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.
