Dr. Rolando Herrero
From the Special Topic of
According to our Special Topics analysis of HPV
research over the past decade, the work of Dr. Rolando
Herrero ranks at #6 by both total cites and by number of
papers, with 59 papers cited a total of 3,191 times. Four
of these papers are included in the top 20 papers lists in
this Topic. In
Essential Science IndicatorsSM
Reuters, Dr. Herrero's work includes 188 papers, the
majority of which are classified in the field of
Clinical Medicine, cited a total of 5,346 times between
January 1, 1998 and June 30, 2008.
Dr. Herrero is a researcher at the
Fundación INCIENSA in San Jose, Costa Rica. In the
interview below, ScienceWatch.com correspondent Gary
Taubes talks with him about his highly cited HPV
What factors or circumstances led you to
your research on HPV and cervical cancer?
Well, when I started my career 25 years ago, we had—and we still
have—an enormous problem with cervical cancer in Costa Rica. It was
clear to me back then that treating cancer that had already developed was
not sufficient—we needed to develop new forms of prevention. I am a
medical oncologist, and as I was finishing my training in the mid-1980s,
there was a large case-control study of cervical cancer starting up, in
collaboration with the US National Cancer Institute (NCI), which included
markers for HPV, and one of the sites was in Costa Rica. I was fascinated
by the techniques, by the epidemiology and particularly epidemiology done
with resources—high-tech epidemiology. I had never seen that before,
because it basically didn’t exist here in Costa Rica. And this
research spoke directly to the origins of disease. It was very, very
exciting, and I started collaborating. I liked it so much that I kept it
"If the vaccine can reach a price
that’s affordable, it can definitely
play a significant role, particularly in
areas where screening programs are very hard
Eventually I became the principal investigator for Costa Rica in that
study. The coordinators—Louise Brinton and William
Reeves—suggested I come to the US and do some analysis of the data at
the NCI. I stayed for three years and planned the next series of studies
while I was there. When I came back, I conducted those studies.
Was your highly cited 2003 New England Journal
of Medicine paper (Muñoz N, et al.,
"Epidemiologic classification of human papillomavirus types associated
with cervical cancer," NEJM 348: 518-27, 6 February 2003)
an NCI collaboration?
No, not at all. In 1995, I moved to France to work at the World Health
Organization’s International Agency for Research on Cancer, IARC, and
there we coordinated a large program, a series of case-control studies,
pretty much along the lines of what I had already done in Costa Rica. But
this was a multi-national, multi-center study. We did multiple studies of
cervical cancer, and a large multi-center case-control study of oral cancer
and HPV. We also did some population-based surveys to assess the prevalence
of HPVs in different areas. I had the opportunity to coordinate, organize,
conduct, and analyze these studies.
Eventually we merged a whole series of the cervical cancer studies into a
pooled analysis of HPV prevalence in these tumors. That was the New
England Journal of Medicine paper with Nubia Muñoz as the first
author. We were looking at all the different types of HPV detected in
cervical cancers. There are about 40 HPV types, and we were able to rank
them based on what fraction of cancers worldwide could be attributed to
each type: HPV-16 is responsible for 50% of cervical cancer, HPV-18 for
What are the challenges to doing this kind of
epidemiological research in Costa Rica that you might not have
Well, there are many challenges to this work in general, particularly when
the studies include new screening methods for vaccines. We have to
coordinate many different groups, because we have the field effort on one
hand; we have the collaborators in the States, the companies, the FDA, all
the independent regulatory boards, and all the committees that supervise
this work on the other. We have laboratories in different areas of the
world that are doing different kinds of assays, all related to the same
projects. This type of coordination is the most challenging.
Then, in Costa Rica, these studies are conducted mainly in rural areas and
that creates logistical and transportation problems. Sometimes it’s
challenging in terms of administration of resources, supervision of
studies. You have to make sure there is appropriate medical supervision.
You have to find the right groups to supervise, make sure you comply with
all the international regulations, which can be stricter than they are
internally. You have to be very active in public relations. You have to
explain to the public what it is you’re doing. And you have to get
the support of your own government, and when you’re collaborating
with other governments, you have to make sure there’s fluid
interaction between them. So all of that can be challenging.
