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Adam S. Levine, M.D. recently finished his fellowship in reproductive endocrinology and infertility within the department of gynecology and obstetrics at the Johns Hopkins University School of Medicine. His areas of expertise include reproductive endocrinology, infertility, assisted reproductive technology, reproductive surgery, pediatric and adolescent gynecology, and menopause.

 

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PAP smears & cancer

Q:    My 17-year-old daughter was told she had cell abnormalities after a recent Pap smear. She was sent a follow-up letter, which mentioned dysplasia and condylomiosis, and advised to schedule another doctor appointment to check for atypia. What is atypia? And what is dysplasia and condylomiosis? Should we be concerned?	A:   Pap tests (also called Pap smears) are screening tests used to detect cervical abnormalities (cancer or pre-cancerous conditions). Pap tests are recommended on an annual basis for all sexually active women. The cervix is the entryway between the uterus and the vagina. The portion of the cervix in the vagina is the area that is most likely to develop cervical cancer.    During a Pap test, samples are taken from inside the cervix with a brush or swab, and from the outside of the cervix with a spatula. These samples are placed on a glass slide and are examined under a microscope. There are several different methods used to evaluate these slides.    Generally the slides will either be adequate or inadequate for evaluation. Slides that are inadequate may have too few cells to examine or have some kind of processing error. Pap tests may be normal or abnormal. If a test is normal, it should probably be repeated in 12 months. The development of cervical cancer generally follows a set path that develops over many years.    The first step in the development of cancerous cells is referred to as ASCUS; or atypical squamous cells of undetermined significance. ASCUS is a minor abnormality that is likely to become normal over time without treatment. Many physicians will suggest a repeat Pap test three to six months after the first. If the second test is abnormal, a colposcopy will be suggested. A colposcopy is a test where a gynecologist can examine the cervix in the office under magnification, and biopsy areas that appear abnormal.    The second, third and fourth steps of abnormality are referred to as CIN I, II and III; cervical intraepithelial neoplasia I, II and III (this is dysplasia). CIN reflects progressive stages of abnormality. CIN III may also be called carcinoma in situ that means that there is a microscopic area that looks like cancer. In any of these cases, a colposcopy is performed to evaluate the extent of the abnormality and determine which kind of treatment is best.    Conditions such as condyloma are caused by specific types of sexually transmitted viruses. Most sexually active women have at least one type of this virus. Unfortunately, there is no good way to treat the virus, and in many cases it may cause the cells on the Pap test to look abnormal. A few types of these viruses may predispose a woman to develop dysplasia. Women with abnormal Pap tests will benefit from a discussion with their gynecologist.
Q:   Are there any specific tests for detecting ovarian cancer? If so, at what age should women be tested?	A:   Unlike PAP tests for detecting cervical cancer, and mammograms and self-breast examination for detecting breast cancer, there are no specific screening tests for detecting ovarian cancer in women. Usually a woman has a pelvic or abdominal complaint, such as a significant increase in waist size and an unusual finding during her yearly pelvic examination. Her gynecologist may order several different types of tests to try to differentiate between benign and malignant (cancerous) conditions.    There are two different types of tests. The first type of test is a blood test. The most common is called a Ca-125. The Ca-125 level is elevated in ovarian cancer. However, the Ca-125 may also be elevated in benign conditions such as endometriosis. The second type of test is an imaging test using ultrasound, CAT scans or MRI. In some cases, ultrasound is used to detect ovarian blood flow. This may also help differentiate between benign and malignant conditions.    Unfortunately, none of the available tests is good enough to use as a screening test for the general public. The best test remains a yearly gynecologic evaluation. Notably, ovarian cancer is more common in older women.
