Zanmbeel

Monday, October 15, 2007

Polycystic ovary syndrome (PCOS)

DEFINITION — Polycystic ovary syndrome (PCOS) is a chronic condition that causes irregular menstrual periods and elevated levels of androgens (male hormones) in women. The elevated androgen levels can sometimes cause excessive facial hair growth, acne, and/or male-pattern hair thinning. The condition occurs in about 5 to 10 percent of women.

Although PCOS is not completely reversible, there are a number of treatments that can reduce or minimize bothersome symptoms. Most women with PCOS are able to lead a normal life without significant complications.

CAUSE — The cause of PCOS is not completely understood. It is believed that abnormal levels of the pituitary hormone LH and high levels of male hormones (androgens) interfere with normal function of the ovaries. To explain how these hormones cause symptoms, it is helpful to understand the normal menstrual cycle.

The brain (including the pituitary gland), ovaries, and uterus normally follow a sequence of events once per month; this sequence helps to prepare the body for pregnancy. Two hormones, follicle stimulating hormone (FSH) and luteinizing hormone (LH), are made by the pituitary gland. Two other hormones, progesterone and estrogen, are made by the ovaries.

During the first half of the cycle, small increases in FSH stimulate the ovary to develop a follicle (cyst) that contains an egg (oocyte). The follicle produces rising levels of estrogen, which cause the lining of the uterus to thicken and the pituitary to release a very large amount of LH. This midcycle "surge" of LH causes the egg to be released from the ovary (called ovulation, show figure 1).

After ovulation, the ovary produces both estrogen and progesterone, which prepare the uterus for possible implantation and pregnancy. In women with PCOS, multiple follicles (cysts) may develop. The follicles are unable to grow to a size that would trigger ovulation. Therefore, small follicles (4 to 9 mm in diameter) accumulate in the ovary, hence the term polycystic ovaries. None of these small follicles are capable of initiating ovulation nor can they release an egg. As a result, the levels of estrogen, progesterone, LH, and FSH become imbalanced.

Androgens are normally produced by the ovaries, the adrenal gland, and probably from other sources as well. Examples of androgens include testosterone, androstenedione, dehydroepiandrosterone (DHEA), and DHEA sulfate (DHEA-S). It is thought that androgens (male-type hormones) become increased in women with PCOS because of the high levels of LH, but also because of high levels of insulin that are usually seen with PCOS (see "Insulin abnormalities" below).

SIGNS AND SYMPTOMS — The changes in hormone levels, described above, cause the classic symptoms of PCOS, including absent or irregular menstrual periods, abnormal hair growth or loss, acne, weight gain, and difficulty becoming pregnant. (See "Patient information: Hair loss in men and women (androgenetic alopecia)").

Signs and symptoms of PCOS usually begin around the time of puberty, although some women do not develop symptoms until adulthood. Because hormonal changes vary from one woman to another, patients with PCOS may have mild to severe acne, facial hair growth, or scalp hair loss.

Menstrual irregularity — If ovulation does not occur, the lining of the uterus (called the endometrium) does not uniformly shed and regrow as in a normal menstrual cycle. Instead, the endometrium becomes thicker and may shed irregularly, which can result in heavy and/or prolonged bleeding. Irregular or absent menstrual periods can increase a woman's risk of endometrial overgrowth (called endometrial hyperplasia) or even endometrial cancer.

Women with PCOS usually have fewer than six to eight menstrual periods per year. Some women have normal cycles during puberty, which may become irregular as weight gain occurs.

Weight gain and obesity — PCOS is associated with gradual weight gain and obesity in about one-half of women. For some women with PCOS, obesity develops at the time of puberty.

Hair growth and acne — Male-pattern hair growth (hirsutism) may be seen on the chin, neck, sideburn area, chest, and upper abdomen. Acne is a skin condition that causes oily skin and blockages in hair follicles, leading to pimples.

Insulin abnormalities — PCOS is associated with elevated levels of insulin in the blood. Insulin is a hormone that is produced by specialized cells within the pancreas; insulin regulates blood glucose levels. When blood glucose levels rise (after eating, for example), these cells produce insulin to help the body use glucose for energy. If glucose levels do not decline in response to normal levels of insulin, the pancreas produces additional insulin. Excess production of insulin is called hyperinsulinemia. When increased levels of insulin are required to maintain normal glucose levels, a person is said to be insulin resistant. When the blood glucose levels are not completely controlled with increased amounts of insulin, the person is said to have impaired glucose tolerance. If blood glucose levels continue to rise despite increased insulin levels, the person is said to have type 2 diabetes.

These conditions are diagnosed with blood tests. (See "Patient information: Diabetes mellitus, type 2").

Insulin resistance and hyperinsulinemia can occur in both normal-weight and overweight women with PCOS. Among women with PCOS, up to 35 percent of obese women develop impaired glucose tolerance by age 40, while up to 10 percent of obese women develop type 2 diabetes. The risk of these conditions is much higher in women with PCOS compared to women without PCOS.

Infertility — If a woman with PCOS has difficulty becoming pregnant after six to 12 months of trying to conceive, an evaluation of both partners is needed to determine the cause of infertility. (See "Patient information: Evaluation of the infertile couple").

Heart disease — Women who are obese and who also have insulin resistance or diabetes have an increased risk of coronary artery disease, the narrowing of the arteries that supply blood to the heart. Both weight loss and treatment of insulin abnormalities can decrease this risk. Other treatments (eg, cholesterol lowering medications, treatments for high blood pressure) may also be recommended. (See "Patient information: High cholesterol and lipids (hyperlipidemia)" and see "Patient information: High blood pressure treatment").

Sleep apnea — Sleep apnea is a condition that causes brief spells where breathing stops (apnea) during sleep. Patients with this problem often experience fatigue and daytime sleepiness. In addition, there is evidence that people with untreated sleep apnea have an increased risk of cardiovascular problems such as high blood pressure, heart attack, abnormal heart rhythms, or stroke. This risk may be due to the wide fluctuations in heart rate and blood pressure that occur in people with sleep apnea.

Sleep apnea may occur in up to 30 percent of women with PCOS. The condition can be diagnosed with a sleep study, and several treatments are available. (See "Patient information: Sleep apnea").

