Drugs Expert

Cervical cancer is malignant neoplasm 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.

The cervix is the lower part of the uterus (womb). It is sometimes called the uterine cervix. The body of the uterus (the upper part) is where a baby grows. The cervix connects the body of the uterus to the vagina (birth canal). The part of the cervix closest to the body of the uterus is called the endocervix. The part next to the vagina is the exocervix (or ectocervix). The 2 main types of cells covering the cervix are squamous cells (on the ectocervix) and glandular cells (on the endocervix). The place where these 2 cell types meet is called the transformation zone. Most cervical cancers start in the transformation zone.

Most cervical cancers begin in the cells lining the cervix. These cells do not suddenly change into cancer. Instead, the normal cells of the cervix first gradually develop pre-cancerous changes that turn into cancer. Doctors use several terms to describe these pre-cancerous changes, including cervical intraepithelial neoplasia (CIN), squamous intraepithelial lesion (SIL), and dysplasia. These changes can be detected by the Pap test and treated to prevent the development of cancer.

Cervical cancers and cervical pre-cancers are classified by how they look under a microscope. There are 2 main types of cervical cancers: squamous cell carcinoma and adenocarcinoma. About 80% to 90% of cervical cancers are squamous cell carcinomas. These cancers are from the squamous cells that cover the surface of the exocervix. Under the microscope, this type of cancer is made up of cells that are like squamous cells. Squamous cell carcinomas most often begin where the exocervix joins the endocervix.

Most of the remaining cervical cancers are adenocarcinomas. Adenocarcinomas are becoming more common in women born in the last 20 to 30 years. Cervical adenocarcinoma develops from the mucus-producing gland cells of the endocervix. Less commonly, cervical cancers have features of both squamous cell carcinomas and adenocarcinomas. These are called adenosquamous carcinomas or mixed carcinomas.

Although cervical cancers start from cells with pre-cancerous changes (pre-cancers), only some of the women with pre-cancers of the cervix will develop cancer. The change from cervical pre-cancer to cervical cancer usually takes several years — but it can happen in less than a year. For most women, pre-cancerous cells will go away without any treatment. Still, in some women pre-cancers turn into true (invasive) cancers. Treating all pre-cancers can prevent almost all true cancers.

Although almost all cervical cancers are either squamous cell carcinomas or adenocarcinomas, other types of cancer also can develop in the cervix. These other types, such as melanoma, sarcoma, and lymphoma, occur more commonly in other parts of the body.

What are the Causes and Risk Factors for Cervical Cancer?

When you get a diagnosis of cancer, it’s natural to wonder what may have caused the disease. Doctors cannot always explain why one woman develops cervical cancer and another does not. However, we do know that a woman with certain risk factors may be more likely than others to develop cervical cancer. A risk factor is something that may increase the chance of developing a disease.

Studies have found a number of factors that may increase the risk of cervical cancer. For example, infection with HPV (human papillomavirus) is the main cause of cervical cancer. HPV infection and other risk factors may act together to increase the risk even more:

• HPV infection: HPV is a group of viruses that can infect the cervix. An HPV infection that doesn’t go away can cause cervical cancer in some women. HPV is the cause of nearly all cervical cancers.
  HPV infections are very common. These viruses are passed from person to person through sexual contact. Most adults have been infected with HPV at some time in their lives, but most infections clear up on their own.
  Some types of HPV can cause changes to cells in the cervix. If these changes are found early, cervical cancer can be prevented by removing or killing the changed cells before they can become cancer cells.
  A vaccine for females ages 9 to 26 protects against two types of HPV infection that cause cervical cancer. The NCI fact sheet Human Papillomavirus (HPV) Vaccines: Questions and Answers has more information.
• Lack of regular Pap tests: Cervical cancer is more common among women who don’t have regular Pap tests. The Pap test helps doctors find abnormal cells. Removing or killing the abnormal cells usually prevents cervical cancer.
• Smoking: Among women who are infected with HPV, smoking cigarettes slightly increases the risk of cervical cancer.
• Weakened immune system (the body’s natural defense system): Infection with HIV (the virus that causes AIDS) or taking drugs that suppress the immune system increases the risk of cervical cancer.
• Sexual history: Women 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.
• Using birth control pills for a long time: 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.
• DES (diethylstilbestrol): DES may increase the risk of a rare form of cervical cancer in daughters exposed to this drug before birth. DES was given to some pregnant women in the United States between about 1940 and 1971. (It is no longer given to pregnant women.)

Having an HPV infection or other risk factors does not mean that a woman will develop cervical cancer. Most women who have risk factors for cervical cancer never develop it.

What are the Symptoms of Cervical Cancer?