But I would say we also have an enormous advantage here. We have a
universal healthcare system. People are used to being part of it; they
trust the health system and they show a lot of interest in participating in
these kinds of studies.
What professional accomplishments give you the
What I’m most proud of is that we now have developed a very large
team here; we have team of more than 100 people that is fully dedicated to
research on cervical cancer. We have trained scientists, epidemiologists,
physicians, microbiologists, molecular biologists, and statisticians. The
Guanacaste Project is a large research center, fully dedicated to HPV and
cervical cancer. It is a tremendous tool. We are constantly developing new
protocols, new projects, and implementing them in the field. We have
clinics, laboratories, and repositories with computer systems, and
different kinds of populations to study. That is all very rewarding, that
we’ve managed to set up such a large and efficient group. And they
are dedicated. I think it’s unique in terms of how specialized they
are, how focused they are on one condition, which is such a big problem in
Latin America and in developing countries throughout the world.
What is the current focus of your
We’re now doing a large clinical trial of an HPV vaccine against type
16 and 18—the GlaxoSmithKline vaccine. This is being done with
funding from the NCI and the support of several institutions here. It is an
independent trial, by which I mean it’s not sponsored by the company
or run by the company. It is run by the investigators and that gives it a
unique quality. Most drug trials are done and administered, analyzed and
published by the companies themselves. In this case, GSK gave us the
vaccine, but we’re doing the work; we’re doing the analysis and
writing up the publications together with our colleagues at the NCI.
It’s good for everybody and for the company, which would like to see
their results confirmed by independent investigators.
We’re focusing on the efficacy of the vaccine, but we’re also
looking at the mechanism of protection of the vaccine, in relation to the
immune response, humoral, and cell-mediated. We’re very involved in
looking at all these immunological mechanisms, including the genetics of
the immunologic response: what cell groups are activated in response to the
vaccine, and also in response to natural infection.
"...there are many challenges to
this work in general..."
We’re also interested in the impact of the vaccine on the population:
what happens in certain subgroups when they’re vaccinated, such as
different age groups. What happens when you vaccinate women who were
previously exposed to the virus? We had a paper that we published in
JAMA last year, in which we analyzed the efficacy of the vaccine
to induce regression of infections that were already present (Hildesheim A,
et al., "Effect of human papillomavirus 16/18 L1 viruslike
particle vaccine among young women with preexisting infection - A
randomized trial," JAMA 298: 743-53, 15 August 2007).
What did you find?
We found no impact at all on the regression of lesions. There is no
therapeutic efficacy, only prophylactic.
How do you see HPV vaccines playing a role in
The problem is that the vaccine is extremely expensive. It’s
currently out of reach of developing countries, which is where it’s
mostly needed. Eighty percent of cervical cancer cases occur in developing
countries. If the vaccine can reach a price that’s affordable, it can
definitely play a significant role, particularly in areas where screening
programs are very hard to establish. In those areas, if the vaccine is
affordable, it can have significant impact. In a way, it’s much
simpler to give a vaccine than it is to set up a lifetime program that
requires multiple contacts over the course of your life.
What would you like to convey to the general
public about your work?
Well, from a public health perspective, that it’s important to
realize that cervical cancer is a very serious problem. We now have several
very novel ways to prevent it, to control it, and this information has to
be disseminated. We have to make sure that governments do all that they can
to put these programs in place and achieve protection against this disease.
It’s still completely out of control in most developing countries,
while it's almost controlled in developing countries. It’s one of the
most severe examples of inequality, both between countries as well as
within countries. It’s also the poorest women in developed countries
that get this disease, mainly because of a lack of access to the right
health services. I’d also say that it’s very useful to do this
kind of research and very rewarding to collaborate, in terms of the
technology transfer between Costa Rica and the NCI. Not only is there
direct benefit to the public health in Costa Rica, but this problem is
common worldwide and what we learn here can be applied directly to other
countries and contribute to medical knowledge
Rolando Herrero, M.D.
San Jose, Costa Rica
Keywords: HPV, papilloma virus types, vaccine, cervical cancer,
vaccine cost, population-based screening, epidemiology, case-control
studies, Costa Rica.