What is cervical cancer?
Cervical cancer or carcinoma of the cervix is one of the few cancers that in almost all cases is caused by a virus, namely HPV (human papillomavirus). There are more than 100 types of the virus. The types of HPV 16 and HPV 18 cause 70% of cervical cancer cases.
Viruses are normally made harmless by the body. However, HPV is particularly well adapted to its host, humans, making it less quickly noticed by the immune system. When it is not detected, there is (at some HPV types), the probability that the DNA is incorporated into the cell of the human being. This two genes are particularly affected: p53 gene and the pRb gene. These two genes, tumor suppressor genes, normally suppress cell division.
The condition develops in the so-called "transition zone" between the columnar epithelium that lines the inside of the cervix duct and the squamous epithelium that the outside of the cervix and the vaginal wall is covered. For there is a true malignancy, there is a stage for years of premalignant changes that can be detected and treated relatively easily.
Risk factors for cervical cancer
- Smoking; is the main factor for the development of cancer in the genital area. Women who smoke have a 1.5 times higher risk of developing cervical cancer.
- DES (DES daughters); DES daughters run a 2-fold increased risk of getting the disease.
- HIV; in the western world have HIV-positive women a greater chance of getting cervical cancer. This is particularly true for women who inject drugs.
- Birth control pills; the chance of developing cervical cancer, is a fraction greater: If one of the pill used in the age of about 20 to 30 years, then increases the prevention of the disease by the time that one is 50, from 3.8 to 4.5 per 1000 people.
- Multiple pregnancies; 5 or more full-term pregnancies as compared to double the risk of one or two full-term pregnancies.
- Number of sexual partners; if there are 6 or more than triples the risk compared to women who have (had) one sexual partner.
- Age at first sexual intercourse; which is less than 18 years, the risk is 2.2 times higher compared to over 21.
- diet / food; particularly green vegetables (cabbage, cauliflower, broccoli, etc.) would reduce the risk.
- Chlamydia probably increases the risk of cervical cancer.
Condom use protects hardly against HPV infection. The risk of cervical cancer is lower in women whose husband is circumcised.
Prophylactic vaccination
Prophylactic HPV vaccination is aimed at the prevention of an HPV infection, and thus the prevention of disease, in particular, the precursors of cervical cancer. The HPV vaccine targets two oncogenic HPV types, type 16 and 18, which are responsible for most cases of cervical cancer. Currently, two vaccines (Gardasil and Cervarix) available, which aim to prevent cervical cancer. HPV vaccination uses VLPs (virus-like particles), which are based on the L1 capsid protein of the above HPV types. As this VLPs consists only of a capsid protein, they do not contain the viral DNA genome, and they are not infectious. With regard to morphology and antigenicity, these particles appear to be very similar to the normal virus particles. These properties make VLPs suitable for use in a vaccine. As the capsid protein per HPV type is different, the VLP's are (and so can also the vaccines), type-specific. Research shows that HPV vaccination premalignant cervical abnormalities may occur.
The antibody titres that are achieved by prophylactic vaccination, be 20 to 100 times above the level of natural infection. After a follow-up of more than five years, is still a very good immune response detectable. There seems to be developing a plateau phase. If this plateau indeed the long-term presence, this could mean that a booster injection to activation of the immune system will be redundant.
Pro and con vaccination
The vaccination of girls or young women before they become sexually active it seems most effective. By this age group to be vaccinated is oncogenic HPV infection at the source will be addressed, and the emergence of abnormal cells and perhaps thereby the incidence of cervical cancer caused by these types could decline. The effect of this will not be visible over decades and is currently not yet proven. To prevent one case of cervical cancer should (in Netherlands) about 200 girls be vaccinated, even assuming the vaccination provides lifelong protection (5 cases per thousand female inhabitants would be prevented, about 7 per thousand walk the disease throughout life on). The number of vaccinations needed to prevent 1 death is about 800. The cost (about 375 euro (2009)) must be in Netherlands additionally by the patient (over 16 years old) itself be paid. A vaccination does not mean that the population screening cervical cancer then is no longer needed; one can still get it. There is no certainty yet about the frequency of side effects. Opponents point out that this is a disease that often (cervical cancer makes 0.3% of the mortality of women from) and which for years the incidence is falling. On 1 april 2008 the Health Council has recommended to the vaccination in the national vaccination programme to record. The first group of girls (born in 1993 up to 1996) is called before the vaccination; as of september 2009 would girls of 12 years are invited to get vaccinated. This has been postponed due to the flu pandemic. However, there are hardly any studies that have been conducted at this age group (12-year-old girls). Currently, there is plenty of research into the so-called catch-up vaccination which is studied or HPV vaccination is also active in women who have been in contact in the past with the human papillomavirus.
In women who have no existing HPV infection (and therefore HPV-DNA-negative (cervix) are), but it is HPV infection have gone through (and therefore HIV positive (blood) are), it appears that the women can be infected with the same HPV type as where they have built up antibodies against. The level of natural protection is not sufficient to prevent herinfecties. Vaccination of these women is shown to work as a booster and to give a faster and better immune response. By this group of women to be vaccinated would be the impact of vaccination on the genesis of lesions may be visible before.
Only in the Group of women that are both HIV-positive and HPV-DNA positive (existing HPV infection) for HPV types 16 and 18 seems to have vaccination no added value. Vaccination works so not only prophylactic and therapeutic.
Outdoor play Netherlands also discussions about the usefulness of this vaccination. In Netherlands is by the producers a comprehensive advertising campaign lined with articles in popular magazines with help of Dutch celebrities. Has never been a new vaccine introduced in the national vaccination programme as soon as the HPV vaccine.
Combination with screening
If the vaccine is 100 per cent effective against HPV16 and HPV18, may occur approximately 70 percent of the cases of cervical cancer. The protective value of the vaccine for low grade abnormalities is about 14 to 25 percent.
By a possible effect of cross-protection would this protection possible in practice may prove wider. Studies are ongoing to identify the possible contribution of cross-protection. On the other hand there is the possibility of replacement type in which viruses other than HPV16, and HPV18 is going to cause a greater number of infections.
Although the availability of an HPV vaccine is an important step in the fight against cervical cancer, there is still a number of comments. HPV vaccination does not offer 100% guarantee that cervical cancer is prevented. Moreover, it is not yet known how long vaccination provides protection.
Vaccination therefore means that the current population screening cervical cancer (the Pap smear) may disappear. We must assume that now HPV vaccination in the national vaccination programme is included, the screening of non-vaccinated girls and women, but also of the vaccinated women even decades (possibly in a modified design) will have to continue. This offers the ability to the effects of vaccination in real life to follow. Opponents point out that this vaccine according to them too fast in Netherlands is entered. In Finland is first additional research done for a decision is taken on the inclusion in the vaccination program.
Therapeutic vaccination
High risk human papilloma viruses infect in the transition area of the ecto-and endo-cervix where the protective epithelial layer is very thin. This allows the virus to infect the basal cell layer to come. If this will be sharing cells and differentiating the virus will proliferate.
After infection are the early proteins E1, E2, E6 and E7 in the basal cell produced. The last 2 proteins have a transformative effect. Therapeutic vaccines are directed against these early proteins. The universities in Leiden and Groningen work both to a private therapeutic vaccine. So far, these vaccines against HPV16.
Only later in the replication cycle of the virus are L1 and L2, the hairstyle proteins of the virus produced to allow the formation of new virions. This is the reason that the late proteins called L1 and L2. As a new infection can only be prevented by antibodies to the mantle of the virus to call up, L1 is taken as a starting point for the development of prophylactic vaccines.