History of Human Papillomavirus in Venezuela

 An Update on the History of Human Papillomavirus in Venezuela       and its causal Relation to Cervical Cancer

 

On October 1971, in Maracaibo Venezuela, at the VIII Congress of the Latin-American Society of Pathology (SLAP), two doctors from Venezuela, Jorge Nágel, a gynecologist, and Elio Casale, a pathologist, both practicing in Caracas, presented the findings of their research in a free paper: by using an electron microscope (EM), they had found pink spots on cervical lesions which revealed the presence of viral particles.

José Trinidad Núñez Montiel was a Venezuelan gynecologist and a renowned colposcopist in Sweden and Argentina, two destinations where he used to lecture. During his conference presentations, he would speak of "mosaics" and "vascular squares", obscure terms for most Venezuelan gynecologists (at the time, the importance of the colposcope as a diagnostic tool was mostly overlooked even by American doctors). This was not the case of JT Núñez Montiel. He was able to show the location of dysplasia in the most hidden parts of the cervix by opening the entire endocervical canal with forceps and spreading it with lugol.  When Nuñez Montiel heard the words spoken by Nagel and Casale at SLAP’s VIII Congress, he immediately realized that, with a colposcope and an electron microscope (EM), we could solve the problem of the origin of cervical cancer. We had already examined samples of the cervix, and studied trichomonas and their effect on the cervical epithelium. We had inspected cases of trichomoniasis with the EM and we decided to publish our findings in several papers that were to be printed in later years^{1, 2, 3. 4}. We knew that the Human Papilloma Virus (HPV) produced warts on the skin as well as condylomas on the mucous membranes, which clearly were real tumors. Those cauliflower-like growths were genital warts, gynecological tumors observed in low-income women; it seemed to us that cancer and poverty went hand in hand.

 

As soon as the 1971 SLAP Congress concluded, we focused our attention on taking biopsies and look for HPV particles in the cervix.  We found the virus in vaginal exudates and biopsies. We detected HPV particles in the nucleus of numerous cells. We highlighted ultrastructural features that were still unknown at the time -since the histological samples only showed changes which back then were misinterpreted as glucogenic overload. We would later understand –through a simple staining procedure with Schiff's reagent- that glycogen did not cause the changes in the ectocervical epithelium. It proved difficult to convince my fellow pathologists that those coilocytic halos in the histological sections were not glycogen. When Nuñez Montiel told them about the viruses, they simply laughed, because at the time, nobody believed us.

 

In September 1973, at the following Latin American Congress of Pathology (IX) held two years later in Merida, in the Mexican peninsula of Yucatan, I presented our findings in two free papers. After my presentation, Dr. Javier Arias Stella, who had been sitting in the audience, approached me and said that he didn’t think I was aware of the importance of what I had just revealed but that I should know that it was something crucial. It is strange how life works itself out. Many years later, in the early nineties, we were to experience those days again in San Sebastian, in the Basque Country.  On a cold rainy November day, facing the Cantabrian Sea and surrounded by Saudi and many good friends, we had the privilege to listen to a beautiful lecture on our specialty delivered by Javier Arias Stella where he spoke with great reverence about my 1973 adventure.  His lecture was printed in a 1993 issue of the Journal of Pathology of the Latin American Society of Pathology (SLAP), in Mexico⁵ , and refers to the presentation of the two free papers of the IX SLAP Congress in Merida (Yucatan, Mexico, September 1973) which were published in the Congress proceedings (Pathology magazine supplement (Mex), and which, not surprisingly, had a poor circulation^{6, 7} .

 

The official beginnings of the history of HPV and the inception of publications on the virus and its link to cancer would in fact kick off with the cytological changes described by Meisels and Fortin⁸ and Puroloa and Savia⁹ in 1976, and stated by ZurHausen a few years later¹⁰. A printed summary of our findings was later published in 1978 in a Venezuelan medical journal considered a thriving periodical publication at the time¹¹. Aside from summarizing our extensive experience working in Maracaibo, the goal of the paper was also to pay tribute to the incredible personality of JT Nuñez Montiel.  It therefore began with the following epigraph: "This research on cervical-vaginal papillomatosis is the product of the concerns and tenacity of José Trinidad Núñez Montiel, a brilliant gynecologist from the state of Zulia, who unfortunately is now deceased. He was very sad and disappointed to see how his colleagues, both from inside or outside the University of Zulia, underappreciated his efforts on cervical cancer research. This work is the product of his ideas. It is my hope that it will serve as a posthumous tribute to his memory. "

 

A few years later, I met Francisco (Pancho) Rincón Morales, a self-described proud disciple of JT Nuñez Montiel’s work and ideas. The two of us resumed our work, focusing on the subject of our shared interest: vulvar lesions caused by HPV. In the following years we were to collaborate at the UCV (Central University of Venezuela), performing transmission and scanning electron microscopy studies. Our observations lead to several publications^{12, 13, 14}. While cervical carcinoma was still leading cancer mortality rates in our country, we were simultaneously confronted with problems related to the practice of illegal medicine as a significant number of cytotechnologists were not working under the supervision of a pathologist. This irregular situation led to multiple discussions and controversies between the MSAS (Venezuelan Health Department) and cytotechnologists. Our legal position, shared by the Venezuelan Pathologist’s Association, was backed up many times by the Venezuelan Medical Federation. But instead of improving cytological early diagnosis, it produced the adverse effect. The situation worsened and the disagreements only increased, particularly after I shared my thoughts with the press in Caracas and Maracaibo and published the truth in a book entitled "Reflections of a Pathologist"¹⁵, a publication sponsored by the Venezuelan Society of Pathological Anatomy in 1991.

