Cancer that forms in tissues of the cervix (the organ connecting the uterus and vagina). It is usually a slow-growing cancer that may not have symptoms but can be found with regular Pap tests (a procedure in which cells are scraped from the cervix and looked at under a microscope).

Estimated new cases and deaths from cervical (uterine cervix) cancer in the United States in 2009: New cases: 11,270 and Deaths: 4,070

What Causes Cervical Cancer?

Cervical cancer is almost certainly the result of some process that occurs during sexual intercourse. Over the years different components of the male ejaculate have been implicated. Nowadays, it would seem to be associated with infectious organisms, more specifically some strains of the human papillomavirus (HPV).

There are a number of risk factors associated with this form of cancer:

• Being a carrier of particular strains of the human papillomavirus (HPV) (the virus that causes genital warts) is the main risk factor.
• Being a smoker increases a woman's chances of developing cervical cancer.
• Having multiple sexual partners (or if your male partner has had multiple partners).
• A history of cancer of the vagina or uterus.
• A history of abnormal smear test results.
• Being HIV positive.
  

What are the symptoms of Cervical Cancer?

Some cancers of the cervix produce no symptoms. Most cancers of the cervix cause the woman to bleed after sex and to bleed between her periods. These can also be signs of a carcinoma in situ (CIN), which is a pre-cancerous condition, although the earlier pre-cancerous changes (dysplasia) do not cause any symptoms. This is why it is necessary to have regular smears to detect it.

If left untreated, the cancer spreads from the surface of the cervix into the deeper parts of the cervix and then out into the pelvic tissues, causing pain. Eventually the cancer may spread to the bladder, rectum and surrounding pelvic tissue, causing symptoms such as pain or bleeding from the rectum after a bowel movement or pain or difficulty urinating.

Prevention of Cervical Cancer

1. Vaccine

A vaccine that offers protection from the virus responsible for most cases of cervical cancer is the latest addition to the official childhood immunization schedule.

The cervical cancer vaccine (Gardasil) is the first vaccine approved by the Food and Drug Administration (FDA) designed to prevent a cancer. In the United States — where cervical cancer strikes about 10,000 women a year and causes nearly 4,000 deaths — the impact of the cervical cancer vaccine will be tremendous. Worldwide, the impact may be even greater. According to the World Health Organization, about 510,000 new cases of cervical cancer are reported each year.

The tragedy of cervical cancer is that it often strikes when a woman is still young. She may be trying to raise her family or maybe she hasn't had children yet. Cervical cancer treatment may make future fertility impossible.

• What does the cervical cancer vaccine do?
  Various strains of the human papillomavirus (HPV), which spreads through sexual contact, are responsible for most cases of cervical cancer. The cervical cancer vaccine specifically blocks two cancer-causing types of HPV — types 16 and 18 — to get at the root cause of the cancer. In essence, the cervical cancer vaccine stops cervical cancer before even the first step can begin.

The cervical cancer vaccine also blocks HPV types 6 and 11, which are not associated with cervical cancer but are associated with genital warts and mild Pap test abnormalities.

• When should the cervical cancer vaccine be given?
  The vaccine is recommended for girls ages 11 to 12, although it may be used in girls as young as age 9. This allows a girl's immune system to be activated before she's likely to encounter HPV. Vaccinating at this age also allows for the highest antibody levels. The higher the antibody levels, the greater the protection.

The vaccine is given as a series of three injections over a six-month period. The second dose is given two months after the first dose, followed four months later by the third dose.

Experts at the Centers for Disease Control and Prevention (CDC) recommend a catch-up immunization for girls and women ages 13 to 26 who haven't been vaccinated or who haven't completed the full vaccine series. By vaccinating this catch-up group, as well as the younger girls, we'll see the positive effects of the cervical cancer vaccine that much sooner.

• Why are three doses of the cervical cancer vaccine needed?
  We really don't know that three doses are necessary because we don't know what antibody levels provide adequate protection from HPV. In early clinical trials, researchers observed that the antibody levels in women continued to go up with each of the three doses of the vaccine. Since antibody levels inevitably fall once you stop getting a vaccine, it makes sense to start with high antibody levels to get the greatest HPV protection for the longest possible time — years or even decades.

Over time, we may find that three doses of the vaccine aren't necessary, or we may discover that a booster shot is needed years later. Those are details we just don't know right now.

