Women’s Health
Crush cervical cancer
– make prevention a priority
Cervical cancer has a high mortality, particularly in resource poor
countries, yet the disease can
be prevented with HPV vaccines and routine Pap smear screening. As the incidence
of cervical
cancer continues to increase in the Middle East, it is clear there is a need for
greater awareness
among healthcare practitioners, parents and ministries of health to do what they
can to reverse
this trend – be it advising their patients, ensuring their teenage daughters are
vaccinated or
implementing a nationwide Pap smear screening programme and ensuring school
girls are
routinely inoculated with HPV vaccine. Middle East Health reports.
Cervical cancer is preventable, yet it is the
second largest cause of mortality among
women in the Middle East and the incidence
of the disease appears to be increasing. In an
effort to reverse this trend several specialists in
the region are calling for greater awareness of
the disease among primary healthcare practitioners,
the implementation of screening
programmes by government bodies and for
greater public awareness of the disease.
Although recent incidence figures aren’t
readily available for countries in the Middle
East, worldwide there an estimated 500,000
cases a year, with approximately 270,000
deaths per year due to cervical cancer.
Extrapolating these figures indicates that
around 750 women die each day from the
disease worldwide and an estimated 25
women die each day in the Middle East
from the disease.
The figures should serve as a wake-up call
to doctors, women, parents and ministries of
health that this disease, which is fundamentally
preventable, is a major cause of
mortality.
Interestingly, there is a strong correlation
between the incidence of cervical cancer and
a country’s Gross Domestic Product (GDP),
with around 83% of global cervical cancer
cases occurring in resource-poor countries.
What is cervical cancer?
What exactly is cervical cancer? The US National Cancer Institute (NCI) defines
it
as a cancer that forms in tissues of the
cervix. It is usually a slow-growing cancer
that may not have symptoms, but can be
found with regular Pap smear tests (a procedure
in which cells are scraped from the
cervix and studied under a microscope).
Cervical cancer is almost always caused by
human papillomavirus (HPV) infection.
The disease begins on the surface of cervix
– the pre-invasive (or pre-cancer) stage. If
not treated it can invade more deeply into
the tissue of the cervix and becomes invasive
cervical cancer and is classified in
various stages depending on how deeply the
cancer has penetrated the tissue and to what
extent it has spread.
Human papillomavirus
There are more than 100 types of HPV – 40-
50 of which infect humans. Around 30 of
these can infect the genital area.
HPV is very common and highly contagious.
It is spread by sexual activity and skinto-
skin contact in the genital area. HPV types
16, 18, 31, 33, and 45 are considered high risk
and have been shown to be responsible for
about 85% of cervical cancers. Types 16 and
18 alone are thought to be responsible for
about 70% of cervical cancers.
The other HPV types cause warts on the
body. Most genital warts are associated with
HPV types 6 or 11.
Most HPV infections are asymptomatic or
subclinical and will clear up in a matter of
months with no treatment. However,
persistent infection with high-risk types of
HPV is considered the most important risk
factor for cervical neoplasia. High-risk types
are also known to cause anal or penile
cancer in males – typically homosexuals.
Dr Quek Swee Chong, Senior Consultant
and head of the pre-invasive and screening
unit at KK Women’s and Children’s
Hospital, Singapore, speaking to journalists
in Dubai in April, said around 80% of
women worldwide can expect to get an HPV
infection at some point in their lives. “In
many cases it will clear up within months
without the woman ever knowing she had
an infection.”
Dr Diane Harper, director of the
Gynecologic Cancer Prevention Research
Group at the University of Missouri, United
States, and a lead researcher in the development
of two HPV vaccines, was quoted as
saying during a presentation last year at the
4th International Public Conference on
Vaccination, in Reston, Virginia, US that
70% of all HPV infections generally resolve
themselves without treatment within a year.
Within two years, the number climbs to 90%.
Of the remaining 10% of HPV infections,
only half will develop into cervical cancer.
Risk factors
There are several risk factors for cervical
cancer. The US NCI lists the following:
● HPV infection: HPV is the cause of
nearly all cervical cancers.
● Lack of regular Pap tests: Cervical
cancer is more common among women
who don’t have regular Pap tests.
● Smoking: Among women who are infected
with HPV, smoking cigarettes slightly
increases the risk of cervical cancer.
