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Cervical Cancer Cure - Cervical Cancer Medicine Drug
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Cervical cancer: malignant cancer of the cervix uteri or cervical
area. It may present with vaginal bleeding but symptoms may be absent
until the cancer is in its advanced stages, which has made cervical
cancer the focus of intense screening efforts using the Pap smear. In
developed countries, the widespread use of cervical screening
programs has reduced the incidence of invasive cervical cancer by 50%
or more.
Treatment consists of surgery (including local excision) in early
stages and chemotherapy and radiotherapy in advanced stages of the disease.
Human papillomavirus (HPV) infection is a necessary factor in the
development of nearly all cases of cervical cancer.[1] An effective
HPV vaccine against the two most common cancer-causing strains of HPV
has recently been licensed in the U.S. (see Vaccine section, below).
These two HPV strains together are responsible for approximately
70%[2][3] of all cervical cancers. Experts recommend that women
combine the benefits of both programs by seeking regular Pap smear
screening, even after vaccination.
Contents [hide]
1 Classification
2 Signs and symptoms
3 Causes
3.1 Human papillomavirus infection
4 Diagnosis
4.1 Biopsy procedures
4.2 Pathologic types
4.3 Staging
5 Treatment
6 Prevention
6.1 Awareness
6.2 Screening
6.3 Vaccination
7 Prognosis
8 Epidemiology
9 History
10 See also
11 References and Notes
12 External links
[edit] Classification
Cervical cancer is a carcinoma, typically composed of squamous cells,
and is similar in some respects to squamous cell cancers of the head
and neck and anus. All three of these diseases may be associated with
human papillomavirus infection.
[edit] Signs and symptoms
The early stages of cervical cancer may be completely
asymptomatic.[4] 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
feces from the vagina,[5] and bone fractures.
[edit] Causes
The American Cancer Society provides the following list of risk
factors for cervical cancer: human papillomavirus (HPV) infection,
smoking, HIV infection, chlamydia infection, dietary factors,
hormonal contraception, multiple pregnancies, use of the hormonal
drug diethylstilbestrol (DES) and a family history of cervical cancer.[6]
[edit] Human papillomavirus infection
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, leading to the development of cervical intraepithelial
neoplasia, leading to cancer.
Women who have many sexual partners (or who have sex with men or
women who had many partners) have a greater risk.[6][7]
More than 250 types of HPV are acknowledged to exist (some sources
indicate more than 200 subtypes).[8][9] 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),[10]
but even those may cause cancer. 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.[11]
Genital warts although caused by different HPV types have no relation
to cervical cancer.
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 not all women infected
with HPV develop cervical cancer.[12] Use of condoms does not always
prevent transmission. Likewise, HPV can be transmitted by
skin-to-skin-contact with infected areas. In males, HPV is thought to
grow preferentially in the epithelium of the glans penis, and
cleaning of this area may be preventative.
Despite the development of an HPV vaccine, some researchers argue
that routine neonatal male circumcision is an acceptable way to lower
the risk of cervical cancer in their future female sexual partners.
Others maintain that the benefits do not outweigh the risks and/or
consider the removal of healthy genital tissue from infants to be
unethical as it cannot be reasonably assumed that a male would choose
to be circumcised. There has not been any definitive evidence to
support the claim that male circumcision prevents 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.[13] However, in men with low-risk sexual behaviour
and monogamous female partners, circumcision makes no difference to
the risk of cervical cancer.[14]
[edit] Diagnosis
[edit] Biopsy procedures
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 an acetic acid (e.g. vinegar)
solution to highlight abnormal cells on the surface of the cervix.
Further diagnostic procedures are loop electrical excision procedure
(LEEP) and conization, in which the inner lining of the cervix is
removed to be examined pathologically. These are carried out if the
biopsy confirms severe cervical intraepithelial neoplasia.
[edit] Pathologic types
Cervical intraepithelial neoplasia, the precursor to cervical cancer,
is often diagnosed on examiniation of cervical biopsies by a
pathologist. Histologic subtypes of invasive cervical carcinoma
include the following:[15][16]
squamous cell carcinoma (about 80-85%)
adenocarcinoma
adenosquamous carcinoma
small cell carcinoma
neuroendocrine carcinoma
Non-carcinoma malignancies which can rarely occur in the cervix include
melanoma
lymphoma
IVA - invades mucosa of bladder or rectum and/or extends beyond true pelvis
IVB - distant metastasis
Note that the FIGO stage does not incorporate lymph node involvement
in contrast to the TNM staging for most other cancers.
