More than 90% (possibly as high as 99%) of cervical cancer is related to previous infection with human papillomavirus (HPV), also known as the wart viruses. HPV is a double-stranded DNA virus. Viral replication causes changes within cells which can sometimes lead to the cell becoming cancerous. Different types of HPV affect different tissues; some cause warts on hands, some cause warts on feet (verrucas) and some cause anogenital warts (with the slightly over the top medical term, condyloma acuminatum). There are more than 200 different types of HPV, many of which can cause cancer, including oropharyngeal, laryngeal cancer, and sometimes even skin cancers, however perhaps the best known link is to cervical cancer.
HPV types 16 and 18 cause 70% of all cervical cancer with types 31, 33, 45, 52 and 58 bringing this up to 90% of cervical cancer. About 3000 cases of cervical cancer are diagnosed a year in the UK, mainly in sexually active women aged 30-45 years. However of the five million women in the UK invited to cervical screening each year, one in four do not attend. Cervical cancer continues to causes 900 deaths annually despite it being the most preventable form of cancer in women.
How do we detect women at risk of cervical cancer?
The traditional method for screening women for precancerous cells on the cervix was using cytology to look at cells collected from the cervix by Papanicolaou smear (often shortened to the Pap smear or just smear test). Georgios Papanikolaou developed the technique of detecting cervical cancer in 1928 by studying cells from the cervix; however his technique was not accepted into more routine practice until 1943, when the modern science of cytology was “invented”.
The current recommendation in the UK is for women between 25 and 49 years old to have a smear every 3 years, and then every 5 years until 64 years old. That’s 12 smears! Now I suspect there are a lot of women out there who hold no love for Georgios Papanikolaou and many will even go as far as saying the smear could only have been invented by a man! I get this!! I understand it is an unpleasant, embarrassing and often painful procedure to undergo. Screening however has been responsible for detecting many cases of precancerous cells and early cervical cancers which can then be cured by relatively minor surgical excision. Screening has undoubtedly saved many lives over the years with current estimates being that yearly in the UK 5000 deaths from cervical cancer are prevented by detecting abnormal cells before they develop into cancer.
Recently, there has been a change to cervical screening in the light of our knowledge about HPV being the cause. Nowadays most cervical smears are tested for HPV first and only by cytology if HPV is detected. Essentially this two-step approach uses the “over sensitive” HPV test to decide which samples need the more specific but time consuming cytology assessment. The HPV screen is good for saying a sample is negative whereas the cytology examination is good for saying a sample is positive; and together they are more accurate at determining true positive or negative tests.
Women still have to have the same number of smears; at the moment it is only the way the samples are tested that has changed.
If a samples tests positive for one of the high risk types of HPV then cytology will be performed. If the cervical cells look abnormal then the woman will need further examination by colposcopy. Colposcopy is a procedure where the cervix is directly visualised and further investigation or treatment including minor procedures can be undertaken. If there are no abnormal cells then a further smear will be done in 12 months’ time to see if there have been any changes, this is because 40% of women clear the infection naturally in 1 year, and 60% within 2 years, and not go on to develop precancerous cells. Cervical cancer won’t develop during this time; remember it is a screening test for precancerous cells not cancer itself. If HPV is still detected at 2 years then a colposcopy referral will be made.
I would strongly recommend anyone who wants to know more to visit the Jo’s Cervical Cancer Trust website as it has lots of excellent information presented in an easily understandable way.
How is HPV detected?
HPV in cervical smears is usually detected using a PCR based method for viral mRNA from specific high risk types of HPV as well as certain cancer genes. Locally we use a CE marked approved test that detects the presence of HPV by looking for mRNA from the highest risk types of HPV 16/17/45. In addition the test also looks for mRNA from two genes (E6 and E7) that encode proteins that can trigger cervical cells to become cancerous, known as oncogenes (from oncology, the science of cancer). The high risk types of HPV detected by our local test are 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68.
The published figures for the positive predictive value (PPV) of our local test for detecting precancerous cells is only about 7-20% which may seem very poor BUT the negative predictive value (NPV) is high at about 99.6% for more advanced cervical cell changes, which means that the false negative rate is 4 in 1000 patients and this is actually very good i.e. the test is very good at telling you haven’t got precancerous changes.
Screening tests are designed to have the best negative predictive value possible as they would rather over diagnose a condition and carry out further tests than miss the condition.
How might HPV vaccination change the cervical screening program?