DIAGNOSIS — There is no single test for diagnosing PCOS. A woman may be diagnosed with PCOS based upon her signs and symptoms and blood tests. Expert groups have determined that a woman must have all of the following to be diagnosed with PCOS: Irregular menstrual periods caused by anovulation or irregular ovulation Evidence of elevated androgen levels. The evidence can be based upon signs (hirsutism, acne, or male pattern balding) or blood tests (high serum androgen concentrations) No evidence of other causes of elevated androgen levels or irregular periods (eg, congenital adrenal hyperplasia, androgen-secreting tumors, or hyperprolactinemia)

Blood tests are usually recommended to determine if another condition is the cause of a person's signs and/or symptoms. Blood tests for pregnancy, prolactin level, thyroid stimulating hormone (TSH), and follicle stimulating hormone (FSH) may be recommended.

If PCOS is confirmed, the blood glucose level and cholesterol levels are usually measured; these tests are best done before the first meal of the day. Other glucose tests, called oral glucose tolerance testing and hemoglobin A1C, may also be recommended. In women with moderate to severe hirsutism (excess hair growth), blood tests for testosterone and DHEA-S may be recommended.

All women who are diagnosed with PCOS should be monitored by a healthcare provider. Symptoms of PCOS may seem minor and annoying and treatment may seem unnecessary. However, untreated PCOS can increase a woman's risk of other health problems over time.

TREATMENTS

Oral contraceptives — Oral contraceptives (OCs) are the most commonly used treatment for establishing normal menstrual periods in women with PCOS. OCs protect the uterine lining from a precancerous or cancerous condition by inducing a monthly menstrual period, and are also effective for treating hirsutism and acne.

Women with PCOS occasionally ovulate, and oral contraceptives are useful in providing protection from pregnancy. Although an OC allows for bleeding once per month, this does not mean that the PCOS is "cured"; irregular cycles generally return when the OC is stopped. (See "Patient information: Menstrual cycle disorders (Absent and irregular periods)").

Oral contraceptives decrease the body's production of androgens, and anti-androgen drugs (such as spironolactone) decrease the effect of androgens. Both treatments can lessen and slow hair growth. Oral contraceptives and antiandrogens can also reduce acne, although some women should consult a healthcare provider about the need for prescription skin treatments (eg, medicated lotions) or oral antibiotics. (See "Patient information: Acne").

Before prescribing an oral contraceptives, a clinician will perform an examination or a blood test to be certain that a woman is not pregnant. If a woman hasn't had a period for six weeks or longer, her clinician may first prescribe a hormone (eg, Provera®) to induce a menstrual period. Side effects — Some women who take oral contraceptives (not just those with PCOS) may notice amenorrhea (lack of monthly bleeding) or breakthrough bleeding (bleeding that occurs at the irregular time of the month). Breakthrough bleeding usually resolves after a few menstrual cycles.

Many women worry that they will gain weight on the pill. This is not a concern with the currently available low-dose pills. Some women develop nausea, breast tenderness, and bloating after beginning the pill, but these symptoms usually resolve after two or three months.

The pill is safe and effective, although it slightly increases the risk of blood clots in the legs or lungs, although this is a rare complication in young, healthy women who do not smoke. The risk is higher in women older than 35 years and in smokers. (See "Patient information: Hormonal methods of birth control").

Progestin — Another method to treat menstrual irregularity is to take a hormone called progestin (eg, Provera®) for 10 to 14 days every one to three months. This will cause a period in almost all women with PCOS, but it does not help with the cosmetic concerns (hirsutism and acne) and does not prevent pregnancy. It does reduce the risk of uterine cancer.

Hair treatments — Excess hair can be removed by shaving or use of depilatories, electrolysis, or laser therapy. Many women worry that these treatments cause hair to grow faster, although this is not true. (See "Patient information: Causes and treatment of hirsutism"). Hair loss can be treated with medications in some situations, although medications are not usually as effective in women with hormonally-related hair loss as they are in men. Other options include hair replacement and wigs. (See "Patient information: Hair loss in men and women (androgenetic alopecia)").

Weight loss — Weight loss is one of the simplest, yet most effective, approaches for managing insulin abnormalities, menstrual irregularities, and other symptoms of PCOS. For example, many overweight women with PCOS who lose 5 to 10 percent of their body weight notice that their periods become more regular. Weight loss can often be achieved with a program of diet and exercise.

There are a number of options available for obesity. These options are identical to those recommended for women without PCOS, and include diet and exercise, weight loss medications, and weight loss surgery. (See "Patient information: Diet and health" and see "Patient information: Weight loss treatments").

Weight loss surgery may be an option for severely obese women with PCOS. Significant amounts of weight can be lost after surgery, which can restore normal menstrual cycles, reduce high androgen levels and hirsutism, and reduce the risk of type 2 diabetes. (See "Patient information: Weight loss surgery").

Metformin — Metformin (Glucophage®) is medication that improves the effectiveness of insulin produced by the body. It is sometimes used to treat the insulin abnormalities associated with PCOS. This medication can decrease the ovary's production of androgens and reestablish the body's normal hormone balance. The end result is that some signs and symptoms of PCOS improve.

Metformin is usually prescribed for the treatment of diabetes. In preliminary studies, metformin helps restore normal menstrual cycles in approximately 50 percent of women with PCOS. Blood androgen levels sometimes decrease, but there may not be much improvement in hirsutism or acne. In addition, metformin does not prevent pregnancy. In fact, it can stimulate ovulation; another method of pregnancy prevention is recommended to women who do not want to become pregnant.

Metformin may also help with weight loss. Although metformin is not a weight-loss drug, some studies have shown that women with PCOS who are on a low-calorie diet lose more weight when metformin is added. If metformin is used, it is essential that diet and exercise are also part of the recommended regimen because the weight that is lost in the early phase of metformin treatment may be regained over time.

Treatment of infertility — If tests determine that lack of ovulation is the cause of infertility, several treatment options are available, including clomiphene and gonadotropin therapy. These treatments work best in women who are not obese. A summary of treatment options is shown in table 1 (show table 1).

The primary treatment for women who are unable to become pregnant and who have PCOS is weight loss. Even a modest amount of weight loss may cause the woman to begin ovulating normally. In addition, weight loss can improve the effectiveness of other infertility treatments.

Clomiphene is a medication that stimulates the ovaries to release one or more eggs. It triggers ovulation in about 80 percent of women with PCOS, and about 50 percent of these women will become pregnant. (See "Patient information: Infertility treatment with clomiphene (Clomid® or Serophene®)").

Several studies have shown that metformin increases the effectiveness of clomiphene in producing ovulation. However, it is unknown if this drug is safe during pregnancy, so the current recommendation is to stop metformin once pregnancy is achieved.

If a woman does not ovulate or is unable to conceive with clomiphene, gonadotropin therapy may be recommended. Gonadotropins are hormones (LH and FSH) that are given as a daily injection under the skin for 7 to 10 days. Ovulation occurs in almost all women with PCOS who use gonadotropin therapy; approximately 60 percent of these women become pregnant.

WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

From UpToDate — This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

From other sources — A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine

(www.nlm.nih.gov/medlineplus/healthtopics.html)
The Hormone Foundation

(www.hormone.org/public/polycystic.cfm, available in English and Spanish)
U.S. Department of Health and Human Services

(www.4woman.gov/faq/pcos.htm)
American Academy of Family Physicians

(www.familydoctor.org)
The Nemours Foundation

(http://kidshealth.org/teen/sexual_health/girls/pcos.html)

[1-4]

Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Ehrmann, DA, Cavaghan, MK, Barnes, RB, et al. Prevalence of impaired glucose tolerance and diabetes in women with Polycystic Ovary Syndrome. Diabetes Care 1999; 22:141.
2. Adams, J, Polson, DW, Franks, S. Prevalence of polycystic ovaries in women with anovulation and idiopathic hirsutism. BMJ 1986; 293:355.
3. Huber-Buchholz, MM, Carey, DG, Norman, RJ. Restoration of reproductive potential by lifestyle modification in obese polycystic ovary syndrome: Role of insulin sensitivity and luteinizing hormone. J Clin Endocrinol Metab 1999; 84:1470.
4. Nestler, JE, Jakubowicz, DJ, Evans, WS, Pasquali, R. Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. N Engl J Med 1998; 338:1876.

Polycystic ovary syndrome (PCOS)

Chronic pelvic pain in women

DEFINITION — Chronic pelvic pain is defined as pain that occurs below the umbilicus (belly button) that lasts for at least six months. It may or may not be associated with menstrual periods. Chronic pelvic pain is not a disease, rather, it is a symptom that can be caused by several different conditions.

CAUSES — A variety of gynecologic, gastrointestinal, and systemic disorders, can cause chronic pelvic pain.

Gynecologic causes — Gynecologic causes are thought to be the cause of chronic pelvic pain in about 20 percent of women. Some of the gynecologic causes of pelvic pain include:

Endometriosis — The tissue lining the inside of the uterus is called the endometrium (show figure 1). Endometriosis is a condition in which endometrial tissue is also present outside of the uterus. Some women with endometriosis have no symptoms, while others experience marked discomfort and pain and may have problems with fertility. (See "Patient information: Endometriosis" and see "Patient information: Evaluation of the infertile couple").

Chronic pelvic inflammatory disease — Pelvic inflammatory disease is an infection caused by a sexually transmitted organism. Occasionally, it is caused by a previous ruptured appendix or scarring resulting from previous pelvic surgery. It can involve the uterus, ovaries, and fallopian tubes (which link the ovaries and uterus) (show figure 1). Pelvic inflammatory disease can cause pain, abnormal uterine bleeding, and symptoms of infection such as fever and chills.

Other causes — Non-gynecologic causes of chronic pelvic pain may be related to the digestive system, urinary system, or to pain in the muscles and nerves in the pelvis:

Irritable bowel syndrome — Irritable bowel syndrome is a gastrointestinal condition characterized by chronic abdominal pain and altered bowel habits (such as loose stools, more frequent bowel movements with onset of pain, and pain relieved by defecation) in the absence of any specific cause. (See "Patient information: Irritable bowel syndrome").

Painful bladder syndrome and interstitial cystitis — Painful bladder syndrome and interstitial cystitis are the terms given to inflammation of tissues in the bladder and surrounding nerves and muscles that is not caused by infection. Symptoms usually include the need to urinate frequently (frequency) and a feeling of urgently needing to urinate (urgency). Some women with painful bladder syndrome have lower abdominal or pelvic pain in addition to urinary tract symptoms.

Diverticulitis — A diverticulum is a sac-like protrusion that sometimes forms in the muscular wall of the colon (or intestine). Diverticulitis occurs when diverticula become inflamed. This usually causes abdominal pain; nausea and vomiting, constipation, diarrhea, and urinary symptoms can also occur. (See "Patient information: Diverticular disease").

Pelvic floor pain — The muscles of the pelvic floor can sometimes become shortened, tight and tender; this is called pelvic floor dysfunction. The pelvic floor includes muscles that attach to the pelvic bones and sacrum (lower part of the spine). Normally, these muscles function to support the hips and pelvic organs. It is not clear why this problem develops, but symptoms may include pelvic pain, pain with urination, constipation, pain with intercourse, or frequent/urgent urination. Pelvic floor dysfunction can be diagnosed by a clinician by applying pressure to the muscles in the vagina and/or rectum; muscles that feel tight, tender, or band-like indicate that pelvic floor dysfunction could be contributing to pelvic pain.

Fibromyalgia — Fibromyalgia is one of a group of chronic pain disorders that affect connective tissue structures, including muscles, ligaments, and tendons. It is characterized by widespread muscle pain (or "myalgia") and tenderness in certain areas of the body. Women with fibromyalgia may also experience fatigue, sleep disturbances, headaches, and mood disturbances such as depression and anxiety. (See "Patient information: Fibromyalgia").

DIAGNOSIS — Because a number of different conditions can cause chronic pelvic pain, it is sometimes difficult to pinpoint the specific cause.

History and physical examination — A thorough history and a physical examination of the abdomen and pelvis are essential components of the work-up for women with pelvic pain. In particular, the examination should include the lower back, abdomen, hips, and pelvis (internal examination).

Laboratory tests, including a white blood cell count, urine analysis, tests for sexually transmitted infections, and a pregnancy test may be recommended, depending upon the results of the physical examination.

Pelvic ultrasound — Some diagnostic procedures may also be helpful in identifying the cause of chronic pelvic pain. As an example, a pelvic ultrasound examination is accurate in detecting pelvic masses, including ovarian cysts (sometimes caused by ovarian endometriosis) and uterine fibroids. However, ultrasound is not helpful in the diagnosis of irritable bowel syndrome, diverticulitis, or painful bladder syndrome.

Laparoscopy — A surgical procedure called a laparoscopy may be helpful in diagnosing some causes of chronic pelvic pain such as endometriosis and chronic pelvic inflammatory disease. Laparoscopy is a procedure that is often done as a day surgery. Most women are given general anesthesia to induce sleep and prevent pain. A thin telescope with a camera is inserted through a small incision just below the navel. Through the telescope, the surgeon can see the contents of the abdomen, especially the reproductive organs. If the laparoscopy is normal, the physician can then focus the diagnostic and treatment efforts on non-gynecologic causes of pelvic pain.

