Currently, for lack of anything better, this prognostic is established according to three relatively imprecise criteria: a histological criterion (grade 1, 2 or 3, which is a relatively subjective grading given by the examiner), a viral criterion (the identification of the type of HPV to see if it is one of the cancerous strains or not) and a marker called p16 which allows the pathologist to determine whether the virus is present or not, but which has no prognostic value.  In fact, p16 is also positive in HPV infections of the vagina, the vulva, the rectum and the penis.

A few more details to specify…

But that’s not all. Because to be able to assert without any possible contradiction that the junction cells are the only cells capable of causing cervical cancer, it was also necessary to prove that HPV is not responsible for triggering the expression of specific markers in the infected cells, but that these cells already express them to begin with. In other words, that other cells (for instance in the transformation zone, TZ) don’t start to express the same genes once infected by HPV. To do this, Michaël Herfs and his colleagues used foreskin epidermoid cells (circumcision provides a plentiful source) which they put in a culture medium, and infected with two HPV viral oncoproteins, i.e. proteins E6 and E7. Result: neither the normal foreskin cells nor those infected by the viral proteins were able to express the markers characteristic of junction cells. This is indeed proof that the expression of markers is due to the origin of the cell and not infection by HPV. Furthermore, on foetal cells from the cervix, the specific markers of the junction cells are already expressed at 16 weeks of gestation, suggesting an embryonic origin of these junction cells.

And finally, in the last stage for the approval of this publication, it was necessary to prove that once the junction cells had been removed, just like the gynaecologists of 1920 had done, they didn’t return, hence dismissing any risk of the cervix becoming cancerous, even in the presence of HPV. “We were lucky to have access to hysterectomies carried out on patients who had undergone conization following a grade 2 or 3 dysplasia, and then a hysterectomy for another reason. These cases are very rare; I don’t know whether I would have had access to such pieces in Belgium. And we realised that when these junction cells had been excised by conization, they didn’t regenerate. Which brings us back to the hypothesis of 1920, which already postulated that after removal of the junction cells, the patients could still become infected by HPV but that this infection would never degenerate into cancer.”

To such a point that some are already talking about using it as a method to prevent cancer in countries where screening at the gynaecologist’s is a relatively inaccessible luxury – countries that are known to have a high rate of cervical cancer. “But it’s still too early because we still don’t know anything about the possible physiological role of these cells”, Michaël Herfs points out. “Of course they are involved in cancer, but perhaps they are, first and foremost, original cells involved in the renewal of the cervical epithelium, for instance. Getting rid of them, especially in very young women, could have consequences.”