SCREENING FOR CERVICAL CANCER

Cervical cancer is the second commonest cancer in women in the world. In 2012 528,000 new cases of cervical cancer occurred, out of which 266,000 died as compared to 26-37 women who died out of 100,000 in 1933. Now in 2008 7.5 women died. Thanks to the cervical cancer test invented by a Greek gynaecologist George Papanicolaou in 1928. This was a most important story in public health. The test in short is called a Pap test. 

He studied these cells on his wife and said these changes occur due to infection irritation and hormone changes which occur without any symptoms. These were called, CIN 1 (cervical intraepthelial neoplasia) mild dysplasia, or CIN 2 moderate dysplasia and CIN 3, which stood for severe dysplasia, high grade epithelial neoplasia or carcinoma in situ.

This further led to cervical cancer10 -20 years later. This led to the study of cervical cells called the “PAP” test prepared from the cervix. Cervix is the lowermost part of the Uterus. On examination the cervix is exposed and cells are collected from the cervix by a brush, spread on a glass slide fixed and sent to the laboratory then studied by a scientist called a cytologist. All this required a set up of laboratories, technicians and scientists. If indicated this is further followed up by another test called a colposcopy by a gynaecologist in which the cervix is examined by a microscope, biopsied, depending on the findings it is either followed up or treated. From 1960 onward random pap tests or opportunistic pap tests were performed. This gradually was bringing down the incidence of cervical cancer. In 1976 a German scientist suggested that a viral infection called Human Papilloma Virus (HPV) is involved in its causation. 

In 1980 Hausen identified HPV 16 and 18. He won a noble prize for these findings. In 1995 it was determined that HPV 16 and 18 are certainly Oncogenic, and are responsible for cervical cancer. In the next 1-3 years they started to test for these viruses in the cervical samples. 1996 -1999 the collection of the cervical sample was done in a liquid medium. In 2006 a DNA test was developed for HPV. At this time co-testing started; that is a PAP test as well as DNA for HPV. Things were progressing fast HPV vaccines also came on the market. Vaccination was introduced in 2007. Originally there were 2 vaccines, Gardiasil 4-valent (This worked against 4 viruses ,16, ;18 , 11,6)and Cervarix (2 valent). As of 2014, in some countries they have Gardiasil 9-valent, this means it prevents against 9 HPV viruses 6, 11, 16, 18, 31,33,45,55 58. It is suggested that the vaccine is given at the age of 11 to12 years, in the first year of secondary school both to boys and girls.

 3 injections are required; within 6 months, the first

Injection; the second 2 months later and the last within the initial 6months. The protection is not 100%, and there are some side effects, like in any other vaccine, but overall the benefit is tremendous.

There are several types of cervical cancers one of them is called neuroendocrine (tumour from a combination of nervous tissue and hormone tissues) this is very rare, only about 1.2 % of all cervical cancers. It is not preventable by any means.

In many countries around the world including Australia and, New Zealand, USA and Austria, national cervical screening programmes were introduced in the early 90’s. In this programme the cervical screening started at the age of 18 to 65 or even earlier if sexually active, this was done every 1-3 years depending on the country. If an abnormality was found these women had further tests and were treated. The treatments offered were, diathermy, cryotherapy, leep (loop electrosurgical excision) ,letz (loop excision of an area of the cervix called  transformation zone)  laser vaporisation, cone biopsy and even hysterectomy. This was not good for their reproductive future. National screening programmes

have  reduced the risk of cervical cancer in many countries by almost 50%.

Vaccination programmes started in 2006-2007. It is hoped this will reduce the risk of cervical cancer further.  Vaccination does not prevent every cervical cancer. It is effective against those which are caused by HPV16 and HPV18. Now with the use of Gardiasil 9-valent it will be effective against many more. It is found that there are 100 different types of HPV. 14 of these have been found to affect the genital tracks (causing cancer) both in men and women.

Recent research has found that the risk of cervical cancer has been markedly reduced in women over 25 years of age but not so in younger women, although the cervical cancer vaccination was started in 2007, it is already showing a reduction of cervical dysplasia abnormalities and it will reduce them further as time goes on as more and more individuals will be vaccinated. The risk of cervical cancer in the age group of 20 -24 is very small 1.3 cases out of a population of 100,000, may be one death per year as compared to  7 per 100,000 in the age group of 25 -39 ,or over. Cervical screening programs have not shown any further reduction in cervical cancer in the age group of 20 -24.  There is no doubt that HPV is the main culprit in the causation of cervical cancer. It takes 10 -20 years for the changes in the cervix to develop after the infection in naturally well immunised healthy women and 5-10 years in compromised women. The other factors which add to occurrence of cervical cancer are early sexual activity, multiple partners by a woman or even her partner, early and multi parity, tobacco, poor hygiene, and poor nutrition. 99% of HPV infection clears by itself, even the changes caused in the cervix

heal.  However if a woman takes birth control pills for a long time, hormones in the pill may change its ability to clear HPV hence taking oral contraceptives is a risk factor for cervical cancer(CC). HPV is the main offender. It has been estimated that HPV positive women showed cervical abnormalities in 1% of women tested as compared to women tested by cytology alone in 0.1%. HPV vaccination gives further protection but it is not effective if you are already infected.

