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Incidence of cervical cancer
- Cervical cancer is the 4th most common cancer in women
- Cervical cancer is the 11th most common cancer overall
- 528,000 new cases of cervical cancer are diagnosed each year
- Responsible for 266,000 deaths annually
The role of Human Papilloma Virus (HPV) in Cervical Cancer
- HPV is a DNA virus from the Papoviridae family of viruses, which infect the basal layer cells of the epithelium
- There are more than 100 different types of HPV, many of which are oncogenic and implicated in a range of cancers including oral, laryngeal and cervical cancer.
- Up to 30 different types can infect the genital region via sexual activity and HPV is believed to be the most common sexually transmitted virus.
Sexually Transmitted HPVs fall into 2 categories:
a) Low risk HPVs: (lr-HPV) do not cause cancer but are responsible for genital warts, e.g. types 6, 11
b) High risk HPVs: (hr HPV) oncogenic (cause cancer).
Prevalence of HPV types varies geographically but hr- HPVs have been found in 99% of cervical cancer.The most common high risk for cervical cancer are types 16 and 18 with types 31 and 33 slightly less prevalent.
The Diagnostic Pathway
Cervical cancer can be treated if the disease is diagnosed early, particularly at the pre-cancerous or CIN stage. The introduction of screening programmes has significantly reduced the incidence of cervical cancer, however the disease still claims 300,000 lives annually worldwide.
Cervical cancer diagnosis worldwide is a multi-step process based on expert assessment of cervical smears (screening) and then the cervix itself (referral) and involves a significant measure of subjectivity. Initial screening (known as a smear test or Pap test or LBC) involves taking a sample of cells from the cervix at the point of care. This sample is then transported to a cytology laboratory where it is examined by a skilled operator.
HPV molecular tests are laboratory-based assays that can identify the high-risk (hr) strains of the virus. These tests are very sensitive, and therefore a negative test would confirm that hr-HPV is absent and therefore the woman is at very low risk of developing cervical cancer. However the tests are not very specific, and with most HPV infections self-resolving, the challenge is how the hr-HPV positive women should be managed. In 2007 the NCI in the USA reported that around 15% of all women were infected with hr-HPV but only a minority of these will go on to develop HG-CIN or cancer.
Those patients with a positive smear result are then referred to a colposcopy clinic for a magnified visual examination/impression of the cervix by a colposcopist who seeks to discriminate between normal, pre-cancerous, and cancerous cells. The colposcopist’s presumed diagnosis of a pre-cancerous or cancerous lesion is in many cases then tested by a diagnostic biopsy. A biopsy is, today, the only way to confirm a presumed diagnosis of a pre-cancerous or cancerous lesion. Ethical and economic issues mean that it is not practical for every woman to have a diagnostic biopsy as a routine screen.
In 2010, about 3.6 million women between the ages of 25 and 60 were screened in England. 330,000 women had appointments in colposcopy clinics in the same year. In the USA 55 million smear tests are taken annually and of these 3.5 million women are referred for abnormal Pap tests or LBC results. Recent changes to the guidelines in the USA mean that women will have screening tests every three years.
Cone biopsy, hysterectomy, LEEP (Loop Electrical Excision Procedure) and LLETZ (Large Loop Excision of the Transformation Zone) remove the whole area of the transformation zone – the area containing all the cells that could become precancerous or develop into cervical cancer.
A virus called human papilloma virus, or HPV is the major cause of cervical cancer. Vaccines to prevent this infection have now been developed and two have been licensed for use within the EU and other developed countries including the USA; one is Gardasil from Merck & Co and the other is Cervarix from GlaxoSmithKline. These vaccines protect against strains of HPV most likely to cause cervical cancer, but are not completely protective against all strains and the screening process will remain an important element of cervical cancer prevention.
Both vaccines target HPV types 16 and 18 which cause about 70% of cervical cancers. Gardasil also includes HPV types 6 & 11 responsible for around 90% of cervical warts.
Facts about the vaccines
The vaccines are highly effective in preventing infection by these specific types of HPV in young women who have not been previously exposed to them. Neither vaccine will treat existing HPV infections or their complications.
The length of protection (immunity) is usually not known when a vaccine is first introduced. So far, studies have found that vaccinated persons are protected for six years. More research is being done to find out how long protection will last and if a booster dose will be needed. In the medium term, screening will still be required to assess the effectiveness of the vaccines.
The vaccine is most effective for girls/women who get vaccinated before their first sexual contact. For this reason national guidelines suggest that it is important for girls to get vaccinated before they become sexually active. In the UK and USA, the guidelines recommend vaccines for all girls between the ages of 11 and 13. Most girls and women above this age group will have not received the vaccination and as a result will still require screening.
Ongoing need for screening
Whilst the vaccines may reduce the incidence of cervical cancer over time, it will still be necessary to screen women. The reasons for this are:
- The vaccine will NOT provide protection against all the types of HPV that cause cervical cancer, so women will still be at risk for some cancers.
- Women over the age of 13 will not be vaccinated and therefore require screening until they are 65 years old
- 20% of women will not be vaccinated
- Vaccine immunity studies cover only 6 years
- Some women may not get all the required doses of the vaccine (or they may not get them at the right times) so they may not be fully immune.
- Women may also not get the vaccine’s full benefits if they had already acquired HPV type 16 or 18 before vaccination.
It is important to realise that whilst current screening methods have helped reduce the incidence of cervical cancer, these methods will not be fit for purpose in an environment with lower incidence through vaccination.