Early cervical cancers usually don’t cause symptoms. When the cancer grows larger, women may notice one or more of these symptoms:

• Abnormal vaginal bleeding
  • Bleeding that occurs between regular menstrual periods
  • Bleeding after sexual intercourse, douching, or a pelvic exam
  • Menstrual periods that last longer and are heavier than before
  • Bleeding after going through menopause
• Increased vaginal discharge
  • Pelvic pain
  • Pain during sex

Infections or other health problems may also cause these symptoms. Only a doctor can tell for sure. A woman with any of these symptoms should tell her doctor so that problems can be diagnosed and treated as early as possible.

Detection and diagnosis of Cervical Cancer

Visual inspection to detect precancer or cancer

Visual inspection of the cervix, using acetic acid or Lugol’s iodine to highlight precancerous lesions so they can be viewed with the “naked eye”, shifts the identification of precancer from the laboratory to the clinic. Such procedures eliminate the need for laboratories and transport of specimens, require very little equipment and provide women with immediate test results. A range of medical professionals—doctors, nurses, or professional midwives—can effectively perform the procedure, provided they receive adequate training and supervision. As a screening test, VIA performs equal to or better than cervical cytology in accurately identifying pre-cancerous lesions. This has been demonstrated in various studies where trained physicians and mid level providers correctly identified between 45% and 79% of women at high risk of developing cervical cancer. By comparison, the sensitivity of cytology has been shown to be between 47 and 62%.It should be noted, however, that cytology provides higher specificity than VIA. Like cytology, one of the limitations of VIA is that results are highly dependant on the accuracy of an individual’s interpretation. This means that initial training and on-going quality control are of paramount importance.

VIA can offer significant advantages over Pap in low-resource settings, particularly in terms of increased screening coverage, improved follow up care and overall program quality. Due to the need for fewer specialized personnel and less infrastructure, training, and equipment, with VIA public health systems can offer cervical cancer screening in more remote (and less equipped) health care settings and can achieve higher coverage. Furthermore, providers can share the results of VIA with patients immediately, making it possible to screen and treat women during the same visit. This helps ensure that follow up care can be provided on the spot and reduces the number of women who may miss out on treatment because they are not able to return to the clinic at another time. In a “screen and treat” project in Peru, for example, only 9% of women who screened positive failed to receive treatment in the single-visit approach, compared with 44% of women who were lost to treatment using a multi-visit model.

VIA has successfully been paired with cryotherapy, a relatively simple and inexpensive method of treating cervical lesions that can be performed by primary care physicians and mid-level providers.

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 a dilute 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.

Pathologic types

Cervical intraepithelial neoplasia, the precursor to cervical cancer, is often diagnosed on examination of cervical biopsies by a pathologist. 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.

• squamous cell carcinoma (about 80-85%)
• adenocarcinoma (about 15% of cervical cancers in the UK)
• adenosquamous carcinoma
• small cell carcinoma
• neuroendocrine carcinoma

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

• melanoma
• lymphoma

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.

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

Methods of Treatment

Women with cervical cancer have many treatment options. The options are surgery, radiation therapy, chemotherapy, or a combination of methods.

The choice of treatment depends mainly on the size of the tumor and whether the cancer has spread. The treatment choice may also depend on whether you would like to become pregnant someday.

Your doctor can describe your treatment choices, the expected results of each, and the possible side effects. You and your doctor can work together to develop a treatment plan that meets your medical and personal needs.

Your doctor may refer you to a specialist, or you may ask for a referral. You may want to see a gynecologic oncologist, a surgeon who specializes in treating female cancers. Other specialists who treat cervical cancer include gynecologists, medical oncologists, and radiation oncologists. Your health care team may also include an oncology nurse and a registered dietitian.

Before treatment starts, ask your health care team about possible side effects and how treatment may change your normal activities. Because cancer treatments often damage healthy cells and tissues, side effects are common. Side effects may not be the same for each person, and they may change from one treatment session to the next.

At any stage of the disease, supportive care is available to relieve the side effects of treatment, to control pain and other symptoms, and to help you cope with the feelings that a diagnosis of cancer can bring.

You may want to talk to your doctor about taking part in a clinical trial, a research study of new treatment methods. See the section on Taking Part in Cancer Research.

Surgery

Surgery is an option for women with Stage I or II cervical cancer. The surgeon removes tissue that may contain cancer cells:

• Radical trachelectomy: The surgeon removes the cervix, part of the vagina, and the lymph nodes in the pelvis. This option is for a small number of women with small tumors who want to try to get pregnant later on.
• Total hysterectomy: The surgeon removes the cervix and uterus.
• Radical hysterectomy: The surgeon removes the cervix, some tissue around the cervix, the uterus, and part of the vagina.