For cases treated surgically, information obtained from the
pathologist can be used in assigning a separate pathologic stage but
is not to replace the original clinical stage.
For premalignant dysplastic changes, the CIN (cervical
intraepithelial neoplasia) grading is used.
[edit] Staging
Cervical cancer is staged by the International Federation of
Gynecology and Obstetrics (FIGO) staging system, which is based on
clinical examination, rather than surgical findings. It allows only
the following diagnostic tests to be used in determining the stage:
palpation, inspection, colposcopy, endocervical curettage,
hysteroscopy, cystoscopy, proctoscopy, intravenous urography, and
X-ray examination of the lungs and skeleton, and cervical conization.
The TNM staging system for cervical cancer is analogous to the FIGO stage.
Stage 0 - full-thickness involvement of the epithelium without
invasion into the stroma (carcinoma in situ)
Stage I - limited to the cervix
IA - diagnosed only by microscopy; no visible lesions
IA1 - stromal invasion less than 3 mm in depth and 7 mm or less in
horizontal spread
IA2 - stromal invasion between 3 and 5 mm with horizontal spread of 7
mm or less
IB - visible lesion or a microscopic lesion with more than 5 mm of
depth or horizontal spread of more than 7 mm
IB1 - visible lesion 4 cm or less in greatest dimension
IB2 - visible lesion more than 4 cm
Stage II - invades beyond cervix
IIA - without parametrial invasion, but involve upper 2/3 of vagina
IIB - with parametrial invasion
Stage III - extends to pelvic wall or lower third of the vagina
IIIA - involves lower third of vagina
IIIB - extends to pelvic wall and/or causes hydronephrosis or
non-functioning kidney
[edit] Treatment
Microinvasive cancer (stage IA) is usually treated by hysterectomy
(removal of the whole uterus including part of the vagina). For stage
IA2, the lymph nodes are removed as well. An alternative for patients
who desire to remain fertile is a local surgical procedure such as a
loop electrical excision procedure (LEEP) or cone biopsy.[17]
If a cone biopsy does not produce clear margins,[18] one more
possible treatment option for patients who want to preserve their
fertility is a trachelectomy.[19] 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,[20] 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 pathologic evaluation.
A radical trachelectomy can be performed abdominally[21] or
vaginally[22] and there are conflicting opinions as to which is
better.[23] 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.[24]
It is generally recommended to wait at least one year before
attempting to become pregnant after surgery.[25] Recurrence in the
residual cervix is very rare if the cancer has been cleared with the
trachelectomy.[20]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.
On June 15, 2006, the US Food and Drug Administration approved the
use of a combination of two chemotherapy drugs, hycamtin and
cisplatin for women with late-stage (IVB) cervical cancer
treatment.[26] Combination treatment has significant risk of
neutropenia, anemia, and thrombocytopenia side effects. Hycamtin is
manufactured by GlaxoSmithKline.
[edit] Prevention
[edit] Awareness
According to the US National Cancer Institute's 2005 Health
Information National Trends survey, only 40% of American women
surveyed had heard of human papillomavirus (HPV) infection and only
20% had heard of its link to cervical cancer.[27] In 2006 an
estimated 10,000 women in the US will be diagnosed with this type of
cancer and nearly 4,000 will die from it.[28]
[edit] Screening
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.[4] The pap smear suggests the presence of cervical
intraepithelial neoplasia (premalignant changes in the cervix) before
a cancer has developed, allowing for further workup. Recommendations
for how often a Pap smear should be done vary from once a year to
once every five years. The American Cancer Society recommends that
cervical cancer screening should begin approximately three years
after the onset of vaginal intercourse and/or no later than
twenty-one years of age.[29] If premalignant disease or cervical
cancer is detected early, it can be treated relatively noninvasively,
and without impairing fertility.
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.[11] 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.
HPV testing can reduce the incidence of grade 2 or 3 cervical
intraepithelial neoplasia or cervical cancer detected by subsequent
screening tests among women 32-38 years old according to a randomized
controlled trial.[30] The relative risk reduction was 41.3%. For
patients at similar risk to those in this study (63.0% had CIN 2-3 or
cancer), this leads to an absolute risk reduction of 26%. 3.8
patients must be treated for one to benefit (number needed to treat =
3.8). Click here to adjust these results for patients at higher or
lower risk of CIN 2-3.
