screening can identify potentially precancerous changes. Treatment of
high grade changes can prevent the development of cancer. In developed
countries, the widespread use of cervical screening programs has reduced
the incidence of invasive cervical cancer by 50% or more.
Human papillomavirus (HPV) infection is a necessary factor in the development of almost all cases of cervical cancer.HPV vaccines
effective against the two strains of HPV that currently cause
approximately 70% of cervical cancer have been licensed in the U.S,
Canada, Australia and the EU.Since the vaccines only cover some of the cancer causing ("high-risk")
types of HPV, women should seek regular Pap smear screening, even after
Cervix in relation to upper part of vagina and posterior portion of uterus.
Cervical cancer seen on a T2 weighted saggital MR image of the pelvis.
The early stages of cervical cancer may be completely asymptomatic.Vaginal bleeding,
contact bleeding or (rarely) a vaginal mass may indicate the presence
of malignancy. Also, moderate pain during sexual intercourse and vaginal
discharge are symptoms of cervical cancer. In advanced disease, metastases may be present in the abdomen, lungs or elsewhere.
Symptoms of advanced cervical cancer may include: loss of appetite,
weight loss, fatigue, pelvic pain, back pain, leg pain, single swollen
leg, heavy bleeding from the vagina, leaking of urine or faeces from the
vagina,and bone fractures.
Human papillomavirus (HPV) infection with high-risk types has been
shown to be a necessary factor in the development of cervical cancer.HPV DNA may be detected in virtually all cases of cervical cancer.Not all of the causes of cervical cancer are known. Several other contributing factors have been implicated.
Human papillomavirus infection
In the United States each year there are more than 6.2 million new
HPV infections in both men and women, according to the CDC, of which 10
percent will go on to develop persistent dysplasia or cervical cancer.
That is why HPV is known as the "common cold" of the sexually
transmitted infection world. It is very common and affects roughly 80
percent of all sexually active people, whether they have symptoms or
not. The most important risk factor in the development of cervical
cancer is infection with a high-risk strain of human papillomavirus. The virus cancer link works by triggering alterations in the cells of the cervix, which can lead to the development of cervical intraepithelial neoplasia, which can lead to cancer.
Women who have many sexual partners (or who have sex with men who had many other partners) have a greater risk.
More than 150 types of HPV are acknowledged to exist (some sources indicate more than 200 subtypes).
Of these, 15 are classified as high-risk types (16, 18, 31, 33, 35, 39,
45, 51, 52, 56, 58, 59, 68, 73, and 82), 3 as probable high-risk (26,
53, and 66), and 12 as low-risk (6, 11, 40, 42, 43, 44, 54, 61, 70, 72,
81, and CP6108). Types 16 and 18 are generally acknowledged to cause about 70% of
cervical cancer cases. Together with type 31, they are the prime risk factors for cervical cancer.
are caused by various strains of HPV which are usually not related to
cervical cancer. However, it is possible to have multiple strains at the
same time, including those that can cause cervical cancer along with
those that cause warts. The medically accepted paradigm, officially
endorsed by the American Cancer Society and other organizations, is that
a patient must have been infected with HPV to develop cervical cancer,
and is hence viewed as a sexually transmitted disease, but most women infected with high risk HPV will not develop cervical cancer.Use of condoms
reduces, but does not always prevent transmission. Likewise, HPV can be
transmitted by skin-to-skin-contact with infected areas. In males,
there is no commercially available test for HPV, although HPV is thought
to grow preferentially in the epithelium of the glans penis, and cleaning of this area may be preventative.
There has not been any definitive evidence to support the claim that
circumcision of the male partner reduces the risk of cervical cancer,
although some researchers say there is compelling epidemiological
evidence that men who have been circumcised are less likely to be
infected with HPV.
However, in men with low-risk sexual behaviour and monogamous female
partners, circumcision makes no difference to the risk of cervical
While the pap smear is an effective screening test, confirmation of the diagnosis of cervical cancer or pre-cancer requires a biopsy of the cervix. This is often done through colposcopy, a magnified visual inspection of the cervix aided by using a dilute acetic acid (e.g. vinegar) solution to highlight abnormal cells on the surface of the cervix.
