Preventing cervical cancer: vaccinating or freezing?

November 9, 2015 Article BioVox

The group of human papillomaviruses has over 100 types, of which at least thirteen can cause cancer. The virus is present in people all over the world and is mainly spread through sexual contact. Two types of HPV (type 16 and 18) are responsible for two-thirds of cervical cancers and precancerous lesions. Cervical cancer is in the top 5 of most frequent cancers in women and accounts for 7.5% of women’s death due to cancer. In 2012, around 530 000 women developed the disease.

About a decade ago, a vaccine was developed against HPV 16 and 18, however it only protects 50 to 60% of the women who receive the vaccine, as other types of HPV may also cause cervical cancer and girls need to be vaccinated before they become sexually active. Scientists Michael Herfs, Christopher Crum and their colleagues from GiGa (ULG) discovered that this cancer originates from a certain type of cells in the cervix (1) and postulated that destroying these cells could prevent cervical cancer (2).

From esophageal cancer to cervical cancer

Two collaborators of Christopher Crum in Singapore discovered that a very specific type of cells is located where the esophagus and stomach meet, called “junction cells”, and that from these cells a certain type of esophageal cancer may arise. (3). Crum hypothesized that these findings could be extrapolated to cervical cancer as 90% of cervical cancers develop on the junction between the ecto- and endocervix. After thorough investigation of cervical tissue samples, they found that junction cells are also present there. Interestingly, transcriptomic analysis of the junction cells and the neighboring cells revealed a very different expression pattern. Even more striking is that the gene expression pattern in the junction cells is similar to the one that is seen in cervical cancer cells.

Spontaneous regression of precancerous lesions happens within 6 to 12 months in 80% of the cases. In addition, only 20% of the initial lesions have a junction cell expression pattern. These findings led to the discovery that HPV only develops into cancer when it infects junction cells. If other cells are infected, a lesion will form but it will spontaneously regress.

Would cryotherapy be the simple solution?

In the 1950-70s, cauterization of a small area of the cervix after childbirth was common practice. The doctors noticed that this protected against cervical cancer. Michael Herfs is hopeful: “The next step is a clinical trial to validate cryotherapy as a solution to prevent cervical cancer.” Cryotherapy could represent an affordable prophylactic for developing countries where less money is available for vaccinations and screening programs. “We are applying for funding and are discussing with the WHO which countries would be most suited to perform the study. We are looking for a developing country where the prevalence of HPV is high, but where there are also enough doctors and gynecologists available to perform the trial. This is the key issue that we need to resolve.”

In a publication in Nature Reviews Clinical Oncology (2), Herfs and Crum suggest cryotherapy as a standard preventive action, as it is a cheap and risk-free measure.  Herfs: “We don’t think that cryotherapy should replace vaccination, but in many developing countries, women only see a doctor when they are pregnant.”

If we can reduce the risk of women getting cervical cancer by 2 or 3 times through the use of cryotherapy, this is a substantial improvement.

 

References

(1) Herfs, Michael, et al. “A discrete population of squamocolumnar junction cells implicated in the pathogenesis of cervical cancer.” Proceedings of the National Academy of Sciences 109.26 (2012): 10516-10521.

(2) Herfs, Michael, and Christopher P. Crum. “Cervical cancer: Squamocolumnar junction ablation – tying up loose ends?” Nature Reviews Clinical Oncology 12.7 (2015): 378-380.

(3) Wang, Xia, et al. “Residual embryonic cells as precursors of a Barrett’s-like metaplasia.” Cell 145.7 (2011): 1023-1035.


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