With either total or radical hysterectomy, the surgeon may remove other tissues:

• Fallopian tubes and ovaries: The surgeon may remove both fallopian tubes and ovaries. This surgery is called a salpingo-oophorectomy.
• Lymph nodes: The surgeon may remove the lymph nodes near the tumor to see if they contain cancer. If cancer cells have reached the lymph nodes, it means the disease may have spread to other parts of the body.

The time it takes to heal after surgery is different for each woman. You may have pain or discomfort for the first few days. Medicine can help control your pain. Before surgery, you should discuss the plan for pain relief with your doctor or nurse. After surgery, your doctor can adjust the plan if you need more pain control.

After a radical trachelectomy, some women have bladder problems for a few days. The hospital stay usually is about 2 to 5 days.

After a hysterectomy, the length of the hospital stay may vary from several days to a week. It is common to feel tired or weak for a while. You may have problems with nausea and vomiting, and you may have bladder and bowel problems. The doctor may restrict your diet to liquids at first, with a gradual return to solid food. Most women return to their normal activities within 4 to 8 weeks after surgery.

After a hysterectomy, women no longer have menstrual periods. They cannot become pregnant.

When the ovaries are removed, menopause occurs at once. Hot flashes and other symptoms of menopause caused by surgery may be more severe than those caused by natural menopause. You may wish to discuss this with your doctor before surgery. Some drugs have been shown to help with these symptoms, and they may be more effective if started before surgery.

For some women, a hysterectomy can affect sexual intimacy. You may have feelings of loss that make intimacy difficult. Sharing these feelings with your partner may be helpful. Sometimes couples talk with a counselor to help them express their concerns.

Radiation therapy

Radiation therapy (also called radiotherapy) is an option for women with any stage of cervical cancer. Women with early stage cervical cancer may choose radiation therapy instead of surgery. It also may be used after surgery to destroy any cancer cells that remain in the area. Women with cancer that extends beyond the cervix may have radiation therapy and chemotherapy

Radiation therapy uses high-energy rays to kill cancer cells. It affects cells only in the treated area.

Doctors use two types of radiation therapy to treat cervical cancer. Some women receive both types:

• External radiation therapy: A large machine directs radiation at your pelvis or other tissues where the cancer has spread. The treatment usually is given in a hospital or clinic. You may receive external radiation 5 days a week for several weeks. Each treatment takes only a few minutes.
• Internal radiation therapy: A thin tube is placed inside the vagina. A radioactive substance is loaded into the tube. You may need to stay in the hospital while the radioactive source is in place (up to 3 days). Or the treatment session may last a few minutes, and you can go home afterward. Once the radioactive substance is removed, no radioactivity is left in your body. Internal radiation may be repeated two or more times over several weeks.

Side effects depend mainly on how much radiation is given and which part of your body is treated. Radiation to the abdomen and pelvis may cause nausea, vomiting, diarrhea, or urinary problems. You may lose hair in your genital area. Also, your skin in the treated area may become red, dry, and tender.

You may have dryness, itching, or burning in your vagina. Your doctor may advise you to wait to have sex until a few weeks after radiation treatment ends.

You are likely to become tired during radiation therapy, especially in the later weeks of treatment. Resting is important, but doctors usually advise patients to try to stay as active as they can.

Although the side effects of radiation therapy can be upsetting, they can usually be treated or controlled. Talk with your doctor or nurse about ways to relieve discomfort.

It may also help to know that most side effects go away when treatment ends. However, you may wish to discuss with your doctor the possible long-term effects of radiation therapy. For example, the radiation may make the vagina narrower. A narrow vagina can make sex or follow-up exams difficult. There are ways to prevent this problem. If it does occur, however, your health care team can tell you about ways to expand the vagina.

Another long-term effect is that radiation aimed at the pelvic area can harm the ovaries. Menstrual periods usually stop, and women may have hot flashes and vaginal dryness. Menstrual periods are more likely to return for younger women. Women who may want to get pregnant after radiation therapy should ask their health care team about ways to preserve their eggs before treatment starts.

Chemotherapy

For the treatment of cervical cancer, chemotherapy is usually combined with radiation therapy. For cancer that has spread to distant organs, chemotherapy alone may be used.

Chemotherapy uses drugs to kill cancer cells. The drugs for cervical cancer are usually given through a vein (intravenous). You may receive chemotherapy in a clinic, at the doctor’s office, or at home. Some women need to stay in the hospital during treatment.

The side effects depend mainly on which drugs are given and how much. Chemotherapy kills fast-growing cancer cells, but the drugs can also harm normal cells that divide rapidly:

• Blood cells: When chemotherapy lowers the levels of healthy blood cells, you’re more likely to get infections, bruise or bleed easily, and feel very weak and tired. Your health care team will check for low levels of blood cells. If your levels are low, your health care team may stop the chemotherapy for a while or reduce the dose of drug. There are also medicines that can help your body make new blood cells.
• Cells in hair roots: Chemotherapy may cause hair loss. If you lose your hair, it will grow back, but it may change in color and texture.
• Cells that line the digestive tract: Chemotherapy can cause a poor appetite, nausea and vomiting, diarrhea, or mouth and lip sores. Your health care team can give you medicines and suggest other ways to help with these problems.