Colposcopic impression, the estimate of disease severity based on the visual inspection, forms part of the diagnosis.
The naming and histologic classification of cervical carcinoma percursor lesions has changed many times over the 20th century. The World Health Organization classificationsystem was descriptive of the lesions, naming them mild, moderate or severe dysplasia or carcinoma in situ (CIS). The term, Cervical Intraepithelial Neoplasia (CIN) was developed to place emphasis on the spectrum of abnormality in these lesions, and to help standardise treatmentIt classifies mild dysplasia as CIN1, moderate dysplasia as CIN2, and
severe dysplasia and CIS as CIN3. More recently, CIN2 and CIN3 have been
combined into CIN2/3. These results are what a pathologist might report
from a biopsy.
Histologic subtypes of invasive cervical carcinoma include the following:Though squamous cell carcinoma is the cervical cancer with the most
incidence, the incidence of adenocarcinoma of the cervix has been
increasing in recent decades.
Gardasil, is a vaccine against HPV types 6, 11, 16 & 18 which is up to 98% effective.
Cervarix has been shown to be 92% effective in preventing HPV strains 16 and 18 and is effective for more than four years.
Together, HPV types 16 and 18 currently cause about 70% of cervical
cancer cases. HPV types 6 and 11 cause about 90% of genital wart cases.
HPV vaccines have also been shown to prevent precursors to some other
cancers associated with HPV.
HPV vaccines are targeted at girls and women of age 9 to 26 because
the vaccine only works if given before infection occurs; therefore,
public health workers are targeting girls before they begin having sex.
The vaccines have been shown to be effective for at least 4 to 6 years, and it is believed they will be effective for longer,however the duration of effectiveness and whether a booster will be needed is unknown.
The use of the vaccine in men to prevent genital warts, anal cancer, and interrupt transmission to women or other men is initially considered only a secondary market.
The high cost of this vaccine has been a cause for concern. Several
countries have or are considering programs to fund HPV vaccination.
Condoms offer some protection against cervical cancer.
Evidence on whether condoms protect against HPV infection is mixed, but
they may protect against genital warts and the precursors to cervical
cancer.They also provide protection against other STDs, such as HIV and
Chlamydia, which are associated with greater risks of developing
Condoms may also be useful in treating potentially precancerous
changes in the cervix. Exposure to semen appears to increase the risk of
precancerous changes (CIN 3), and use of condoms helps to cause these
changes to regress and helps clear HPV.One study suggests that prostaglandin in semen may fuel the growth of cervical and uterine tumours and that affected women may benefit from the use of condoms.
Carcinogens from tobacco
increase the risk for many cancer types, including cervical cancer, and
women who smoke have about double the chance of a nonsmoker to develop
Fruits and vegetables
Higher levels of vegetable consumption were associated with a 54% decrease risk of HPV persistence.
There is weak evidence to suggest a significant deficiency of retinol can increase chances of cervical dysplasia, independently of HPV
infection. A small (n~=500) case-control study of a narrow ethnic group
(native Americans in New Mexico) assessed serum micro-nutrients as risk
factors for cervical dysplasia. Subjects in the lowest serum retinol quartile were at increased risk of CIN I compared with women in the highest quartile.
However, the study population had low overall serum retinol,
suggesting deficiency. A study of serum retinol in a well-nourished
population reveals that the bottom 20% had serum retinol close to that
of the highest levels in this New Mexico sub-population.
Risk of type-specific, persistent HPV infection was lower among women reporting intake values of vitamin C in the upper quartile compared with those reporting intake in the lowest quartile.
HPV clearance time was significantly shorter among women with the highest compared with the lowest serum levels of tocopherols,
but significant trends in these associations were limited to infections
lasting </=120 days. Clearance of persistent HPV infection (lasting
>120 days) was not significantly associated with circulating levels
of tocopherols. Results from this investigation support an association
of micronutrients with the rapid clearance of incident oncogenic HPV
infection of the uterine cervix.