 

The sequel, "More Reflections on Pathology and the Country", published in 1998¹⁶, included press articles from El Nacional, Panorama, El Diario de Caracas, etc. on the subject of cancer and cytological diagnosis. Each article repeatedly focused on the story behind what Pancho used to call, "the ignominious figure", which exposed the truth behind those cruel statistics; the numbers showed that instead of declining, and despite more than 50 years of screening cytology for cervical cancer, cervical carcinoma in Venezuela was on the rise. We always felt that these numbers spoke of underdevelopment or perhaps even of tropical entropy, this distinctive disorder or unaccountability that so often characterizes our governing leaders, people who should have focused on eradicating cervical cancer from our country.

 

Perhaps because of the "idiosyncrasy" argument or because of the way us Venezuelans see things, always on the surface, without ever delving deep into the subject, we have unfortunately lost precious time. As a matter of fact, we still are. Meanwhile, the health conditions of our patients -who are for the most part poor- is slowly deteriorating. Politicians either fill their pockets or tend to talk a lot and do very little. Therefore, oddly enough, it seems easier to blame all our troubles on "the devil’s black excrement" as Perez Alfonso used to call our petroleum, a natural resource which has made our nation so rich and our people so poor. However when you read our statistics on cervical cancer, which are outdated and unreliable, it is hard to hide the fact that we have no trustworthy National Cancer Registry to speak of.

 

References

1 -Luzardo Batista M, García Tamayo J, Nuñez Montiel JT. Anatomía submicroscópica del exocervix humano normal. InvestClin(Ven) 1969, 30:25-56.

2 -Luzardo Batista M, García Tamayo J, Nuñez Montiel JT. Ultraestructura de la membrana basal y células basaes del exocervixhumano normal. Rev Ven Obstet & Ginecol. 1970,30: 13-25.

3 -García Tamayo J, Nuñez Montiel JT, de García HP. Tricomoniasis vaginal humana. Estudio ultrestructural e histoquímica. Invest Clin (Ven) 1972, 13: 2-14.

4 -García Tamayo J, Nuñez Montiel JT, de García HP. An electrón microscopio investigation of human vaginal trichomoniasis.Acta Cytol (USA) 1978, 22:447-455.

5 -Arias Stella, J. Patología en un país en desarrollo.Experiencia de una vida. Patología (Mex)1993, 31:1-5.

6 -García Tamayo J, Núñez Montiel JT. Identificación de partículas virales en el exudado vaginal de pacientes con papilomas ycondilomas genitales. Resumen publicado en Patología (Mex)Supl 1-11,81, 1973.

7 -Núñez Montiel JT, García Tamayo J. Colposcopia, histopatología y ultraestructura de papilomas y condilomas genitales.Resumen publicado en Patología(Mex) Supl 1-11, 86, 1973.

8 -Meisels A, Fortín R. Condylomatous lesions of the cervix and vagina. Cytologic patterns. Acta Cytol 1976, 20: 505-509.

9 -Puroloa E, Savia E. Cytology of gynecologic condyloma acuminatum. Acta Cytol 1977,21: 26-31.

10 -ZurHausen H. Virus in human cancers. Science 1991, 254:1167-1172.

11 -García Tamayo J, Núñez Montiel JT. Investigación con el microscopio electrónico sobre la papilomatosis cérvico-vaginal.Acta Médica Venezolana (Ven) 25(3-4): 132-138, 1978.

12 -Rincón Morales F, García Tamayo J. Infección por virus papiloma humano de la vulva. Aspectos clínicos, histológicos yultraestructurales. Rev Ven de Obst y Ginecol (Ven) 43: 203-215, 1983.

13 -García Tamayo J. Infección con el virus del papiloma humano y cáncer del cuello uterino. Rev. Fundación José María Vargas.Ven) 30: 177-187, 1984.

14 -Borges de, R, García Tamayo J, Zaittman M. Cytologic and ultrastructural findings of a peculiar alteration of cervical cells inpatients with HPV infection. Acta Cytol (USA) 33: 314-318, 1989.

15 -García Tamayo J. Reflexiones de un Anatomopatólogo. Sociedad Venezolana de Anatomía Patológica. Eds., 1991.  \              16 -García Tamayo J.  Mas reflexiones sobre la patología el país. Sociedad Venezolana de Anatomía Patológica. Eds., 1998.

 Maracaibo, domingo 6 de marzo de 2022