 2.7, E-08907 L'Hospitalet de Llobregat, Barcelona, Spain (e-mail: x.bosch@ico.scs.es).

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Published:

05 September 2001

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F. Xavier Bosch, Nubia Muñoz, Silvia de Sanjosé, Eduardo L. F. Franco, Douglas R. Lowy, Mark Schiffman, Silvia Franceschi, Susanne Krüger Kjaer, Chris J. L. M. Meijer, Ian H. Frazer, Jack Cuzick, Re: Cervical Carcinoma and Human Papillomavirus: On the Road to Preventing a Major Human Cancer, JNCI: Journal of the National Cancer Institute, Volume 93, Issue 17, 5 September 2001, Pages 1349–1350, https://doi.org/10.1093/jnci/93.17.1349
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In an editorial in the February 21, 2001, issue of the Journal, H. zur Hausen (1) reviewed historical aspects of the field of human papillomaviruses (HPVs) and cervical cancer. In his final remarks, he described an unjustified delay in HPV vaccine development by industrial partners. In his view, this delay was related to the cautious interpretation of the early results that was taken by epidemiologists at the International Agency for Research on Cancer (IARC) and elsewhere. Some of the implications of the editorial are in our view too negative.

HPV research has benefited from a remarkable collaboration between epidemiologists and basic scientists. Given the right biomarkers and testing systems, in slightly more than a decade, it has been possible to demonstrate a strong, specific, and universal association between HPV infection and risk of human cervical cancer. Studies based on populations are the only ones capable of estimating the natural history parameters that are essential to plan, conduct, and evaluate preventive strategies. These strategies refer equally to the fundamental and rapidly growing field of HPV-based screening programs (2) as well as to HPV vaccination trials.

The time lag that was required to characterize the association can be largely traced to the limitations of the early HPV-DNA tests. Some of the well-designed epidemiologic studies carried out during the late 1980s provided inconsistent evidence because of the use of assays with low specificity and sensitivity (3,4). Progress in HPV detection systems has been remarkable and, by the late 1990s, HPV was proposed as the first “necessary, non-sufficient” cause of a human cancer ever identified (5). In 1992 and 1995, respectively, one scientific publication (6) and a monograph (7) produced by the IARC, with an international participation of close to 60 external scientists, reviewed the field and considered HPV16 and HPV18 to be human carcinogens.

The inference that the biotechnology industry was reluctant to invest in HPV vaccine development largely because of IARC's cautious views in the late 1980s gives undue weight to this single element. Academic arguments are one (albeit necessary) component of a complex decision-making process. Market considerations aside, identifying the appropriate technologies was probably also a strong determinant of industrial decisions. As noted in the editorial (1), the virus-like particle technology that is used both as the basis for most candidate vaccines and as a way to measure immune response to vaccination was not in place until the early 1990s, just after the development of validated HPV detection systems required for clinical vaccination trials.

The biomedical literature has many examples of false starts in carcinogen discoveries. Rather than delaying progress in the field, epidemiologists have kept a fast research pace, providing the evidence required and implementing novel preventive efforts. In the immediate future, collaboration across disciplines will have an increasing relevance. Highly sophisticated technologies are already being proposed for population screening and individual diagnosis. In this bright perspective, mutual contributions and expertise are more necessary than ever.

In conclusion, we certainly share Professor zur Hausen's view that HPV is the eminently preventable cause of cervical cancer, but in the late 1980s it seemed prudent to many to wait until consistent epidemiologic data supported the inferences from molecular biologic studies.

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Munoz N, Bosch FX, Shah KV, Meheus A, editors. The epidemiology of human papillomavirus and cervical cancer. Lyon (France): International Agency for Research on Cancer. IARC Sci Publ No. 119;1992.

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IARC Working Group. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: human papillomavirus. Lyon (France): International Agency for Research on Cancer. IARC Sci Publ Vol 64;1995.

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