• Does the vaccine offer benefits if you're already sexually active?
  Yes. In clinical trials, the vaccine was effective in a group of sexually active women age 26 or younger, some of whom had already been infected with one or more types of HPV. There's a caveat, however. The cervical cancer vaccine blocks HPV types 6, 11, 16 and 18, but only if you haven't been exposed to those particular types of HPV. The more sexual partners you've had, the greater your chance of having been exposed to multiple types of HPV — including HPV types 6, 11, 16 and 18.

Some experts encourage women ages 18 to 26 to review their sexual history with their doctors to determine if there's a reasonable chance of benefiting from the vaccine. Others support the CDC's recommendation of universal vaccination for women ages 18 to 26.

• Does the vaccine carry any health risks or side effects?
  The cervical cancer vaccine has proved to be remarkably safe. Over 16 million doses have been distributed in the U.S. The most common complaint is soreness at the injection site, the upper arm. Low-grade fever or flu-like symptoms also are common. Sometimes dizziness or fainting occurs after the injection, especially in adolescents. Overall, the effects are usually mild.

However, some serious side effects have been reported, including a severe allergic response (anaphylaxis); neurological conditions, such as paralysis, weakness and brain swelling; and death. The FDA continues to monitor all such reports. To date, almost all reports of such adverse side effects appear to have occurred around the time of vaccination by chance. They don't appear to be caused by the vaccination itself.

Monitoring is ongoing with this vaccine, as with all newer vaccines. Women and girls should remain seated in the clinic where they receive the vaccine for 15 minutes after the injection to reduce the risks of fainting or of an allergic reaction.

• Is the cervical cancer vaccine required for school enrollment?
  The cervical cancer vaccine is part of the routine childhood vaccines schedule. Whether or not a vaccine becomes a requirement for school is decided on a state-by-state basis. Remember, the greater the number of girls and women vaccinated, the greater the benefit we'll see from the cervical cancer vaccine.
• Will women still need to have Pap tests?
  Absolutely. And this is a really important point. The cervical cancer vaccine isn't intended to replace Pap tests. Routine screening for cervical cancer through regular pelvic exams and Pap tests remains an essential part of a woman's preventive health care.
• What can you do to protect yourself from cervical cancer if you're not in the recommended vaccine age group?
  HPV spreads through sexual contact. To protect yourself from HPV, use a condom every time you have sex. It's also important to limit your number of sexual partners. Not smoking helps, too. Smoking doubles the risk of cervical cancer.
• To detect cervical cancer in the earliest stages, see your doctor for regular pelvic exams and Pap tests. Seek prompt medical attention if you notice any signs or symptoms of cervical cancer — vaginal bleeding after sex, between periods or after menopause; foul-smelling watery or bloody vaginal discharge; pelvic pain; or pain during sex.

2. Screening

Pap Test:

Cervical cancer can usually be prevented if women are screened regularly with a test called the Pap test. Abnormal cells in the cervix and cervical cancer don’t always cause symptoms, especially at first. That’s why getting tested for cervical cancer is important, even if there are no symptoms. Most deaths from cervical cancer could be avoided if women had regular checkups with the Pap test.

The Pap test can find abnormal cells in the cervix. These cells may, over time, turn into cancer. This could take several years to happen.

Doctors recommend that women begin having regular Pap tests and pelvic exams at age 21, or within three years of the first time they have sexual intercourse – whichever happens first. National guidelines recommend that after a woman has a Pap test each year for three years in a row, and test results show there are no problems, she can then get the Pap test once every 2-3 years.

Liquid Based Cytology:

Liquid-based cytology is a new method of preparing cervical samples for cytological examination. Unlike the conventional ‘smear’ preparation, it involves making a suspension of cells from the sample and this is used to produce a thin layer of cells on a slide. The new intervention would thus form part of the process of population screening to reduce cervical cancer. In Brief,

• Liquid based cytology (LBC) is a new way of preparing cervical samples for examination in the laboratory
• LBC is as good as the conventional smear test. The sample is collected in a similar way to the Pap smear, using a special device (spatula) which brushes cells from the neck of the womb
• Rather than smearing the sample onto a microscope slide as happens with the Pap smear, the head of the spatula, where the cells are lodged, is broken off into a small glass vial containing preservative fluid, or rinsed directly into the preservative fluid.
• A thin layer of the cells is deposited onto a slide. The slide is examined in the usual way under a microscope by a cytologist.
  