If the laparoscopy is abnormal (eg, areas of endometriosis or abnormal tissue are seen) these areas may be treated or biopsied during the procedure.

TREATMENT — Chronic pelvic pain due to a gynecologic condition is often treated medically. In some cases, however, surgery may be the treatment of choice.

Medical treatment — Medication may be prescribed once laboratory and imaging tests suggest the pain is due to a gynecologic condition. Drugs that may be used include: Nonsteroidal anti-inflammatory medications such as ibuprofen Oral contraceptive pills prescribed as monthly cycles or as "long cycles." When prescribed as long cycles, a woman takes the active pill continuously for three to four months followed by one week off the pill. Doxycycline, an antibiotic used to treat some causes of pelvic inflammatory disease. Medications called gonadotropin releasing hormone (GnRH) agonist analogues used to treat endometriosis.

Physical therapy — Pelvic floor physical therapy (PT) is often helpful for women with tight and tender pelvic muscles. This type of PT aims to release the tightness in these muscles by manually "releasing" the tightness; treatment is directed to the muscles in the vagina, hips, thighs, and lower back. Physical therapists who perform this type of PT must be specially trained.

Pain management clinics — If medications are not effective in treating the pain, a woman may be referred to a medical practice specializing in pain management. Pain services utilize multiple treatment modalities including Acupuncture Biofeedback and relaxation therapies Nerve stimulation devices Injection of tender sites with local anesthesia medication

Psychological counseling may be offered to help women manage the pain. Pain services can help women who have become dependent on narcotics for pain management.

Surgical treatment — A few causes of gynecologic pelvic pain can be treated surgically. For example, some women benefit from surgical removal of their endometriosis.

Hysterectomy may alleviate chronic pelvic pain, especially when it is due to uterine disorders such as adenomyosis or fibroids. However, pain can persist even after hysterectomy, particularly in younger women (those less than 30) and in women with a history of chronic pelvic inflammatory disease or pelvic floor dysfunction. Hysterectomy is not a good choice for the management of chronic pelvic pain in women who have not completed their family. (See "Patient information: Abdominal hysterectomy" and see "Patient information: Vaginal hysterectomy").

Surgery to cut some of the nerves in the pelvis has also been studied as a treatment for chronic pelvic pain. However, this approach has not proven to be effective for most women.

WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine

(www.nlm.nih.gov/medlineplus/healthtopics.html)
The International Pelvic Pain Society

(www.pelvicpain.org)
The Mayo Clinic

(www.mayoclinic.com)
U.S. Department of Health and Social Services

(www.4woman.gov, search for pelvic pain)

[1-3]

Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Mathias, SD, Kuppermann, M, Liberman, RF et al. Chronic pelvic pain: prevalence, health-related quality of life, and economic correlates. Obstet Gynecol 1996; 87:321.
2. Scialli, AR. Evaluating chronic pelvic pain. A consensus recommendation. Pelvic Pain Expert Working Group. J Reprod Med 1999; 44:945.
3. Flor, H, Fydrich, T, Turk, DC. Efficacy of multidisciplinary pain treatment centers: a meta-analytic review. Pain 1992; 49:221.

Treatment of abnormal Pap smears

INTRODUCTION — Several treatments are available for women with cervical abnormalities, often referred to as dysplasia, CIN (cervical intraepithelial neoplasia) or CIS (carcinoma in situ). Treatments including cryosurgery (freezing), laser (high-energy light), and excision (surgical removal of the abnormal area).

A separate topic review discusses the testing used to diagnose these types of cervical abnormalities, including Pap smears or ThinPrep cytology, human papillomavirus (HPV) testing, and colposcopy. (See "Patient information: Screening for cervical cancer").

CHOOSING THE BEST TREATMENT — Abnormal pap smears are treated by identifying the area of abnormal cervical tissue and removing it to prevent worsening or spread to other areas of the cervix. There are two main types of treatment for cervical abnormalities: those that destroy the abnormal area (called ablative therapy) and those that remove the abnormal areas (called excisional therapy). Some abnormalities are best treated with one type of treatment while others can be treated with either type, depending upon the patient and physician's preference. There are some classes of abnormalities that can be followed without treatment, if the physician and patient are willing.

Excisional therapy — Excisional therapies include loop electrosurgical excision procedures (LEEP, also called large loop excision of the transformation zone (LLETZ), laser conization, and cervical conization procedures. Most clinicians prefer excisional therapy (see "Excision" below).

Excisional therapy is recommended when the extent or type of cervical abnormality is not clear based upon colposcopy and biopsy. In this situation, excision is preferred because the abnormal tissue can be examined with a microscope. This allows the physician to determine if the entire abnormal area was removed and if a more serious condition (eg, cervical cancer) is present.

Ablative therapy — Ablative therapies include cryosurgery and laser ablation. Ablative therapy may be recommended when there is less concern about cancer or about the extent of the abnormal tissue.

EXCISION — Excision is a procedure that cuts out the abnormal area on the surface of the cervix; excision can also remove abnormalities that extend inside the cervical opening. A table that compared the different techniques is provided (show table 1). Excision serves two purposes: It provides a sample of tissue to confirm the degree of an abnormality and check for cancerous or precancerous cells deep within the cervix. Excision helps to ensure that the abnormality is removed completely. If the edges of the tissue that is removed show evidence of the abnormality or precancer, further treatment may be needed.

Loop electrosurgical excision procedure (LEEP) — Excision can be done with a device that uses electrical current; this is called a LEEP procedure (loop electrosurgical excision procedure) or LLETZ (large loop excision of the transformation zone) (show table 1). A thin, wire loop is inserted through the vagina (show figure 1), where it uses an electric current to remove a cone-shaped portion of the cervix (show figure 2). This can also be performed with a laser knife, which uses high intensity energy from a light beam.

Excision can be done in the office or operating room after the cervix is injected with local anesthesia to prevent pain. The woman may feel a dull ache or cramp during the procedure. A brown paste is applied after the treatment to prevent bleeding; this often causes a dark vaginal discharge (similar to coffee grounds). Most women are able to return to work or school after the procedure.

Cervical cone biopsy (conization) — Excision can also be done with a scalpel instead of a loop; this is called a cervical conization or cone biopsy (show figure 3). Conization is usually done in an operating room after the patient has received general anesthesia (medicine given to induce sleep) or regional anesthesia (eg, epidural or spinal) (show table 1).

Following LEEP or conization, most women have mild to moderate vaginal bleeding and discharge for one to two weeks. The bleeding should not be heavy (eg, should not soak a pad in less than one hour). Care after excision is described below (see "Post-procedure care" below).