[edit] Vaccination
Main article: HPV vaccine
Merck & Co. has developed a vaccine against four strains of HPV
(6,11,16,18), called Gardasil. It is now on the market after
receiving approval from the US Food and Drug Administration on June
8, 2006.[2] Gardasil is 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 use of the vaccine in men to prevent genital
warts and interrupt transmission to women is initially considered
only a secondary market. The high cost of this vaccine has been a
cause for concern. Gardasil has also been approved in the EU.<[31]
GlaxoSmithKline has developed a vaccine called Cervarix which
has been shown to be 100% effective in preventing HPV strains 16 and
18 and is 100% effective for more than four years.[32] These strains
together cause about 70% of cervical cancer cases. Cervarix should be
approved by year's end.[33]
Neither Merck & Co. nor GlaxoSmithKline invented the vaccine. The
vaccine's key developmental steps are claimed by the National Cancer
Institute in the US, the University of Rochester in New York,
Georgetown University in Washington, DC, Dartmouth College in
Hanover, NH, and the Queensland University in Brisbane, Australia.
Both Merck & Co. and GlaxoSmithKline have licensed patents from
all of these parties.[34]
In the Canadian provinces of Ontario, Prince Edward Island,
Newfoundland and Nova Scotia, free vaccinations to protect women
against HPV are slated to begin in September 2007 and will be offered
to girls 11-14 in age. Similar vaccination programs are also being
planned in British Columbia and Quebec.[35][36][37]
Australia has decided to fund the HPV vaccine under the National
Immunisation Program commencing in the 2007 school year.[38] In the
U.K. a similar free vaccination program is being considered,[39]
while in the United States, many states[attribution needed] are
preparing bills to handle issuing the HPV vaccine.[citation needed]
[edit] Prognosis
Prognosis depends on the stage of the cancer. 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.[40]
According to the International Federation of Gynecology and
Obstetrics, survival improves when radiotherapy is combined with
cisplatin-based chemotherapy.[41]
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.[42]
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.[43]
[edit] Epidemiology
Worldwide, cervical cancer is the fifth most deadly cancer in
women.[44] It affects about 1 per 123 women per year and kills about
9 per 100,000 per year.[citation needed]
In the United States, it is only the 8th most common cancer of women.
In 1998, about 12,800 women were diagnosed in the US and about 4,800
died.[4] Among gynecological cancers it ranks behind endometrial
cancer and ovarian cancer. The incidence and mortality in the US are
about half those for the rest of the world, which is due in part to
the success of screening with the Pap smear.[4]
In Great Britain, the incidence is 8.8/100,000 per year (2001),
similar to the rest of Northern Europe, and mortality is 2.8/100,000
per year (2003) (Cancer Research UK Cervical cancer statistics for
the UK). With a 42% reduction from 1988-1997 the NHS implemented
screening programme has been highly successful, screening the highest
risk age group (25-49 years) every 3 years, and those ages 50-64
every 5 years.
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.[45][46]
[edit] History
Epidemiologists working in the early 20th century noted that:
Cervical cancer was common in female sex workers.
It was rare in nuns, except for those who had been sexually active
before entering the convent. (Rigoni in 1841)
It was more common in the second wives of men whose first wives had
died from cervical cancer.
It was rare in Jewish women.[47]
In 1935, Syverton and Berry discovered a relationship between RPV
(Rabbit Papillomavirus) and skin cancer in rabbits. (HPV is species
specific and therefore cannot be transmitted to rabbits)
This led to the deduction that cervical cancer could be caused by a
sexually transmitted agent. Initial research in the 1950s and 1960s
put the blame on smegma (e.g. Heins et al 1958)[48] , but it wasn't
until the 1970s that human papillomavirus (HPV) was identified. A
description by electron microscopy was given earlier in 1949 and
HPV-DNA was identified in 1963. It has since been demonstrated that
HPV is implicated in virtually all cervical cancers.[3] Specific
viral subtypes implicated are HPV 16, 18, 31 and 45.
[edit] See also
Vaginal cancer
[edit] References and Notes
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^ Cite error: Invalid <ref> tag; no text was provided for refs
named pmid12674663
^ Heins Jr, HC; EJ Dennis, HR Pratt-Thomas (1958-10-01). "The
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[edit] External links
Cervical cancer at the Open Directory Project
Cervical cancer at the Yahoo! Directory
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