LBC has slight advantage over the convetional Pap Smear test:

• reduce the number of inadequate smears (for example, the introduction of LBC at the pilot sites reduced the reported rate of inadequate smears from 9 per cent to 1-2 per cent.)
• reduce the pressure on a skilled workforce (fewer inadequate smears and clearer to read samples. Nationally, the workload would be reduced from 4.2 million slides per annum to 3.9 million slides per annum).
• reduce levels of anxiety in women who accept their invitation for cervical screening (quicker reporting time and a reduction in the number of women who are invited back for a repeat smear)
• save money overall

HPV DNA Test:

In women, human papillomaviruses (HPVs) can infect the cervix, vagina, vulva, urethra, or the area around the anus. More than 70 types of HPV have been identified, and are generally classified as high-risk or low-risk depending on their known association or lack of association with cancer and its precursor lesion, high-grade cervical intraepithelial neoplasia (CIN 2-3). Infection of the cervix with high-risk HPV types can be associated with cytological and histological changes that are detected by Pap screening, colposcopy, or biopsy. Low-risk HPV types 6 and 11 have been associated with the presence of genital warts, or condylomas, but have been linked infrequently with precancerous or cancerous cervical changes. There are many other low-risk HPV types that are not associated with genital warts or cervical cancer. The natural history of how HPV infection progresses to cancer, however, is not completely understood.

Historically, HPV 16 and HPV 18 have been regarded as high-risk cancer associated HPV types. HPV types 31, 33, and 35 have been demonstrated to have an intermediate association with cancer. This intermediate association is due to the fact that these types are more frequently detected in CIN 2-3 rather than in cancers. Therefore, cancers associated with the presence of these types are less common than cancers that are associated with high-risk HPV DNA types 16 and 18. These five HPV types together account for about 80% of cervical cancers. Additional high- and intermediate-risk HPV DNA types, including types 39, 45, 51, 52, 56, 58, 59 and 68, have been identified as the principal HPVs detectable in the remaining cancers.

Although current scientific literature suggests that persistent infection with high-risk HPV is the main risk factor for development of highgrade cervical neoplasia and cancer, apparent persistence may represent continuous infection with a single HPV type, with multiple HPV types, or reinfection. Nonetheless, women who are repeatedly Pap-negative and High-Risk-HPV negative appear to be at low risk for having or developing cervical precancerous lesions.
PRINCIPLE OF THE PROCEDURE
To date, HPV cannot be cultured in vitro, and immunological tests are inadequate to determine the presence of HPV cervical infection. Indirect evidence of anogenital HPV infection can be obtained through physical examination and by the presence of characteristic cellular changes associated with viral replication in Pap smear or biopsy specimens. Alternatively, biopsies can be analyzed by nucleic acid hybridization to directly detect the presence of HPV DNA.

HPV DNA Test (hc2 HPV DNA Test) reveals these high risk HPVs that cause the infection and provide vital information about the state of progression to the cervical disease. The hc2 HPV DNA Test using Hybrid Capture 2 technology is a nucleic acid hybridization assay with signal amplification that utilizes microplate chemiluminescent detection. Specimens containing the target DNA hybridize with a specific HPV RNA probe cocktail. The resultant RNA:DNA hybrids are captured onto the surface of a microplate well coated with antibodies specific for RNA:DNA hybrids. Immobilized hybrids are then reacted with alkaline phosphatase conjugated antibodies specific for the RNA:DNA hybrids, and detected with a chemiluminescent substrate. Several alkaline phosphatase molecules are conjugated to each antibody. Multiple conjugated antibodies bind to each captured hybrid resulting in substantial signal amplification. As the substrate is cleaved by the bound alkaline phosphatase, light is emitted that is measured as relative light units (RLUs) on a luminometer. The intensity of the light emitted denotes the presence or absence of target DNA in the specimen.

An RLU measurement equal to or greater than the Cutoff Value (CO) indicates the presence of HPV DNA sequences in the specimen. An RLU measurement less than the Cutoff Value indicates the absence of the specific HPV DNA sequences tested or HPV DNA levels below the detection limit of the assay.

