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Médico de Canencia de la Sierra, Garganta de los Montes y El Cuadrón (Madrid) España
Equipo CESCA, Madrid, España
English translation by Juan Gérvas (“nogracias” Spain, http://www.nogracias.eu) and Joana Ramos, (www.healthyskepticism.og )
En 2007 se ha comercializado de la vacuna contra el virus del papiloma humano, con la que se propone vacunar a niñas de 11 y 12 años para la prevención primaria del cáncer de cuello de útero, dada la fuerte asociación entre el cáncer y algunos tipos oncogénicos del virus. La vacuna ha sido rápidamente incluida en los calendarios vacunales de la mayoría de los países desarrollados. En este texto se revisa el fundamento científico de dicha decisión. Son puntos clave: la ausencia de cambios en la epidemiología de la infección, la estabilidad o disminución del la incidencia y mortalidad del cáncer de cuello de útero, la falta de correlación entre respuesta inmunitaria serológica y la inmunidad natural, el impacto de la vacuna en la ecología del virus, las evaluaciones coste-efectividad que dependen de la duración desconocida de la inmunización, la dependencia excesiva de la investigación financiada por la industria farmacéutica, y la necesidad de mantener la citología de cribado. Se precisaría más tiempo e información antes de introducir la vacunación en el calendario vacunal.
Palabras clave: Vacunas, Virus del papiloma humano, Evaluación.
Sales of the vaccine against human papilloma virus began in 2007, promoted for administration in girls 11 -12 years old, as preventative measure against cervical cancer, due to the strong link between this cancer with the presence of certain oncogenic strains of the papilloma virus. The vaccine was quickly included in the official immunization programs in many developed countries. In this paper I review the scientific basis for that decision. Critical questions for review are: the absence of changes in the epidemiology of the infection; stability or reduction in the incidence and mortality from cervical cancer; lack of correlation between levels of serologic immune response and natural immunity; the effect of the vaccine on virus ecology; evaluation of the cost-effectiveness of immunization in the face of lack of definitive information about the length of its effectiveness; pharmaceutical industry sponsorship of most of the HPV vaccine research; and the need to maintain screening with Papanicolau exams. More time and information are needed before including this vaccine in the official immunization program.
Key words: Vaccines, Human papilloma virus, Evaluation.
Eleven basic questions (with no definitive answer)
With a speed never before seen in the field of immunization, the HPV vacccine has been added to the vaccination schedules of almost all the European countries, including Germany, Austria, Belgium, Denmark, Spain, Greece, the Netherlands, Italy, Luxemburg, the UK, and Switzerland (1) and in other developed nations like Australia, Canada, and the USA.
Does this mean that there is complete agreement and solid scientific basis for this action? No.
The field of preventive medicine is a whole different matter as we can learn from other cases; for example, with respect to screening of newborns for hip displasia (2-4).
Reasonable doubts exist about the rationale for the decision to include the HPV vaccine in the immunization schedules. At the very least, there are eleven basic unresolved questions, which raise doubts about the appropriateness of its inclusion in the new [vaccination] schedule.
Have there been any recent changes in our understanding of the papilloma virus infection? No.
In fact we do not know its natural history. It is the most common sexually transmitted disease, but most cases are benign (90% clear spontaneously) (5). We still don’t know why some infections become chronic and cause cancer (it takes about 20-30 years for [the infection] to transform into cervical cancer).
In most developed countries mortality is stable or decreasing.
No. In Spain, for example, the incidence has remained stable to low, as has the monthly rate (some 7. 11 cases and 2.4 deaths yearly per 100,000 women, respectively) (6). In the USA, there has been a decrease, and there are about 11,100 new cases and about 3700 deaths from cervical cancer annually (5).
In most cases, the quantity of blood antibodies is very low to nonexistent (in half of all cases) among women with natural immunity. Infection does not correlate with viremia (viral replication occurs on the epithelial surface, very far from the antigen-presenting cells and from the macrophages) (7). Viral replication is a cellular phenomenon. We do not understand very well the normal immune response, but it is very effective. Furthermore, it does not seem to be affected by re-exposure resulting from ongoing sexual activity.
There is no immunological correlation shown at all. The vaccine’s mode of action is unknown. It is theorized that antibodies in blood might help in getting rid of the infection, but we don’t know how (5,8). Natural immunity is cellular, not serological.
For example, the vaccine might reduce chronic infections and pre-malignant lesions caused by the viruses which the vaccine acts against (helpful). But if this eliminated other human papilloma viruses, we wouldn’t know how to assess such a change. For example, co-infection with types 6 and 11 (low cancer risk) naturally decreases the probability of infection by type 16 (high cancer risk) (9). It is generally accepted that the vaccination blocks the appearance or activation of the viruses that it targets. Because of these changes occur in the “ecology” of the uterine cervix and surrounding areas, and there are data (10) to support the existence of an “empty niche” effect, that permits the proliferation of other high cancer risk viruses, or that permits the transformation of low-risk viruses into high-risk ones.
There are no clinical data about its effectiveness, nor have there been clinical trials showing health outcomes for girls in the age group being targeted for vaccination. There is data showing almost 100% effectiveness (results from clinical trials conducted under the most ideal conditions, quite different from real-life clinical practice) for lesions associated with the viruses that the vaccine targets, in women ages 16 to 26, who were mostly white, healthy, well educated and living in developed countries (10-14). When “intention to treat” is taken into account (if all patients who participated in the trials are included, even if not meeting ideal inclusion criteria), the vaccine’s effectiveness decreases to 50% (10-14). And if all those patients whose cervical lesions are not associated with the viruses targeted by the vaccine are included then the rate of effectiveness of the vaccine falls to 17% (11).
So far, it has been shown to work for five years. If immunity would decrease, then re-vaccination would be necessary after a certain length of time. Besides the expense and logistical complications this would entail, we do not know if inducing artificial immunity would inhibit natural immunity, resulting in serious and more aggressive oncogenic infections. (something similar to what has happened with small pox vaccination) (7,12).
But some unproven assumptions have been made about its effectiveness and duration of immunity it offers. In fact, under ordinary conditions, if the period of immunity from the vaccine lasts less than 30 years, and if its rate of effectiveness is 70%, in the case of Canada, then it is not cost-effective at all. In other words, it would be necessary to vaccinate all girls in order to prevent one case of cervical cancer (15).
Women get the infection when they become sexually active. Clinical trials done under ideal conditions show that the vaccine has very low efficacy in sexually active women, about 17% (10,16). The vaccine is prophylactic (blocks transmission), not therapeutic (which would eliminate virus in the epithelial cells) (5, 10).
The bulk of the research on the HPV vaccine has been, is, and will continue to be dependent on the manufacturers of the vaccine. It is unclear why the governments of wealthy countries have declined to take an active role in this area of sexual health services, and instead have assumed merely a passive role as “payor” for the vaccine (10).
Is it still necessary to continue the current early dectection programs for cervical cancer? Yes.
Current screening programs to detect cervical cancer by cytology (Pap smears) have serious problems in terms of patient access as well as scientific basis, the vaccine doesn’t replace them, as the vaccine only acts against 2 of the 15 oncogenic viruses. We do not know how the specificity and sensibility of screening tests should be modified (5,7).
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