Other side effects include skin rash, tingling or numbness in your hands and feet, hearing problems, loss of balance, joint pain, or swollen legs and feet. Your health care team can suggest ways to control many of these problems. Most go away when treatment ends.

Second opinion

Before starting treatment, you might want a second opinion about your diagnosis and treatment plan. Some people worry that the doctor will be offended if they ask for a second opinion. Usually the opposite is true. Most doctors welcome a second opinion. And many health insurance companies will pay for a second opinion if you or your doctor requests it.

If you get a second opinion, the doctor may agree with your first doctor’s diagnosis and treatment plan. Or the second doctor may suggest another approach. Either way, you have more information and perhaps a greater sense of control. You can feel more confident about the decisions you make, knowing that you’ve looked at your options.

It may take some time and effort to gather your medical records and see another doctor. In most cases, it’s not a problem to take several weeks to get a second opinion. The delay in starting treatment usually will not make treatment less effective. To make sure, you should discuss this delay with your doctor.

There are many ways to find a doctor for a second opinion. You can ask your doctor, a local or state medical society, a nearby hospital, or a medical school for names of specialists.

Nutrition and physical activity

It’s important for you to take care of yourself by eating well and staying as active as you can.

You need the right amount of calories to maintain a good weight. You also need enough protein to keep up your strength. Eating well may help you feel better and have more energy.

However, you may not feel like eating during or soon after treatment. You may be uncomfortable or tired. You may find that foods don’t taste as good as they used to. In addition, the side effects of treatment (such as poor appetite, nausea, vomiting, or mouth sores) can make it hard to eat well. Your doctor, a registered dietitian, or another health care provider can suggest ways to cope with these problems.

Research shows that people with cancer feel better when they stay active. Walking, yoga, swimming, and other activities can keep you strong and increase your energy. Exercise may reduce nausea and pain and make treatment easier to handle. It also can help relieve stress. Whatever physical activity you choose, be sure to talk to your doctor before you start. Also, if your activity causes you pain or other problems, be sure to let your doctor or nurse know about it.

Drugs rating:

Prevention

Primary Prevention

Vaccination

Gardasil, licensed and manufactured by Merck & Co. is a vaccine against HPV types 6, 11, 16 & 18. Gardasil is up to 98% effective. It is now on the market after receiving approval from the US Food and Drug Administration on June 8, 2006. Gardasil has also been approved in the EU.

GlaxoSmithKline has developed a vaccine called Cervarix which has been shown to be 92% 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 University of Queensland 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 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

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 cervical cancer.

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.

Smoking avoidance

Carcinogens from tobacco increase the risk for many cancer types, including cervical cancer, and women who smoke have about double the chance of a non-smoker to develop cervical cancer.

Nutrition

Fruits and vegetables

Higher levels of vegetable consumption were associated with a 54% decrease risk of HPV persistence. Consumption of papaya at least once a week was inversely associated with persistent HPV infection.

Vitamin A

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.

Vitamin C

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.

Vitamin E

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) 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. jojo

Folic acid

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.

Carotenoids

Higher circulating levels of carotenoids were associated with a significant decrease in the clearance time of type-specific HPV infection, particularly during the early stages of infection (120 days) was not significantly associated with circulating levels of carotenoids.

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 HPV persistence.

CoQ10

Women who had either CIN or cervical cancer had markedly lower levels of CoQ10 in their blood and in their cervical cells than the women who were healthy.

Secondary 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 2008 an estimated 3,870 women in the US will die of cervical cancer, and around 11,000 new cases are expected to be diagnosed.

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 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. Recommendations for how often a Pap smear should be done vary from once a year to once every five years. The ACS 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. Guidelines vary on how long to continue screening, but well screened women who have not had abnormal smears can stop screening about age 65 (USPSTF) to 70 (ACS). If premalignant disease or cervical cancer is detected early, it can be monitored or treated relatively noninvasively, and without impairing fertility.

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. The UK currently uses very different criteria for screening than that of America. In the UK a woman must be aged 25 or over in order to have a smear test and no older than 18 to receive the HPV vaccine. This means that the British 19-24 age group are not vaccinated currently, nor are they receiving screening.

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.

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. 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).

Prognosis

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 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. About 1,000 women per year die of cervical cancer in the UK.

Regular two-yearly Pap tests can reduce the incidence of cervical cancer by up to 90% in Australia, and save 1,200 Australian women dying from the disease each year.