● Weakened immune system: Infection
with HIV or taking drugs that suppress
the immune system increases the risk of
cervical cancer.
● Sexual history: Women who start sex at a
young age and who have had many sexual
partners have a higher risk of developing
cervical cancer. Also, a woman who has
had sex with a man who has had many sexual partners may be at higher risk of
developing
cervical cancer. In both cases,
the risk of developing cervical cancer is
higher because these women have a higher
risk of HPV infection.
Dr Chong noted, however, there should
be no stigma attached to being diagnosed
with an HPV infection as it does not
necessarily mean the women has had
multiple sexual partners. “It can take just
one sexual activity to transfer the virus.”
● Using birth control pills: Using birth
control pills for a long time (5 or more
years) may slightly increase the risk of
cervical cancer among women with HPV
infection. However, the risk decreases
quickly when women stop using birth
control pills.
● Having many children: Studies suggest
that giving birth to many children (5 or
more) may slightly increase the risk of
cervical cancer among women with HPV
infection.
Symptoms
Unfortunately early stage cervical cancer
does not show symptoms. Women with
advanced cervical cancer may experience
the following symptoms.
● Bleeding between regular menstrual
bleeding
● Bleeding after sexual intercourse
● Menstrual bleeding that lasts longer and
is heavier than previous bleeding
● Bleeding after menopause
● Increased vaginal discharge
● Pelvic pain
● Pain during sex
Prevalence Of cancers among women worldwide,
cervical cancer is the fifth biggest killer,
according the World Health Organisation.
The cancer with the highest mortality is
breast cancer, followed by lung, stomach,
colorectal and cervical cancers.
“Worldwide, breast cancer ranks as the
number one cancer, however in resource
poor countries cervical cancer is number
one,” Dr Chong pointed out, adding that
some 83% of cervical cancer cases occur in
resource poor countries, largely in the
southern hemisphere. “The reason for this is that women in these countries do
not have
access to regular Pap smear tests. In Europe
and the United States most women do have
regular Pap smears and the disease is
detected early and successfully treated.”
In the UAE, accurate figures of the prevalence
of cervical cancer are difficult to
obtain as there is no central cancer registry.
Speaking to Middle East Health Dr Saad
Ghazal-Aswad, a senior consultant gynaecological
oncologist and chairman of the
Obstetrics and Gynaecology Department at
Tawam Hospital, Al Ain, UAE, said that he
had noticed a significant increase in the
incidence of cervical cancer over the past
10 years.
“When I started working at Tawam hospital
in the late 1990s I used to see one cervical
cancer case every month and one pre-invasive
case about every 2 weeks. Now I see about 75-
100 cases per year [about 8 cases per month],
although these cases also include lower genital
tract neoplasia,” he said.
“My colleague in Saudi Arabia has experienced
a similar increase,” he noted.
According to Dr Falah Al Khatib, a radiation
oncologist at Tawam Hospital, there
were 41 cases of cervical cancer among UAE
nationals in the three-year period between
1999 – 2001. It was highest among women
between the ages of 40-49, followed by
women in the 50-59 age group. Sixty eight
percent presented with locally advanced
disease (stage IIb - Stage IVa). Widespread
metastases were observed in 7%.
Treatment
Standard treatments for cervical cancer
depend of the extent and stage of the cancer
and can involve surgery, radiotherapy or
chemotherapy.
Following an abnormal Pap smear a colposcopy is performed. Colpscopy is a
procedure where the cervix is illuminated
and magnified for diagnosis. If the disease is
at the pre-cancer stage it can be treated with
minor surgery and treatment is usually very
successful.
If the cancer is at stage 1 major surgery is
required, which can range from total
hysterectomy to radical hysterectomy and
even pelvic exenteration, where the cervix,
vagina, ovaries, and nearby lymph nodes are
removed.
At Stage 2, 3 or 4 cervical cancer is inoperable
and radiotherapy or chemotherapy is
required. “However this is often just palliative
care, as there is no cure,” noted Dr Chong.
Unfortunately, most cervical cancers are
detected at an advanced stage according to
Dr Chong. Most women who have cervical
cancer have not had Pap smear tests. Dr
Aswad corroborated this, saying in his experience
most cases of cervical cancer in the
UAE were presented at an advanced stage.