Complications — As with any surgical procedure, complications can occur during excision. These include: Bleeding during the procedure — Bleeding is rarely serious, and can usually be managed with suturing or by applying cauterizing material (a liquid or treatment that helps the blood to clot) to the cervix. Perforation of the uterus — This is an uncommon complication, and is more likely to occur in women who are postmenopausal or whose uterus is tipped forward. If the uterus is perforated it usually heals without any need for treatment. Infrequently, laparoscopy or laparotomy are required to see and repair injuries to internal organs. Bleeding after the procedure — Although light bleeding or spotting is normal, some women have heavy bleeding several days or weeks after the procedure. This can usually be treated in the office, but occasionally a procedure in an operating room is necessary. Infection — Infections occur rarely after cone biopsy, either on the cervix itself or elsewhere in the reproductive tract. Most infections can be treated with oral antibiotic therapy. Late complications — See "Pregnancy after treatment" below.

ABLATIVE TREATMENTS — Ablative treatment destroy, rather then cut away, abnormal cervical tissue.

Cryosurgery — Cryosurgery involves applying liquid nitrogen or carbon dioxide to the cervix. This causes the cervical tissue to freeze, which destroys the abnormal cells. Cryosurgery can be done in the office, similar to a pelvic examination, without any anesthesia. It may cause mild cramping or discomfort.

Cryosurgery is not recommended in certain situations, such as when the extent and type of cervical abnormality are not clear based upon colposcopy and/or biopsy. Excisional therapy is preferred in these cases.

Most women have watery vaginal discharge for one week after cryosurgery. Care after cryosurgery is described below (see "Post-procedure care" below).

Laser ablation — Laser ablation uses high intensity energy from a light beam to destroy abnormal areas of the cervix. The laser is directed to the abnormal area of the cervix through the vagina. This is usually performed in an operating room after the woman has received general anesthesia (medicine given to induce sleep) or regional anesthesia (eg, epidural or spinal). Laser treatment requires special training and equipment.

A disadvantage of laser ablation is that it destroys the abnormal tissue, similar to cryosurgery. Laser ablation is not recommended in certain situations, such as when the extent and type of cervical abnormality are not clear based upon colposcopy and/or biopsy.

Most women have vaginal discharge for one to two weeks after laser treatment. Care after laser treatment is described below (see "Post-procedure care" below).

POST-PROCEDURE CARE — All women should ask about their ability to drive home from the procedure and when they can resume normal daily activities. Following treatment, most providers recommend avoiding sexual intercourse, not placing anything in the vagina (eg, douches, tampons), and not taking a bath or swim for a few weeks (showers are fine); other physicians may recommend a shorter period of "pelvic rest." This should be discussed in detail with the physician.

In general, a woman should call her provider if she has bleeding that is heavier than a normal menstrual period (defined as soaking a pad in less than one hour, especially if there are clots), severe or worsening pain, fever over 101º F (38.4º C), or a foul-smelling vaginal discharge.

Treatment efficacy — The treatments described above cure most women with abnormal cervical cells. Women that are not cured after a first treatment may have persistence, recurrence, or progression of the abnormality, especially if a high risk type of HPV (types 16 and 18) is present. Additional treatment is sometimes needed in this case. For this reason, lifelong follow up with cervical cytology smears (Pap smear or ThinPrep) is important.

Follow up appointments — Typically, a woman is seen for a follow up examination several weeks after treatment to make sure the cervix is healing. A Pap smear (with or without colposcopy) is recommended approximately every six months. Colposcopy is recommended if atypical squamous cells or other abnormalities are found and HPV testing is positive. The time interval between subsequent tests will depend upon the results of the initial testing after treatment and the woman's age. Follow up is best discussed with a woman's individual provider since it may vary significantly from one woman to another.

Need for further treatment — Some women will require additional treatments to ensure that all abnormal areas are removed. This is especially true if excision was done and microscopic analysis showed a larger abnormality than was expected. The decision to have additional treatment is individualized, based upon the type of abnormality seen, the woman's risk of cervical cancer, and whether or not childbearing is completed. (See "Patient information: Treatment of early stage cervical cancer").

PREGNANCY AFTER TREATMENT — Many women are concerned about the risks of infertility and preterm labor after being treated for an abnormal Pap smear. The risk of these complications depends upon a number of factors, including the type and number of treatment(s) performed (ablation versus excision) and the time between the treatment and the pregnancy. In addition, other factors, such as underlying medical conditions and a woman's age, can increase a woman's risk of these conditions.

Most women are advised to wait six to 12 months after conization before attempting to become pregnant to allow the tissue to heal fully. In general, the data suggest that excisional procedures slightly increase the risk of preterm delivery, but ablative procedures do not. The risk of infertility related to treatment is probably very small. More data are needed to define these risks better. (See "Patient information: Preterm labor", section on cervical length)".

WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine

(www.nlm.nih.gov/medlineplus/healthtopics.html)
National Cancer Institute

(www.nci.nih.gov)
American Society for Colposcopy and Cervical Pathology

(www.asccp.org)
American Cancer Society

(www.cancer.org, search for HPV)
National HPV and Cervical Cancer Public Education Campaign

Telephone: 1-866-280-6605
(www.cervicalcancercampaign.org)
Center for Disease Control and Prevention

(www.cdc.gov/)
American Social Health Association

(http://www.ashastd.org/)

[1-5]

Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Martin-Hirsch, PL, Paraskevaidis, E, Kitchener, H. Surgery for cervical intraepithelial neoplasia. Cochrane Database Syst Rev 2000; :CD001318.
2. Matseoane, S, Williams, SB, Navarro, C, et al. Diagnostic value of conization of the uterine cervix in the management of cervical neoplasia: a review of 756 consecutive patients. Gynecol Oncol 1992; 47:287.
3. Gok, M, Coupe, VM, Berkhof, J, et al. HPV16 and increased risk of recurrence after treatment for CIN. Gynecol Oncol 2007; 104:273.
4. Kalliala, I, Anttila, A, Pukkala, E, Nieminen, P. Risk of cervical and other cancers after treatment of cervical intraepithelial neoplasia: retrospective cohort study. BMJ 2005; 331:1183.
5. Kyrgiou, M, Koliopoulos, G, Martin-Hirsch, P, et al. Obstetric outcomes after conservative treatment for intraepithelial or early invasive cervical lesions: systematic review and meta-analysis. Lancet 2006; 367:489.

Chronic pelvic pain in women

Treatment of abnormal Pap smears

Screening for cervical cancer

INTRODUCTION — The Pap smear is a common test used to screen women for cervical precancer or cancer. However, most abnormal Pap smears are not due to cancer, but rather caused by infection or low estrogen levels.

