To date, scientists have identified around twenty human papillomaviruses (HPVs) that cause cervical cancer – the first type of cancer to be recognized by WHO as being exclusively attributable to a viral infection. But the most common types are HPV 16 (responsible for 55% of cases) and HPV 18 (responsible for 12% of cases). These cancerous HPVs can also affect other mucous membranes and lead to anal or oropharyngeal cancer.
Human papillomaviruses or HPVs infect the epithelial cells in the skin or mucous membranes and are transmitted when these cells spread through a process known as desquamation. While some HPVs are low risk, causing benign lesions, other high-risk HPVs may lead to cancer. The HPVs that affect genital mucosa are sexually transmitted and occur frequently, from the very beginning of active sexual life – they are found in a third of women between adolescence and their early twenties. Although infections caused by HPVs can occur throughout adulthood in sexually active women, they often give rise to no symptoms and clear up by themselves. But in 3 to 10% of infected women the infection is persistent, and some of these will go on to develop precancerous lesions known as cervical intraepithelial neoplasia, a precursor to cervical cancer. Several years may go by between initial infection with a cancerous HPV and the emergence of cancer.
A few figures
At global level, cervical cancer is responsible for approximately 250,000 to 300,000 deaths and 500,000 new cases each year (80% in developing countries), according to the International Agency for Research on Cancer. In Europe, nearly 65,000 women are affected, and approximately 25,000 new cases are reported annually, with a death rate of 4.7%. In France, there are 3,000 cases and more than 1,000 deaths each year, and around 30,000 women receive a diagnosis of high-grade cervical neoplasia or cancer each year.
Precancerous lesions are generally treated by surgery ("conization"). Cervical cancer is treated by a combination of surgery and radiotherapy with adjuvant chemotherapy, which is effective in early stages. Therapeutic vaccines for the treatment of precancerous lesions and cervical cancer caused by HPV 16 and/or HPV 18 are currently in clinical trials.
Cervical cancer prevention currently involves methods to prevent sexually transmitted infections (condoms, screening for sexual partners) and especially routine cervical screening in women. A prophylactic vaccine that protects against infection with HPV 16 and 18 – thereby preventing two thirds of cervical cancers – is currently available. This vaccine has no therapeutic benefits and does not protect women who have already been infected. The opinion delivered on September 28, 2012 by the French High Council for Public Health (HCSP) states that vaccination is recommended for girls aged between 11 and 14 and that every opportunity should be taken to encourage administration of the vaccine. The HCSP also recommends that catch-up vaccination should be limited to women aged 20 or under, since the vaccine is most effective if administered before exposure to the risk of HPV infection.
At the Institut Pasteur
In collaboration with Institut Pasteur start-up Genticel (previously known as BT Pharma), the teams led by Claude Leclerc (Immune Regulations and Vaccinology Unit, Institut Pasteur/Inserm 1041) and Daniel Ladant (Biochemistry of Macromolecular Interactions Unit, Institut Pasteur/URA 2185 CNRS) established proof of concept for a therapeutic cervical cancer vaccine. Genticel used this discovery to develop a bivalent vaccine candidate aimed at treating women who have already been infected by HPV 16 and/or HPV 18 and are therefore no longer eligible for the preventive vaccines currently on the market. In 2010, Genticel obtained authorization to launch phase 1 clinical trials.
Didier Guillemot, Head of the Pharmacoepidemiology and Infectious Diseases Unit (Institut Pasteur/University of Versailles Saint-Quentin-en-Yvelines/Inserm U 657), is involved in a large-scale national study on student health as coordinator for infectious issues. The initial investigations will aim to determine the prevalence and distribution of HPVs and the dynamics of infection by these viruses among vaccinated and non-vaccinated female students.