It uses a cocktail of high risk (13 of them) and /or low risk (5 types together) HPV probe to determine the presence of high risk/low risk HPV.

HPV DNA by PCR:

Individual genotypes can be identifed by PCR or any other methods, most tests are analytically validated but may not be clinically validated. In the realm of infectious disease, it may be clinically important to have maximal analytic sensitivity for very small numbers of infectious particles like HIV or hepatitis C. In contrast, absolute analytic sensitivity for the smallest possible number of molecules of HPV-16 (or other types associated with risk of cervical cancer) is not a desirable result.

Simultaneously, though the analytical sensitivity of hc2 assay is 5,000 HPV genomes per test which is less sensitive than PCR based assay (identifies 10 viral copies), there are no standardized and well characterized PCR test protocols available for picking up high grade lesions clinically relevant from cancer management point of view. All that PCR does is to identify presence or absence of HPV in the specimen but that may or may not be clinical use as most infections clear spontaneously. Excessive analytic sensitivity of HPV molecular diagnostics can cause clinically nonspecific outcomes, ie, referral to colposcopy and possible biopsy in the absence of CIN 2 or CIN 3. If viral testing is too sensitive, the clinicians caring for the patient may come to consider the test results as false-positive because there may be no demonstrable evidence of disease cytologically, colposcopically, or histologically.

Therefore, from a clinical perspective, differentiation between high risk HPV or low risk HPV is of significance as it influences clinical management. The management decision is identical immaterial of which genotype is identified as long as it falls within the high or low group. Typically, a high risk result will lead to further tests to look for CIN lesions or a biopsy. A “low risk” result would certainly lead to a reassurance of the patient, perhaps a delayed repeat testing and definitive treatment of any cervical lesion through modalities such as cryotherapy (freezing), electro-coagulation (burning), electrosurgical excision (warts are removed by a high-frequency electric surgical knife), and laser therapy (warts are destroyed by laser).

Diagnosis

Colposcopy is a procedure to closely examine your cervix and vagina for signs of disease. During colposcopy, your doctor uses a special instrument called a colposcope.

Doctor may recommend colposcopy if the Pap test has returned abnormal results. If the doctor finds an unusual area of cells during colposcopy, a sample of tissue can be collected for laboratory testing (biopsy).

Many women experience anxiety before their colposcopy exams. Knowing what to expect during your colposcopy may help you feel more comfortable.

Why it's done:

Doctor may recommend colposcopy if a Pap test or pelvic exam revealed abnormalities. Colposcopy can be used to diagnose:

• Cervical cancer
• Genital warts
• Inflammation of the cervix (cervicitis)
• Precancerous changes in the cells of the cervix
• Precancerous changes in the cells of the vagina
• Vaginal cancer

Risks:

Colposcopy is a safe procedure that carries very few risks. Rarely, complications can occur, including:

• Heavy bleeding
• Infection
• Pelvic pain
  

Signs and symptoms that may indicate complications include:

• Bleeding that is heavier than what you typically experience during your period
• Chills
• Fever
• Severe abdominal pain
• Smelly vaginal discharge
  

Where it is done:

Colposcopy is usually done in a doctor's office and the procedure typically takes 10 to 20 minutes. You'll lie on your back on a table with your feet in supports, just as during a pelvic exam or Pap test.

The doctor places a metal speculum in your vagina. The speculum holds open the walls of your vagina so your doctor can see your cervix.

Your doctor positions the special magnifying instrument, called a colposcope, a few inches away from your vagina. A bright light is shown into your vagina and your doctor looks through the lens, as if using binoculars.

Your cervix and vagina are swabbed with cotton to clear away any mucus. Your doctor may apply a solution of vinegar or another type of solution to the area. This may cause a burning or tingling sensation. The solution helps highlight any areas of suspicious cells.

During the biopsy
If your doctor finds a suspicious area, a small sample of tissue may be collected for laboratory testing. To collect the tissue, your doctor uses a sharp biopsy instrument to remove a small piece of tissue. If there are multiple suspicious areas, your doctor may take multiple biopsy samples.

Results
Before you leave your colposcopy appointment, ask your doctor when you can expect the results. Also ask for a phone number you may call in the event you don't hear back from your doctor within a specified time.

The results of your colposcopy will determine whether you'll need any further testing and treatment.

Courtesy: www.cancer.org