This topic reviews the anatomy of the cervix, factors that increase a woman's risk of having cervical precancer or cancer, tests to detect cervical abnormalities, and a description of both normal and abnormal Pap smear results. A separate topic is available that discusses treatment of abnormal Pap smears. (See "Patient information: Treatment of abnormal Pap smears").

ANATOMY OF THE CERVIX — The cervix is located at the lower end of the uterus (show figure 1). The surface of the cervix includes several layers of cells. Squamous cells make up the outer layer of the cervix and vagina.

The cervix also includes glandular (also called columnar) cells, which line the opening in the cervix. The region where the two cell types meet is called the "transformation" zone (show picture 1). The transformation zone is the region most likely to contain abnormal cells.

If more than one third of the layers contain abnormal cells, this is called high grade squamous intraepithelial lesion (HSIL or HGSIL) (show figure 2).

What is a Pap smear? — A Pap smear is a method of examining cells from the cervix. The traditional Pap smear (named after Dr. Papanicolaou) involved smearing the cervical cells onto a glass slide. More recently, liquid-based tests (eg, ThinPrep, SurePath) have become available; these tests place the sample of cervical cells into a vial containing a liquid preservative. In both types of test, the cells are viewed with a microscope to detect abnormalities.

Cervical cells may appear abnormal for a variety of reasons. For example, a woman may have low estrogen levels or a cervical infection, or she may have a precancerous area or even cervical cancer. If the Pap smear is abnormal, further testing is needed to determine what the abnormality is and if treatment is needed.

Who should have a Pap smear? — The first Pap smear should be done by age 21 years. For most women, a Pap smear is recommended every one to three years. For women who have a past history of abnormal Pap smears or who have risk factors for cervical cancer, testing is recommended once per year (see "Risk factors for cervical cancer" below).

Women who are older than 30 years who have no risk factors, a negative Pap smear three years in a row, and a negative HPV test may choose to have a Pap smear and HPV testing every three years rather than every year (see "HPV testing" below). Most experts feel that women who are at low risk for cervical cancer (eg, no past history of an abnormal Pap) can discontinue Pap smears by age 65 to 70 years.

How are Pap smears obtained? — Pap smears are performed during a pelvic examination. To perform the test, a healthcare provider uses an instrument (speculum) to view the cervix, which is located at the lower end of the uterus (show figure 1). The provider sweeps the surface of the cervix and inner cervix (called the endocervical canal) with a soft brush or small spatula to collect cervical cells. This is not painful.

Pap smear accuracy — Most Pap smears can accurately identify women with abnormal cervical cells. However, the test is not perfect, and it misses between 5 and 25 percent of women with abnormalities. These women are said to have a false negative result. There are several important points to consider when discussing false negative results: Many false negative results are due to difficulty in collecting a sufficient number of cervical cells, not errors in reading the smear. It may be difficult to collect cervical cells if the cervix is hard to find during a pelvic examination, if the abnormal area is very small or high up inside the cervix, if only a few cervical cells are obtained, if the specimen dries too quickly, if the patient douches or has sexual intercourse before the examination, or if the woman is bleeding or has an infection at the time of the Pap smear. If a woman has a normal result three years in a row, then it is unlikely that an abnormality has been missed. The frequency of screening for cervical cancer can then be spread out (see "Who should have a Pap smear?" above). If a new lesion develops in a woman who is only tested every three years, it will be found before it becomes serious because it takes years for a new abnormality to develop into a high-grade precancer or cervical cancer. It usually takes many years for precancerous cervical cells to progress to cancer, and progression to cancer does not always occur.

RISK FACTORS FOR CERVICAL CANCER — The most important risk factor for cervical cancer is infection with the human papillomavirus (HPV). Other factors that increase the risk of cervical cancer include sexual intercourse, use of tobacco (eg, cigarettes), use of birth control pills, and a weakened immune system (eg, due to HIV infection or certain medications) (show table 1).

Human papillomavirus — Infection of the cervix with certain types of human papillomavirus (HPV) is the most significant risk factor for cervical abnormalities and cancer. Over 100 different types of HPV have been identified, however not all types infect the cervix or cause cancer. Researchers have labeled the HPV types as being high or low risk for causing cervical cancer. HPV types 6 and 11 can cause warts and are low-risk types because they rarely cause cervical cancer; types 16 and 18 are considered high-risk types because they may cause cervical cancer in some women. (See "Patient information: Condyloma (genital warts) in women").

HPV is spread by direct skin-to-skin contact, including sexual intercourse, oral sex, anal sex, or any other contact involving the genital area (eg, hand to genital contact). It is not possible to become infected with HPV by touching an object, such as a toilet seat.

Most persons who are infected with HPV have no signs or symptoms. Most HPV infections are temporary and resolve within two years. When the virus persists (in 10 to 20 percent of cases), there is a higher likelihood of developing cervical cell abnormalities and cancer. However, it usually takes several years for HPV infection to cause cervical cancer (see "HPV testing" below).

Sexual history — Cervical cancer is rare in women who have never had sexual intercourse. Cervical cancer is more common in women who have had more than one sexual partner or whose partners have more than one sexual partner. Other risk factors include: HIV infection, sexual intercourse before age 17, or a history of sexually transmitted diseases (eg, genital herpes or Chlamydia).

Tobacco use — Smoking cigarettes increases the risk of cervical cancer and precancer by up to seven times that of women who do not smoke. This is believed to occur because cancer-causing products from tobacco are secreted into the cervical mucous. Stopping smoking can decrease this risk. (See "Patient information: Smoking cessation").

Birth control with estrogen — Woman who use a birth control method that contain estrogen (eg, pills, patch) have a slightly higher risk of cervical precancers and cancers compared to women who do not take them (show table 1). The risk of cervical cancer related to birth control is small, and is related to infection with HPV. Thus, women who take a birth control with estrogen but are not infected with HPV have no increased risk of cervical cancer or precancer.

The reason that oral contraceptives increase the risk of cervical cancer is not clear. Higher levels of estrogen may causes changes in the cervix that increase the growth of cells that develop as a result of the HPV infection.

However, birth control with estrogen has a number of benefits, including a reduced risk of ovarian and uterine cancer and decreased pain and bleeding with menstrual periods. Women should discuss all the risks and benefits of this type of birth control with a healthcare provider. (See "Patient information: Hormonal methods of birth control").

Weakened immune system — Normally, the immune system works to protect the body from illness and infection, including the infection caused by human papillomavirus. Women with a weakened immune system have a significantly increased risk of cancers and precancers of the cervix.