What is HPV? It is a cancer causing virus, which is sexually transmitted by skin to skin contact; hence it cannot be protected by condoms. WHO recommends it causes 5.2 % of cervical cancers world wide. AS already pointed out there are only 1.3 cases of CC in per 100,000 women may be one death in the age group of 20 -24, as compared to 6.7 in the age group of 25 -49. So far scientists have identified more than 100 types of HPV, about 14 of these effect our genital tract, cervix, vagina, and vulva. It also causes cancer of the rectum, throat and penis cancer in men. HPV is also known to cause some cancers in the brain.

In view of great success of immunisation programmes, and understanding of HPV being the main culprit for causation of cervical cancer, many countries are changing the cervical cancer screening programmes, in Australia which is one of the first countries this will start on first of Dec 2017.It has been confirmed that starting cervical cancer screening at 25 is safe. The best protection for women under 25 is vaccination; worldwide in developed nations almost all girls and boys are being (Vaccinated) protected.

From now on (1 of Dec 2017) the government in Australia will send women an invitation on their 25th birthday vaccinated or not .The sample from the cervix will be collected without much trauma by a clinician. In fact many women will be allowed to do their own vaginal swab, this is sent in a liquid medium to the laboratory. This will have a great cultural and social benefits so that a lot of women will be tested, who so far are reluctant to have this done. Sample is generally equally good they do not have to face a clinician, and spend money. This sample will be tested for HPV, if negative; the women only have to return after 5 years up to the age of 70 then they are offered an exit test at 75. The risk of CC is almost nil, as long as they are HPV negative. It is such a relief for women also in time and cost savings. In Australia this will be very good for women living in Torres Strait islands and aborigines who normally never have the test done, although they are 4 times more likely to get CC. If you are already on the old 2 yearly test, you will have this new test within 3 months of the time when your test is due. If you have never had a test done for CC screening, join the new programme. If the test was positive, they test the geno type, to test for virus 16 and 18, if so cervical cytology is also performed on the same sample and if required the woman is referred to a gynaecologist for colposcopy (examination of the cervix by a microscope by a specially trained Gynaecologist) and treatment if required. So almost all tests are done on one sample, and treated the same day. In severe cases 6 months later a pap test and colposcopy is repeated. One year later a PAP test and HVP test is done. 24 months after treatment HPV and PAP test is done again if both are negative, twice in sequence a woman can have 2 yearly check ups. This makes the screening very simple and inexpensive both for women and their countries they live in. In fact many countries like Canada and Austria are hoping that cervical cancer can be totally eliminated by using Vaccination and HPV testing. CC will become a thing of the past. If the HPV test was not convincingly negative it is repeated after one year. If a woman is symptomatic e.g. having discharge, blood staining, pain, bleeding on intercourse, irregular bleeding, weight loss, she should be investigated urgently for CC and STD’s, irrespective of her age. There are some cases reported where some women are dying of cervical cancer under the age of 25.

In USA cervical screening programmes are slightly different. Under 21 years of age they are no longer screened whether they were vaccinated or not. 21 -29 PAP every 3 years.  Many members ACOG prefer a co test meaning HPV test and cervical smear as well. 30 -39 PAP test every 3 years or a co test every 5 years. Over 65 there is no need to test if they have never had a CIN or the last co test was negative performed with 5 years.

In many western countries the cervical cancer deaths are as low as 1.8 per 100,000 women per year. Where as in developing countries they can be as high 75 per 100,000 (Melanesia, Southern and Middle Africa). Main burden of cervical cancer deaths falls on low and middle income countries (LMIC), in 2012 when 266,000 women died in the world, 230,158 died in developing countries. In LMIC, countries the work on prevention of cervical cancer is still in progress. In some LMIC countries they are trying to use vaccination. Some countries are using one vaccine instead of three, further tests have shown that they provide adequate protection and you can vaccinate three times as many girls. PAP tests are not feasible in these counties due to social economic and technical reasons. These women are subjected to a visual test.

The diseased parts of the cervix do not take the iodine stain.

Application with 3-5% accetic acid or lugols iodine. Visual inspection of the cervix and vagina is fairly informative. These have sensitivity of 80% and with logols iodine specificity of 92%. 

This can be difficult in older women and also depends on the training of the test performer. If these tests are positive these women are treated with cold coagulation (cryo-therapy),if it is found to be more significant, they are referred for proper assessment and treatment.  They are also referred for molecular testing (these are newer types of tests that are under research) depending on the health resources. WHO recommends targeting women at age 30 for HPV testing. I personally somehow feel, it could be earlier, as life in these countries begins early. These measures in LMIC are being helpful little by little. It is estimated that when a vaccine is introduced in the western world, it usually takes 10-30 years before it can be used in low and middle income countries and the reasons for this are many and varied but the principle one is the cost factor.

The current change in screening for cervical cancer, which is a totally preventable disease, is due to our discovery of HPV as a causative factor.

Thanks to Hausen for this discovery. It was confirmed that HPV infection causes cervical cancer 10- 15years after the infection. So if we test for HPV we can totally exclude CC. Hence these changes in screening for cervical cancer will start at the age of 25 and will be required every 5 years. Women can collect their own samples and triage can be done on the same day with the same sample. This will save 20% more lives. Some countries hope, like many other diseases, cervical cancer will be a thing of the past.

95% of HPV and changes in the cervix clear by themselves, this will change so much in convenience and cost for women and countries. All the changes introduced in LMIC are also improving their mortality. There are now 71 countries in the world who are offering free HPV vaccination to school girls like any other vaccines and hopefully this in time will be global.