A statistically significantly lower level of alpha-tocopherol
was observed in the blood serum of HPV-positive patients with cervical
intraepithelial neoplasia. The risk of dysplasia was four times higher
for an alpha-tocopherol level < 7.95 mumol/l.
Higher folate status was inversely associated with becoming HPV
test-positive. Women with higher folate status were significantly less
likely to be repeatedly HPV test-positive and more likely to become
test-negative. Studies have shown that lower levels of antioxidants
coexisting with low levels of folic acid increases the risk of CIN
development. Improving folate status in subjects at risk of getting
infected or already infected with high-risk HPV may have a beneficial
impact in the prevention of cervical cancer.
However, another study showed no relationship between folate status and cervical dysplasia.
The likelihood of clearing an oncogenic HPV infection is significantly higher with increasing levels of lycopenes.A 56% reduction in HPV persistence risk was observed in women with the
highest plasma [lycopene] concentrations compared with women with the
lowest plasma lycopene concentrations. These data suggests that
vegetable consumption and circulating lycopene may be protective against
The widespread introduction of the Papanicolaou test, or Pap smear
for cervical cancer screening has been credited with dramatically
reducing the incidence and mortality of cervical cancer in developed
countries.Pap smear screening every 3–5 years with appropriate follow-up can reduce cervical cancer incidence by up to 80%. Abnormal Pap smear results may suggest the presence of cervical intraepithelial neoplasia
(potentially premalignant changes in the cervix) before a cancer has
developed, allowing examination and possible preventive treatment. If
premalignant disease or cervical cancer is detected early, it can be
monitored or treated relatively noninvasively, with little impairment of
Cervical cancer screening is typically recommended starting three years or more after first sex, or starting at age 21 to 25.
Recommendations for how often a Pap smear should be done vary from once
a year to once every five years, in the absence of abnormal results.
Guidelines vary on how long to continue screening, but well screened
women who have not had abnormal smears can stop screening about age 60
To take a Pap smear, the vagina is held open with a speculum,
the loose surface cells on the cervix are scraped using a specially
shaped spatula and a brush, and the cells are spread on a microscope
slide. At a laboratory the slide is stained, examined for abnormal cells and findings are reported.
Until recently the Pap smear has remained the principal technology
for preventing cervical cancer. However, following a rapid review of the
published literature, originally commissioned by NICE,liquid based cytology has been incorporated within the UK national
screening programme. Although it was probably intended to improve on the
accuracy of the Pap test, its main advantage has been to reduce the
number of inadequate smears from around 9% to around 1%. This reduces the need to recall women for a further smear.
Automated technologies have been developed with the aim of improving
on the interpretation of smears, normally carried out by
cytotechnologists. Unfortunately these on the whole have proven less
useful; although the more recent reviews suggest that generally they may
be no worse than human interpretation.
The HPV test is a newer technique for cervical cancer triage which detects the presence of human papillomavirus infection in the cervix. It is more sensitive
than the pap smear (less likely to produce false negative results), but
less specific (more likely to produce false positive results) and its
role in routine screening is still evolving. Since more than 99% of
invasive cervical cancers worldwide contain HPV, some researchers
recommend that HPV testing be done together with routine cervical
screening.But, given the prevalence of HPV (around 80% infection history among
the sexually active population) others suggest that routine HPV testing
would cause undue alarm to carriers, more unnecessary follow-up testing
and treatment. HPV testing along with cytology significantly increases
the cost of screening.
Various experimental techniques, such as visual inspection using acetic acid, sometimes with special lights (speculoscopy), or taking pictures for expert evaluation (cervicography)
have been evaluated as adjuncts to or replacements for Pap smear
screening, especially in countries where Pap smear screening is
prohibatively expensive. There are efforts to develop low cost HPV tests
which might be used for primary screening of older women in less
If a cone biopsy does not produce clear margins,one more possible treatment option for patients who want to preserve their fertility is a trachelectomy.
