The origins of cervical cancer

More than 500 000 women are affected by cervical cancer every year. We know that this cancer is nearly always linked to an infection by a papilloma virus or HPV. Thanks to the work (1) of Michaël Herfs and his colleagues, we now know that it all begins with a few cells very precisely located in the cervix that have never been observed until now. And why this type of cancer can only occur within these cells and not elsewhere.

Schéma-uterusThe doctoral thesis of Michaël Herfs, an FNRS postdoctoral researcher in the University of Liège’s Department of Pathological Anatomy and Cytology, focused on the immunological aspects of cervical cancer. Applying for a postdoc at the prestigious Brigham & Women’s Hospital in Boston, in Christopher Crum’s department of anatomy and pathology was, of course, the logical choice. Because in this hospital entirely dedicated to gynaecological and maternity problems, the doctors have been paying particular attention to this type of cancer for a very long time. In 1920, they had already (!) noticed that by cauterising a certain area of the cervix, which they usually did just after a birth, they were able to protect the young mothers against the risk of this type of cancer for the rest of lives. This particularity couldn’t be explained at the time but since then, the cervix has been a particular area of interest for the various heads of this department over the years. Christopher Crum is no exception to the rule; in fact, he already had a notion about the issue. And as chance would have it, this young postdoctoral Belgian was to inherit this hundred-year-old mystery…

A cancer due to a virus  

But first of all, let us set the scene. According to the WHO’s figures, cervical cancer is the second most common cancer in women. It currently affects 530 000 every year worldwide, and 275 000 die of it, mainly in developing countries. In industrialised countries, these deaths are far more rare, thanks to simple and highly efficient screening: the cervical smear test. Ideally carried out every three years in all women, from the beginning of sexual activity until 65 years of age, it allows precancerous lesions (dysplasias) to be detected by microscopic examination of cell samples taken from the cervix using a spatula. The dysplasias can be eliminated by a simple intervention known as conization (a conical piece of the cervix is removed).

We have also more recently discovered that cervical cancer is almost always linked to an infection by the papilloma virus, or HPV (Human Papillomavirus). This family of HPV is very common, but only a number of types are responsible for cancer. A vaccination against “cervical cancer” has been available for several years now, though to be more precise, the vaccine protects against the main strains of carcinogenic HPV, i.e. 16 and 18.

Making the most of intuition

When Michaël Herfs first contacted Christopher Crum six months before going to the States, it was agreed that he would work on grade 1 dysplasias; we know that 85 to 90% of them spontaneously regress, though this phenomenon remains unexplained (see Classification of cervical cancer). In fact, this is why these dysplasias are rarely treated when they are discovered through screening; in general, a test is done again after six to twelve months. A biopsy, and possibly conization, is carried out only if the lesion hasn’t disappeared.  But when the anatomic pathologist examines these grade 1 dysplasias under the microscope, it is impossible for him to predict which of them will progress and which will regress.  Michaël Herfs therefore had to attempt to identify the specific markers that would allow him to fine tune this prognosis. But fate had a big surprise in store for him…

(1) A discrete population of squamocolumnar junction cells implicated in the pathogenesis of cervical cancer. Michael Herfs, Yusuke Yamamoto, Anna Laury, Xia Wang, Marisa R. Nuccia, Margaret E. McLaughlin-Drubin, Karl Münger, Sarah Feldman, Frank D. McKeon, Wa Xian and Christopher P. Crum

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