● The US NCI provides a comprehensive
cervical cancer treatment PDQ
(Physician Data Query) for healthcare
professionals online:
www.cancer.gov/
cancertopics/pdq/treatment/cervical/HealthProfessional
Prevention
Prevention is better than cure (or treatment)
as the old adage goes ... and cervical
cancer can be prevented.
Dr Chong emphasised: “It is the only
cancer to affect women that can be truly
prevented.”
There are two levels of prevention:
Primary prevention through the abstinence
of sex and inoculating against HPV with
vaccines before sexual activity begins.
Secondary prevention can be provided
through regular Pap smears, early detection
and treatment.
HPV vaccines
There are two HPV vaccines available.
Cervarix by GSK (Glaxo Smith Kline) and
Gardasil by MSD (Merck Sharp & Dohme).
Both are effective against HPV types 16 &
18, responsible for about 70% of cervical
cancers. Cervarix has been shown to
provide some protection against types 31,
33, & 45 responsible for around a further
15% of cervical cancers. Gardasil is also
effective against HPV types 6 & 11, which
can cause genital warts and there is
evidence that it protects againsts an additional
10 oncogenic HPV types that represent
a further 20% of cervical cancer cases.
For these vaccines to be effective they
should be given to women before they begin
sexual activity and it is generally recommended
they be given between the ages of 9
and 26 years. The US FDA approved Gardasil
for use in females ages 9 to 26 and approved
Cervarix for use in females ages 10 to 25. The
licensing varies from country to country.
“The younger the person the stronger
their immune reaction,” said Dr Aswad. “So
it is better to give the vaccine at a younger
age when they can develop a strong immunity
to the virus.”
It is recommended that the vaccine is
given in three doses over six months. Some countries have recently included
either Cervarix or Gardasil in their routine
vaccination programmes. In most countries
in the Middle East this remains under
discussion. However, the emirate of Abu
Dhabi has decided to routinely inoculate all
national girls at 17 years of age.
In the absence of the HPV vaccine being
included in a ministry of health-driven
vaccination programme the responsibility
falls on doctors – primary health care practitioners,
paediatricians and gynaecologists –
to inform parents about the vaccine and
urge them to have their daughters vaccinated
before they become sexually active,
said Dr Chong.
The duration of immunity provided by the
vaccines is not yet known. Research is being
conducted to find out how long protection
will last. Phase III clinical trials have shown
that Gardasil and Cervarix can provide
protection against HPV16 for 4 years.
Smaller studies have suggested that protection
is likely to last for longer than 4 years,
but it is not known if protection conferred
through vaccination will be lifelong. Dr
Chong noted that MSD and GSK predict
that immunity could last 15-20 years.
The US NCI notes that studies are being
carried out to find out whether booster
vaccines will be necessary to prolong the
immunity.
Vaccination in males
Gardasil may reduce the risk of genital warts
in males (HPV types 6 & 11 are responsible
for up to 90% of genital warts) and the
vaccine has been licensed for use in young
males in a number of countries.
● See: Lowy DR, Schiller JT (May 2006).
“Prophylactic human papillomavirus
vaccines”. The Journal of clinical investigation
116 (5): 1167–73. doi:10.1172/
JCI28607. PMID 16670757
Both vaccines are believed to reduce the
rates of penile and anal cancer in men,
which is also caused by HPV.
Pap smears
Regular Pap smears are recommended (every
one to three years) for all women who are
sexually active and should begin at least a
year after sexual activity begins. The Pap
test is essential to detect cervical cancers
and precancerous changes. By being tested
regularly it is highly likely that in the event
of the development of pre-cancer it will be
detected early and easily treated
The Pap test is not perfect, but the disease
develops slowly and in the event a single
Pap smear provides a false negative, by
having it performed regularly it should still
show any abnormal state that may have
developed, explained Dr Chong.
Current preventive vaccines reduce, but
do not eliminate the chance of getting
cervical cancer. Therefore, experts recommend
that women combine the benefits of
both programmes by seeking regular Pap
smear screening, even after vaccination.
Screening
In developed countries, the widespread use
of cervical Pap smear screening programmes
has reduced the incidence of invasive
cervical cancer by 50% or more.
In certain quarters in the Middle East there have been calls for governments to
implement Pap smear screening programmes
due to the apparent increasing incidence of
cervical cancer and because in many cases it
is presented as late stage cancer.