Between 2007 and 2009 HPV vaccination started in the UK for girls aged 12-13 and now these girls are approaching the age for cervical screening. The vaccine is called Gardasil and contains proteins from HPV types 6/11/16/18; it does not contain live virus. In clinical trials it prevented 100% of 16 and 18 infections and it is expected to reduce cervical cancer rates by over 70%.
The way in which the HPV vaccine might affect the cervical screening program is firstly by making cervical cancer much less likely and secondly by altering the pre-test probability of a positive screening test. Let me explain further…
If a condition is very common in a population then a positive test that detects the condition is more likely to be a true positive and a negative test is more likely to be a false negative. Conversely if a condition is very uncommon then a positive test is likely to be a false positive whereas a negative test is likely to be a true negative.
In the case of cervical screening as cervical cancer becomes less common the better the screening test becomes at predicting negative results i.e. a negative test becomes more reliable. On the other hand the positive tests become more likely to be false positives. The effect of the screening program becomes better at excluding cervical cancer risk.
What might this mean for the future cervical screening program?
A recent paper by a team from Queen Mary University of London has looked at how HPV vaccine might theoretically influence how many cervical smears a woman might need to prevent cervical cancer from developing. They looked at numerous vaccination scenarios including effectiveness of the vaccine at preventing infection, the amount of the population vaccinated, potential cross protection to other types of HPV and possible effects of waning vaccine protection over time.
The main headline conclusion from the paper was that women who have been vaccinated against HPV only need 3 cervical screens, after a negative HPV test, during their lifetime to prevent a rise in cervical cancer rates. This has been translated by the mass media to be “all women only need three smears in their lifetime” but this is not what the paper actually says. The paper says VACCINATED women would only need three smears AFTER their first negative HPV test; unvaccinated women would still need the same frequency of screening that they currently get.
In addition, the paper comments on recent decisions by the Netherlands and Australia to move to five yearly screening of all women and the mathematical models suggest this will actually result in an increase in cervical cancer rates in unvaccinated women in these countries. That’s very worrying for most women and begs the question “is 5 yearly screening actually about saving money?”
So in the future, HPV vaccine may lead to a three prong approach to screening for cervical cancer. All patients will have a smear at 21 years old and be screened for HPV infection and vaccination status.
It will be fascinating to see how this goes. A vaccine that prevents cancer is always going to be important and a vaccine that also saves a huge amount of unnecessary invasive investigation and anxiety as well as potentially saving a lot of money as well is of even more interest. So NO, you cannot cancel your smear… but our young girls may have less to endure in the future.
How do we detect women at risk of cervical cancer?
The traditional method for screening women for precancerous cells on the cervix was using cytology to look at cells collected from the cervix by Papanicolaou smear (often shortened to the Pap smear or just smear test). Georgios Papanikolaou developed the technique of detecting cervical cancer in 1928 by studying cells from the cervix; however his technique was not accepted into more routine practice until 1943, when the modern science of cytology was “invented”.
The current recommendation in the UK is for women between 25 and 49 years old to have a smear every 3 years, and then every 5 years until 64 years old. That’s 12 smears! Now I suspect there are a lot of women out there who hold no love for Georgios Papanikolaou and many will even go as far as saying the smear could only have been invented by a man! I get this!! I understand it is an unpleasant, embarrassing and often painful procedure to undergo. Screening however has been responsible for detecting many cases of precancerous cells and early cervical cancers which can then be cured by relatively minor surgical excision. Screening has undoubtedly saved many lives over the years with current estimates being that yearly in the UK 5000 deaths from cervical cancer are prevented by detecting abnormal cells before they develop into cancer.
Recently, there has been a change to cervical screening in the light of our knowledge about HPV being the cause. Nowadays most cervical smears are tested for HPV first and only by cytology if HPV is detected. Essentially this two-step approach uses the “over sensitive” HPV test to decide which samples need the more specific but time consuming cytology assessment. The HPV screen is good for saying a sample is negative whereas the cytology examination is good for saying a sample is positive; and together they are more accurate at determining true positive or negative tests.
Women still have to have the same number of smears; at the moment it is only the way the samples are tested that has changed.
If a samples tests positive for one of the high risk types of HPV then cytology will be performed. If the cervical cells look abnormal then the woman will need further examination by colposcopy. Colposcopy is a procedure where the cervix is directly visualised and further investigation or treatment including minor procedures can be undertaken. If there are no abnormal cells then a further smear will be done in 12 months’ time to see if there have been any changes, this is because 40% of women clear the infection naturally in 1 year, and 60% within 2 years, and not go on to develop precancerous cells. Cervical cancer won’t develop during this time; remember it is a screening test for precancerous cells not cancer itself. If HPV is still detected at 2 years then a colposcopy referral will be made.
