Cervical cancer Totally Explained

Everything about Carcinoma Of The Cervix totally explained

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. Treatment consists of surgery (including local excision) in early stages and chemotherapy and radiotherapy in advanced stages of the disease. Pap smear 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 nearly all cases of cervical cancer. HPV vaccine effective against the two most common cancer-causing strains of HPV has been licensed in the U.S. and the EU. These two HPV strains together are currently responsible for approximately 70% of all cervical cancers. Experts recommend that women combine the benefits of both programs by seeking regular Pap smear screening, even after vaccination.

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.

Signs and symptoms

The early stages of cervical cancer may be completely asymptomatic. and bone fractures.

Causes

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, 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 or women who had many partners) have a greater risk.
   More than 250 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), 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're the prime risk factors for cervical cancer. Genital warts are caused by different HPV types and 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 most women infected with high risk HPV won't develop cervical cancer. Use of condoms reduces, but doesn't 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.

Cofactors

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, exposure to the hormonal drug diethylstilbestrol (DES) and a family history of cervical cancer.
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 don't outweigh the risks and/or consider the removal of healthy genital tissue from infants to be unethical as it can't be reasonably assumed that a male would choose to be circumcised. There hasn't been any definitive evidence to support the claim that male circumcision prevents cervical cancer, although some researchers say there's 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 cancer.

Diagnosis

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 (for example 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.

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:

Non-carcinoma malignancies which can rarely occur in the cervix include

melanoma

lymphoma Note that the FIGO stage doesn't 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 isn't to replace the original clinical stage.
For premalignant dysplastic changes, the CIN (cervical intraepithelial neoplasia) grading is used.

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
IVA - invades mucosa of bladder or rectum and/or extends beyond true pelvis
IVB - distant metastasis

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.
If a cone biopsy doesn't 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 hasn't spread; however, it isn't yet considered a standard of care, as few doctors are skilled in this procedure. Even the most experienced surgeon can't 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 isn't 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 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. Combination treatment has significant risk of neutropenia, anemia, and thrombocytopenia side effects. Hycamtin is manufactured by GlaxoSmithKline.

Prevention

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. 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.

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. Abnormal pap smear results suggest 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. 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. 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.

Preventive Vaccination

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. GlaxoSmithKline has developed a vaccine called Cervarix which has been shown to be 100% effective in preventing HPV strains 16 and 18 and is effective for more than four years. Cervarix has been approved some places and is in approval process elsewhere.
   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.
   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 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 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. Several countries have or are considering programs to fund HPV vaccination. In the United States, many states are preparing bills to handle issuing the HPV vaccine.

Condoms

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.

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.
   According to the International Federation of Gynecology and Obstetrics, survival improves when radiotherapy is combined with cisplatin-based chemotherapy.
   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.

Epidemiology

Worldwide, cervical cancer is the fifth most deadly cancer in women. It affects about 1 per 123 women per year and kills about 9 per 100,000 per year.
In the United States, it's only the 8th most common cancer of women. In 1998, about 12,800 women were diagnosed in the US and about 4,800 died.

In 1935, Syverton and Berry discovered a relationship between RPV (Rabbit Papillomavirus) and skin cancer in rabbits. (HPV is species specific and therefore can't 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 (for example Heins et al 1958) , 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. Specific viral subtypes implicated are HPV 16, 18, 31, 45 and others.

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