Dr Aswad noted that based on an analysis
of the epidemiological data that was available
for the incidence of cervical cancer in
the UAE, he and other experts in the field
were of the opinion that there were enough
cases to warrant a comprehensive government-
driven screening programme for
cervical cancer in the UAE.
At a National Workshop for Cervical
Cancer Prevention in Abu Dhabi in 2004,
senior physicians in the UAE, including Dr
Aswad, called on government to implement
such a programme and drew up a report
providing a comprehensive plan of action.
However, a screening programme has yet to
be implemented.
Vaccination programmes
National vaccination programmes with one
or the other of the HPV vaccines have been
introduced recently in a number of countries.
The implementation of such a programme is
a major undertaking on the part of government
both financially and organisationally.
Ideally the vaccine should be given to preteen
or early teen age girls and should be
done so while they are at school to facilitate
the organisational success of the programme.
At this stage in the GCC countries only the
Emirate of Abu Dhabi has implemented a
programme to vaccinate all 17-year-old
national and non-national girls with the
Gardasil quadrivalent HPV vaccine. In other
emirates and countries in the region such
vaccination programmes are apparently
under discussion. In the interim doctors are
urged to inform parents about the benefits of
the vaccination.
In Australia, commencing in 2007, the
federal government began funding a voluntary programme to make the Gardasil
vaccine available free of charge to women
aged 12–26 for a period of two years, with an
ongoing vaccination programme for 12- and
13-year-olds as part of the pre-existing high
school vaccination programme.
In the United Kingdom HPV vaccination
with Cervarix was introduced into the
national immunisation programme in
September 2008, for girls aged 12–13 across
the UK. A two-year catch up campaign
started in Autumn 2009 to vaccinate all girls
up to 18 years of age.
New Zealand, France, Sweden, South
Korea, Romania and several other countries
all have some form of state-funding for the
vaccine enabling girls to be vaccinated for
free or with state subsidy.
However, in some countries where there is
no state subsidy the vaccines remain out of
reach for many. For example, in Kenya,
where Cervarix and Gardasil are approved,
they cost in the region of 20,000 Kenyan
shillings (about US$260), which is more
than the average annual income for a family.
In conclusion
Speaking at a symposium at the 2nd annual
Middle East Obs-Gyne Congress in Dubai in
February this year, Dr Waleed Al Jassar,
Assistant Professor of Gynaecology Oncology
from the Faculty of Medicine at Kuwait
University, said: “Perhaps it is because of the
culture in the Middle East or perhaps it is
because cervical cancer has no symptoms, but
more attention needs to be given to this
disease and its preventative measures.
“In the case of cervical cancer, we are
faced with a deadly disease which results
from an untreated virus, a virus that can be
prevented with a vaccine.”
He called on doctors to gain a clear picture
of how they can help women reduce the risk
of contracting HPV and the resulting cancer.
Also speaking at the symposium, Dr
Muna El Kuwari, Director of Primary
Healthcare for the UAE Ministry of
Health, said: “With the advent of vaccines
against cervical cancer, we now have
powerful new tools to reduce cervical
cancer and save women’s lives.”
Dr Chong emphasised that there was a
major effort worldwide, which is gaining
momentum, to increase awareness of
cervical cancer, “because we have the ability
to prevent it”.
Further Reading
The following papers are Open Access. No
subscription is required.
■ Are treatments for cervical precancerous
lesions in less-developed countries safe enough
to promote scaling-up of cervical screening
programs? A systematic review.
Eric Chamot et al
BMC Women’s Health 2010, 10:11
doi:10.1186/1472-6874-10-11
■ Prevalence of various Human Papillomavirus (HPV) genotypes among women
who are subjected to routine Pap smear test in
Bushehr city (South west of Iran)2008-2009
Keivan Zandi et al
Virology Journal 2010, 7:65
doi:10.1186/1743-422X-7-65
■ A randomized controlled trial of Human Papillomavirus (HPV) testing for cervical
cancer screening: trial design and preliminary
results (HPV FOCAL Trial)
Gina S Ogilvie et al
BMC Cancer 2010, 10:111
doi:10.1186/1471-2407-10-111
■ Type-specific incidence, clearance and
predictors of cervical human papillomavirus
infections (HPV) among young women: a
prospective study in Uganda
Cecily Banura et al
Infectious Agents and Cancer 2010, 5:7
doi:10.1186/1750-9378-5-7
Date
of upload: 20th June 2010