A number of factors can weaken the immune system, including HIV infection, prolonged use of glucocorticoids (eg, prednisone), and use of medications to prevent rejection after organ transplantation.

PAP SMEAR RESULTS — The information reported in a Pap smear is described in table 2 (show table 2A-B). Pap smear results may be reported as:

Negative — Pap smears that have no abnormal, precancerous, or cancerous cells are labeled as "Negative for intraepithelial lesion or malignancy".

Smears that are negative can show other conditions, such as a vaginal infection (Trichomoniasis, yeast, herpes, or bacterial vaginosis) or cellular changes related to vaginal dryness, radiation therapy, or an intrauterine device (IUD) string. In some situations, further testing and/or treatment are needed.

Abnormal results — A number of medical terms are used to describe abnormalities of the cervix, including dysplasia, squamous intraepithelial lesion, and intraepithelial neoplasia. These terms all mean that the abnormality is confined to the surface or glandular lining of the cervix.

Follow up testing — Further testing is often needed after an abnormal Pap smear. The most common tests include HPV testing and colposcopy.

HPV testing — HPV testing is recommended only in particular circumstances: If the Pap smear shows a specific abnormality (for example, atypical squamous cells of uncertain significance, or ASC-US), HPV testing is then performed. This is called reflex testing.

Testing every woman for HPV is not recommended because of the risk of false positive results (when the HPV test was falsely positive and the Pap smear was negative). It is likely that many women develop HPV infections that resolve spontaneously. Having a false positive result would lead to unnecessary follow-up testing and anxiety for many women.

Colposcopy — Colposcopy is an office procedure that allows a clinician to closely examine the cervix. It is commonly performed after an abnormal Pap smear. Colposcopy is performed similar to a pelvic examination, while the woman lies on an exam table. A speculum is used to view the cervix, and the viewing device (called a colposcope) remains outside the woman's body (show picture 2).

The colposcope magnifies the appearance of the cervix 10 times. This allows the clinician to better see the location and size of any abnormalities, and also to see any changes in the capillaries (small blood vessels) on the surface of the cervix. Capillary changes are not detected by cervical cytology or HPV tests, but are important signs of the severity of cervical abnormalities.

Using the colposcope, a small piece of the abnormal area can be removed (biopsied). Anesthesia (numbing medicine) is not needed because the biopsy causes only mild discomfort or cramping. The biopsy is then examined with a microscope by a physician (called a pathologist). The results of the biopsy are usually available within one to two weeks.

Some women also need to have a biopsy of the inner cervix during colposcopy; this is called endocervical curettage. Endocervix refers to the inner cervix and curettage means scraping.

ATYPICAL SQUAMOUS CELLS (ASC) — A Pap smear may be read as atypical when cervical cells are not completely normal but are not thought to be precancerous. Further testing of ASC is suggested because some women (5 to 17 percent) have a precancerous lesion that is seen when colposcopy is performed. ASC is subdivided into ASC-US and ASC-H; ASC-H is more likely than ASC-US to be caused by a precancerous change.

ASC-US — There are three options for follow up of a single ASC-US result: Perform HPV testing. This is the preferred follow up for ASC-US. HPV testing can often be done at the same time as the Pap smear. This is convenient because a woman does not have to return for a second visit (see "HPV testing" above).

Women who test positive for high-risk HPV types are referred for colposcopy because they are at greater risk of having a precancerous lesion.

Women who test negative for HPV are not likely to have cervical precancer. These women should have a repeat Pap smear in one year. In most cases, the ASC-US resolves on its own. Repeat the Pap smear in four to six months. If this Pap is normal, it is repeated every four to six months until there have been two normal tests in a row. If the woman has two ASC-US results, she should have colposcopy.

For postmenopausal women, use of an estrogen treatment in the vagina for one month may be recommended after one ASC-US result; low estrogen levels in the vaginal and cervical tissues can cause mild cellular abnormalities that often revert to normal after estrogen treatment. Colposcopy should be performed if the woman has a second ASC-US result after use of estrogen therapy. Have colposcopy. This approach is preferred for women who are HIV positive or who have a weakened immune system because of the higher risk of a precancerous lesion (see "Colposcopy" above).

ASC-H — This finding requires further testing with colposcopy (see "Colposcopy" above).

LOW-GRADE SQUAMOUS LESION (LSIL) — These are mild cellular changes. Further testing is almost always recommended for women with LSIL because 15 percent of women with LSIL have a precancerous lesion that was not detected by the Pap smear.

A small number of women with low-grade changes will develop cancer over a period of several years if no treatment is performed. A large percentage (50 to 90 percent) of women with low-grade changes do not require treatment because the abnormality resolves on its own.

Low-grade abnormalities may be described with other names, including low-grade squamous intraepithelial lesions (LSIL), cervical intraepithelial neoplasia, grade 1 (CIN 1), and mild dysplasia.

Follow up of LSIL — Colposcopy is recommended for women with low-grade lesions (LSIL) (see "Colposcopy" above). Determining the size and location of the lesion with colposcopy can help to decide whether to treat the lesion or follow it over time. Large lesions are less likely to heal without treatment. Observing the extent and severity of the lesion with colposcopy is useful for establishing a baseline in women who are not treated.

However, LSIL in postmenopausal or adolescent women may be approached differently. A repeat Pap smear or HPV test may be recommended for adolescents; if the HPV is positive or the Pap smear continues to be abnormal, the adolescent is usually referred for colposcopy. Postmenopausal women may be treated with a course of estrogen cream, as described above (see "Atypical squamous cells (ASC)" above).

Treatment of LSIL — There are three options for management of LSIL: Close follow-up with HPV testing after 12 months or repeat Pap smear at six and 12 months. Colposcopy is performed if abnormalities persist or worsen (see "Follow up testing" abovesee "Follow up testing" above). HPV testing is preferred because it is as effective as Pap smear but requires fewer visits and less need for colposcopy. Treatment to remove or destroy the abnormal cells (See "Patient information: Treatment of abnormal Pap smears"). Repeat colposcopy and Pap smear at 12 months.

Since many of these lesions will heal without treatment, some women prefer to delay treatment and have close monitoring. Treatment is the best option if LSIL persists, if the woman would have difficulty remembering to follow-up every six months, if the lesion is large (large lesions usually persist), if the lesion extends into the inner cervix (where it is difficult to see), or if the patient prefers treatment.

HIGH-GRADE SQUAMOUS LESION (HSIL) — These are moderate to severe changes in the cells of the cervix that may be precancerous (show picture 1). Approximately 20 percent of women will develop cervical cancer over a period of several years if no treatment is given.

