At around the same time, Frank McKeon and Wa Xian, two long-term collaborators of Christopher Crum working in Singapore, published an original article in Cell describing a population of very particular cells located at the junction between the mucosal surfaces of the oesophagus and the stomach. The results of this study confirm that these “junction cells” lie at the origin of a type of oesophageal cancer which develops in an area of mucous membrane transformed by gastric acid (metaplasia) called Barratt’s oesophagus. For Christopher Crum, who has every respect for intuition since he knows that it sometimes contains a seed of genius, here was a challenge for the taking: “and what if it was the same for the cervix?” So here was our young researcher from Liège propelled in an unexpected direction…that was to lead to an expected success!

“The starting point was two already very old observations”, Michaël Herfs summarises. “On the one hand, the fact that 90% of cases of cervical cancer develop close to an area known as the “transformation zone” located between the ectocervix and endocervix, and the observation made by doctors at Harvard in 1920, that when this zone is cauterized, the patients never develop cervical cancer thereafter. We therefore wondered what was the cradle of the cancer in the microenvironment of this transformation zone and what, when it is removed, protects against this cancer, since women are always potentially in contact with the carcinogenic HPV.”

Bingo!

Michaël Herfs therefore focused on the task in hand by starting very logically – like any good researcher in anatomic pathology – and examining the HPV-negative biopsies of the cervix in search of these famous junction cells. A good hundred biopsies. It must be said, he was in the right place for it: the Brigham & Women’s Hospital in Boston is the leading “Women’s Hospital” in the United States. Gynaecological pathologies make up 70 to 80% of the biopsies. “If you want to make a comparison,  at the University Hospital in Liège, we maybe get 40-50 cases of cervical biopsies that are HPV-positive or not per year; here, I was getting three or four a day”, Michaël Herfs stresses.

The task wasn’t simple: first of all, the biopsies had to be done in the right place, and correctly oriented in the longitudinal axis of the cervix to be able to explore the junction between the two coatings. An orientation that depends on luck: only 10% of the biopsies meet these criteria. But what does it matter when we are burning with zeal! By continuously looking down his microscope, Michaël Herfs finally saw what he was looking for: very small, cuboid and pink with a nucleus right in the middle, all curled up and quite different from their epidermoid neighbours (mucosal surface of the ectocervix, similar to the vaginal epithelium) or glandular cylindrical cells (mucosal surface of the endocervix, similar to the epithelium inside the uterus). How come no-one had noticed them before? “It seems impossible! Especially considering that since we spotted them, we have the impression that that’s all we can see! But it can be explained by the fact that there are so few of them: an area of 40 cells in width, at the most. Forty cells in a 1-cm biopsy, that’s a few microns; it’s easy to miss them!”