I would strongly recommend anyone who wants to know more to visit the Jo’s Cervical Cancer Trust website as it has lots of excellent information presented in an easily understandable way.
How is HPV detected?
HPV in cervical smears is usually detected using a PCR based method for viral mRNA from specific high risk types of HPV as well as certain cancer genes. Locally we use a CE marked approved test that detects the presence of HPV by looking for mRNA from the highest risk types of HPV 16/17/45. In addition the test also looks for mRNA from two genes (E6 and E7) that encode proteins that can trigger cervical cells to become cancerous, known as oncogenes (from oncology, the science of cancer). The high risk types of HPV detected by our local test are 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68.
The published figures for the positive predictive value (PPV) of our local test for detecting precancerous cells is only about 7-20% which may seem very poor BUT the negative predictive value (NPV) is high at about 99.6% for more advanced cervical cell changes, which means that the false negative rate is 4 in 1000 patients and this is actually very good i.e. the test is very good at telling you haven’t got precancerous changes.
Screening tests are designed to have the best negative predictive value possible as they would rather over diagnose a condition and carry out further tests than miss the condition.
How might HPV vaccination change the cervical screening program?
Between 2007 and 2009 HPV vaccination started in the UK for girls aged 12-13 and now these girls are approaching the age for cervical screening. The vaccine is called Gardasil and contains proteins from HPV types 6/11/16/18; it does not contain live virus. In clinical trials it prevented 100% of 16 and 18 infections and it is expected to reduce cervical cancer rates by over 70%.
The way in which the HPV vaccine might affect the cervical screening program is firstly by making cervical cancer much less likely and secondly by altering the pre-test probability of a positive screening test. Let me explain further…
If a condition is very common in a population then a positive test that detects the condition is more likely to be a true positive and a negative test is more likely to be a false negative. Conversely if a condition is very uncommon then a positive test is likely to be a false positive whereas a negative test is likely to be a true negative.
In the case of cervical screening as cervical cancer becomes less common the better the screening test becomes at predicting negative results i.e. a negative test becomes more reliable. On the other hand the positive tests become more likely to be false positives. The effect of the screening program becomes better at excluding cervical cancer risk.
What might this mean for the future cervical screening program?
A recent paper by a team from Queen Mary University of London has looked at how HPV vaccine might theoretically influence how many cervical smears a woman might need to prevent cervical cancer from developing. They looked at numerous vaccination scenarios including effectiveness of the vaccine at preventing infection, the amount of the population vaccinated, potential cross protection to other types of HPV and possible effects of waning vaccine protection over time.
- Currently only 85% of eligible girls are immunised
- The new vaccine has a 90% success rate - up from 70% for the first vaccines
The main headline conclusion from the paper was that women who have been vaccinated against HPV only need 3 cervical screens, after a negative HPV test, during their lifetime to prevent a rise in cervical cancer rates. This has been translated by the mass media to be “all women only need three smears in their lifetime” but this is not what the paper actually says. The paper says VACCINATED women would only need three smears AFTER their first negative HPV test; unvaccinated women would still need the same frequency of screening that they currently get.
In addition, the paper comments on recent decisions by the Netherlands and Australia to move to five yearly screening of all women and the mathematical models suggest this will actually result in an increase in cervical cancer rates in unvaccinated women in these countries. That’s very worrying for most women and begs the question “is 5 yearly screening actually about saving money?”
So in the future, HPV vaccine may lead to a three prong approach to screening for cervical cancer. All patients will have a smear at 21 years old and be screened for HPV infection and vaccination status.
- Vaccinated HPV negative women might get three MORE lifetime cervical screens if they remain negative
- Vaccinated HPV positive women will get a repeat screen at 22 years of age and if this is positive go on for colposcopy whereas if it is negative on repeat testing they will go back to having three further lifetime smears
- Unvaccinated women will have the same 12 cervical screens that they currently get
It will be fascinating to see how this goes. A vaccine that prevents cancer is always going to be important and a vaccine that also saves a huge amount of unnecessary invasive investigation and anxiety as well as potentially saving a lot of money as well is of even more interest. So NO, you cannot cancel your smear… but our young girls may have less to endure in the future.
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