A number of terms are used to describe high grade lesions, including CIN 2 and 3, moderate and severe dysplasia, and carcinoma in situ (CIS).

Follow up of HSIL — All women with high-grade lesions (HSIL) should have a colposcopy and biopsy. If colposcopy does not detect a high grade abnormality, close follow-up, further testing, and/or treatment may be recommended.

Treatment of HSIL — Women with high grade abnormalities should be treated because approximately 20 percent of untreated abnormalities will develop into invasive cancer. The most common treatment involves removal (excision) of the abnormal area of the cervix. (See "Patient information: Treatment of abnormal Pap smears").

Adolescent patients may be able to delay treatment of HSIL because, in this age group, there is a good chance that the abnormal area will heal without treatment. Close follow up is required, including colposcopy and Pap smear every four to six months. To delay treatment, the provider must be able to see the entire cervix during colposcopy and a test of the inner cervix (called endocervical curettage) must be negative.

Likewise, for pregnant women with HSIL, treatment is often delayed until after delivery. Colposcopy and Pap smear are generally performed several times during the pregnancy.

SQUAMOUS CELL CARCINOMA — Squamous cell carcinoma is the medical term for cervical cancer. Women with this result require a biopsy, which is usually performed with colposcopy. If biopsy confirms that cancerous cells are present, treatment is strongly recommended. The diagnosis and treatment of early stage cervical cancer is discussed in a separate topic review. (See "Patient information: Treatment of early stage cervical cancer").

GLANDULAR CELL ABNORMALITIES — Glandular cells develop from the inside the cervix (called the endocervical canal). Glandular cells can also come from the endometrium (lining of the uterus), the fallopian tube, or the ovary. Women with abnormal glandular cells need to have further testing to determine the source of the abnormality, if cancer or precancer is present, and to determine if treatment is needed.

Follow up testing — All women with atypical glandular cells (AGC) require further testing (colposcopy, biopsy, endometrial biopsy). This is because 10 to 40 percent of women with atypical glandular cells have precancerous or cancerous cells when evaluated by colposcopy and biopsy.

Treatment — Treatment of AGC depends upon the underlying abnormality and may involve monitoring, removal of a large part of the inner cervix, or less commonly, hysterectomy. (See "Patient information: Treatment of abnormal Pap smears").

PREVENTING CERVICAL CANCER

HPV vaccine — A vaccine (Gardasil®) is now available to help prevent infection with some types of HPV (types 6, 11, 16, and 18). Approximately 70 percent of cervical cancers result from infection with HPV 16 and 18, and approximately 90 percent of cases of genital warts result from infection with HPV 6 and 11. The vaccine was proven to be safe and effective in several large clinical trials [1,2].

The vaccine is currently recommended for all females who are between ages 9 and 26 years. Decisions about the age at which to start HPV immunization have been guided by the age at which the greatest number of women is infected with HPV and estimates regarding how long the vaccine continues to prevent infection. While it is not known exactly how long the vaccine protects against HPV infection, clinical trials prove protection for at least four years [3]. Further study is underway to determine if a booster shot is needed after this time.

The vaccine has not been studied in women over 26 years old and thus its effectiveness is uncertain. Women over this age are more likely to have been exposed to the four types of HPV in the vaccine (6, 11, 16, and 18); the vaccine does not protect against HPV infection if the woman has previously been exposed.

The vaccine is given by injection and requires three doses; the first injection is followed by a second and third dose two and six months later.

It is not known if vaccination of men could help to reduce the incidence of cervical cancer in women. Studies are currently underway to address this question. The vaccine is not currently recommended during pregnancy.

Sexual contact — Avoiding sex or sexual contact is not a practical way to prevent infection with HPV. Condoms provide partial protection, but not complete protection because they do not cover all areas of the genitals. Having a limited number of sexual partners may reduce the risk of HPV infection.

Smoking cessation — Women who smoke cigarettes are at increased risk of developing cervical cancer [4]. Cigarette smoking and HPV infection increase the risk of developing high-grade squamous lesions. The risk of cervical cancer is increased two- to four-fold among cigarette smokers compared to nonsmokers.

Women who smoke and have an abnormal Pap smear can reduce their risk of cervical cancer by quitting smoking. (See "Patient information: Smoking cessation").

WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine

(www.nlm.nih.gov/medlineplus/healthtopics.html)
National Cancer Institute

(www.nci.nih.gov)
American Society of Cytopathology

(www.cytopathology.org)
American Society for Colposcopy and Cervical Pathology

(www.asccp.org)
American Cancer Society

(www.cancer.org, search for HPV)
National HPV and Cervical Cancer Public Education Campaign

Telephone: 1-866-280-6605
(www.cervicalcancercampaign.org)
National Institute of Allergy and Infectious Diseases

(www.niaid.nih.gov/factsheets/stdhpv.htm)
Center for Disease Control and Prevention

(www.cdc.gov/)
American Social Health Association

(http://www.ashastd.org/)

[1-9]

Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Koutsky, LA, Ault, KA, Wheeler, CM, et al. A controlled trial of a human papillomavirus type 16 vaccine. N Engl J Med 2002; 347:1645.
2. Harper, DM, Franco, EL, Wheeler, C, et al. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial. Lancet 2004; 364:1757.
3. Harper, DM, Franco, EL, Wheeler, CM, et al. Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial. Lancet 2006; 367:1247.
4. Carcinoma of the cervix and tobacco smoking: Collaborative reanalysis of individual data on 13,541 women with carcinoma of the cervix and 23,017 women without carcinoma of the cervix from 23 epidemiological studies. Int J Cancer 2006; 118:1481.
5. Solomon, D, Davey, D, Kurman, R, et al. The 2001 bethesda system: terminology for reporting results of cervical cytology. JAMA 2002; 287:2114.
6. Wright, TC Jr, Cox, JT, Massad, LS, et al. 2001 consensus guidelines for the management of women with cervical cytological abnormalities. JAMA 2002; 287:2120.
7. Human PAP illomavirus testing for triage of women with cytologic evidence of low-grade squamous intraepithelial lesions: baseline data from a randomized trial. The Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesions Triage Study (ALTS) Group. J Natl Cancer Inst 2000; 92:397.
8. ACOG Practice Bulletin #66: Management of Abnormal Cervical Cytology and Histology. Obstet Gynecol 2005; 106:645.
9. ACOG Committee Opinion No. 344: Human papillomavirus vaccination. Obstet Gynecol 2006; 108:699.

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Monday, October 15, 2007