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Dr. Nubia Muñoz

Dr. Nubia Munoz

The situation in the late 80’s was characterized by much scepticism concerning the role of HPV infection. Early molecular epidemiologic studies that attempted to test Zur Hausen’s hypothesis failed because they used the wrong tools for exposure assessment (i.e., HPV detection). Pharmaceutical companies were not interested in taking risks in pursuing the enormous expenditures (hundreds of millions of dollars are not uncommon as research and development costs to bring a new vaccine to the market) required to develop a vaccine that could prevent infection by a virus whose causal link with an important disease was not conclusively proven 1. From her unit at the International Agency for Research on Cancer (IARC), in Lyon, Muñoz began to lead in 1988 a massive effort that achieved two major goals, as described below.

First, she conducted an international series of case-control studies using modern laboratory techniques that ended up demonstrating that HPV infection by certain genotypes of HPV is unequivocally one of the strongest cancer risk factors ever found 23Her subsequent work also produced precise estimates of relative risks that permitted defining the HPV genotypes that had to be targeted for prevention 4. Likewise, it was from this enormous and persuasive series of case-control studies and from collaborative work that she had led as part of the International Biological Study of Cervical Cancer (IBSCC) that came the realization that HPV infection was not only the unequivocal central cause of cervical cancer but it should also be viewed as a necessary one 5. No other cancer prevention paradigms (e.g., smoking-lung cancer, HBV-liver cancer) have this distinction 6.

Secondly, she convinced the IARC to convene a group of experts to reach a consensus concerning the classification of HPVs as carcinogens for its authoritative Monograph series on carcinogenicity evaluation. In 1995, experts led by Muñoz classified HPVs 16 and 18 as two genotypes receiving the label “Group 1, Human Carcinogens” 7. This monograph had an enormous impact in subsequent prevention research and policy. The biotechnology industry began to develop HPV tests with the aim of improving traditional cervical cancer screening with Pap cytology to make it more efficient and more in line with the new knowledge. This led to today’s improved secondary prevention approaches in cervical cancer control via screening and management with HPV tests. Likewise, and more importantly, the 1995 IARC Monograph 8 gave pharmaceutical companies the body of evidence they needed to take the financial risks in developing and field-testing candidate HPV vaccines. The end result is that about 10 years later we have two new exciting fronts for cervical cancer prevention: HPV vaccination and improved screening with HPV tests, all originated from Muñoz’ vigorous and relentless leadership on the epidemiology front grounded on the pioneer work by Zur Hausen. It should be mentioned also that Muñoz, after retiring from the IARC, continued to influence the field by advising the vaccine companies to conduct relevant vaccination trials that could be generalizable worldwide.

References

  1. McIntyre P. Finding the viral link: the story of Harald zur Hausen. Cancer World July-August 2005: 32-37.
  2. Muñoz N, Bosch FX, de Sanjose S, Tafur L, Izarzugaza I, Gili M, Viladiu P, Navarro C, Martos C, Ascunce N, et al. The causal link between human papillomavirus and invasive cervical cancer: a population-based case-control study in Colombia and Spain. Int J Cancer. 1992 Nov 11;52(5):743-9.
  3. Muñoz N, Bosch FX, de Sanjose S, Herrero R, Castellsague X, Shah KV, Snijders PJ, Meijer CJ; International Agency for Research on Cancer Multicenter Cervical Cancer Study Group. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med. 2003 Feb 6;348(6):518-27.
  4. Muñoz N, Bosch FX, Castellsague X, Diaz M, de Sanjose S, Hammouda D, Shah KV, Meijer CJ. Against which human papillomavirus types shall we vaccinate and screen? The international perspective. Int J Cancer. 2004 Aug 20;111(2):278-85.
  5. Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Muñoz N. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999 Sep;189(1):12-9.
  6. Franco EL. Cancer causes revisited: human papillomavirus and cervical neoplasia. J Natl Cancer Inst. 1995 Jun 7;87(11):779-80.
  7. IARC Working Group. Human papillomaviruses. IARC Monographs on the evaluation of carcinogenic risks to humans. Vol. 64, International Agency for Research on Cancer, Lyon, 1995.
  8. IARC Working Group. Human papillomaviruses. IARC Monographs on the evaluation of carcinogenic risks to humans. Vol. 64, International Agency for Research on Cancer, Lyon, 1995.
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