This attempts to surgically remove the cancer while preserving the
ovaries and uterus, providing for a more conservative operation than a
hysterectomy. It is a viable option for those in stage I cervical cancer
which has not spread; however, it is not yet considered a standard of
care,as few doctors are skilled in this procedure. Even the most experienced
surgeon cannot promise that a trachelectomy can be performed until
after surgical microscopic examination, as the extent of the spread of
cancer is unknown. If the surgeon is not able to microscopically confirm
clear margins of cervical tissue once the patient is under general
anesthesia in the operating room, a hysterectomy may still be needed.
This can only be done during the same operation if the patient has given
prior consent. Due to the possible risk of cancer spread to the lymph
nodes in stage 1b cancers and some stage 1a cancers, the surgeon may
also need to remove some lymph nodes from around the uterus for
A radical trachelectomy can be performed abdominally or vaginally and there are conflicting opinions as to which is better.
A radical abdominal trachelectomy with lymphadenectomy usually only
requires a two to three day hospital stay, and most women recover very
quickly (approximately six weeks). Complications are uncommon, although
women who are able to conceive after surgery are susceptible to preterm
labor and possible late miscarriage. It is generally recommended to wait at least one year before attempting to become pregnant after surgery. Recurrence in the residual cervix is very rare if the cancer has been cleared with the trachelectomy. Yet, it is recommended for patients to practice vigilant prevention and follow up care including pap screenings/colposcopy,
with biopsies of the remaining lower uterine segment as needed (every
3–4 months for at least 5 years) to monitor for any recurrence in
addition to minimizing any new exposures to HPV through safe sex practices until one is actively trying to conceive.
Early stages (IB1 and IIA less than 4 cm) can be treated with radical hysterectomy with removal of the lymph nodes or radiation therapy. Radiation therapy is given as external beam radiotherapy to the pelvis and brachytherapy
(internal radiation). Patients treated with surgery who have high risk
features found on pathologic examination are given radiation therapy
with or without chemotherapy in order to reduce the risk of relapse.
Larger early stage tumors (IB2 and IIA more than 4 cm) may be treated with radiation therapy and cisplatin-based chemotherapy, hysterectomy (which then usually requires adjuvant radiation therapy), or cisplatin chemotherapy followed by hysterectomy.
Advanced stage tumors (IIB-IVA) are treated with radiation therapy and cisplatin-based chemotherapy.
Prognosis depends on the stage of the cancer. With treatment, the 5-year relative survival rate
for the earliest stage of invasive cervical cancer is 92%, and the
overall (all stages combined) 5-year survival rate is about 72%. These
statistics may be improved when applied to women newly diagnosed,
bearing in mind that these outcomes may be partly based on the state of
treatment five years ago when the women studied were first diagnosed.
With treatment, 80 to 90% of women with stage I cancer and 50 to 65%
of those with stage II cancer are alive 5 years after diagnosis. Only 25
to 35% of women with stage III cancer and 15% or fewer of those with
stage IV cancer are alive after 5 years.
According to the International Federation of Gynecology and
Obstetrics, survival improves when radiotherapy is combined with
As the cancer metastasizes to other parts of the body, prognosis
drops dramatically because treatment of local lesions is generally more
effective than whole body treatments such as chemotherapy.
Interval evaluation of the patient after therapy is imperative.
Recurrent cervical cancer detected at its earliest stages might be
successfully treated with surgery, radiation, chemotherapy, or a
combination of the three. Thirty-five percent of patients with invasive
cervical cancer have persistent or recurrent disease after treatment.
Average years of potential life lost
from cervical cancer are 25.3 (SEER Cancer Statistics Review 1975-2000,
National Cancer Institute (NCI)). Approximately 4,600 women were
projected to die in 2001 in the US of cervical cancer (DSTD), and the
annual incidence was 13,000 in 2002 in the US, as calculated by SEER.
Thus the ratio of deaths to incidence is approximately 35.4%.
Regular screening has meant that pre cancerous changes and early
stage cervical cancers have been detected and treated early. Figures
suggest that cervical screening is saving 5,000 lives each year in the
UK by preventing cervical cancer. About 1,000 women per year die of cervical cancer in the UK.
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