Q:   How often can cervical cryotherapy be performed? Are better results obtained from laser (LEAP) surgery?	A:   Cryotherapy and laser surgery are two methods used to correct abnormalities detected on a Pap test. Cryotherapy is usually done in the office. Women may have mild cramping during the procedure that may be treated with ibuprofen or Tylenol. Basically, the abnormal area of the cervix is frozen. The freezing process destroys several layers of cells, removing the abnormal ones in the process. Cryotherapy is 95 percent effective. In the 5 percent of cases where it does not work, or in cases where the cervical abnormality returns, it may be used again with a repeated 95 percent efficacy. There are no disadvantages to using cryotherapy on several occasions. The major benefit of cryotherapy is that very little of the cervix is removed, and consequently, should not have an impact on future pregnancy. The disadvantage of cryotherapy is that a woman may have a vaginal discharge for several days following the procedure.    Laser surgery is one of several methods where a larger portion of the cervix is either removed or vaporized. These procedures are also referred to as LEEPS, LOOPS, etc. They may done in the office or operating room. Women may have mild to moderate cramping during the procedure and for a short time afterwards. The procedure is as effective as cryotherapy, but a significantly larger area of the cervix is removed which may impact future pregnancy. Depending on the amount of the cervix that is removed, the procedure may be repeated if necessary. There will also be a vaginal discharge for several days following these procedures.    Before undergoing any kind of treatment, a woman should discuss the different types of therapy with her gynecologist.
Q:   Is it necessary for a woman who has had a hysterectomy to get annual pap smears?	A:   Yes. An annual PAP smear should be obtained from the area that used to contain the cervix. Potentially, a small portion of the cervix may be left behind following a hysterectomy. In extremely rare circumstances, cervical cancer may develop in these areas. In many cases, after consultation with her gynecologist, a woman may elect to have less frequent PAP smears (every one to three years) after several completely normal annual PAP smears.
Q:   I was informed by my gynecologist that the result of my pap smear test was fine, but that there were signs of inflammation. He recommended that I should be re-tested in 3 months. Does this mean that the pap smear was 'abnormal?' Does this indicate a pre-cancerous condition? What classification is this on the 'Bethesda system?'	A:   Pap Tests (also called Pap Smears) are screening tests used to detect cervical abnormalities (cancer or pre-cancerous conditions), and are generally recommended on an annual basis in all sexually active women. There are several different schemes used to interpret Pap tests; the Bethesda System is one. In the Bethesda System, as in most of the other schemes, inflammatory changes alone are interpreted as a normal Pap test. These changes may occur as a result of a sub-clinical (not symptomatic) or transitory vaginal infection with associated inflammation. Inflammatory changes are not pre-cancerous conditions. Further, women with inflammation noted on Pap test interpretation do not necessarily need to be treated. The Pap test may be repeated in three to 12 months, depending on a woman's individual circumstances, such as prior history of abnormal Pap tests, vaginal infections, other medical problems and age.
Q:   A recent ultrasound revealed calcifications on my ovaries. What does this mean? Is this a pre-cancerous condition?	A:   In many cases, ultrasound examinations are used as an adjunct to a pelvic exam. Ultrasound examinations use reflected sound waves to create an image of structures beneath the skin. They are best used to determine if something that has been detected on routine examination is solid or filled with fluid. They are also frequently used to measure the actual size of what has been felt by examination. Pelvic masses may be felt during routine pelvic examinations. Commonly found in reproductive age women, these masses are usually benign ovarian cysts that form every month as part of the normal ovulatory process (maturation and release of an egg from the ovary). Pelvic masses in pre-menstrual girls or in post-menopausal women are unusual, and may be related to other processes such as benign or malignant tumors.    Calcifications may be noted during ultrasound examination, and they are frequently benign. In unusual circumstances, they may be associated with malignancy. However, for the most part, ovarian calcifications detected by pelvic ultrasound are not pre-cancerous conditions.
Q:   Can chemotherapy cause premature menopause?	A:   Premature menopause is technically defined as menopause occurring before the age of 40. The basic answer to this question is yes, chemotherapy can cause premature menopause. However, there are a large number of chemotherapeutic agents as well as many different chemotherapy protocols. Some agents and protocols are more likely to result in premature menopause. A woman who is either undergoing chemotherapy or considering it should discuss premature menopause with her health care provider or gynecologist. In most cases, women having premature menopause may be treated with routine kinds of hormone replacement therapy.
Q:   I had genital warts that turned into Bowen's Disease. Is this a form of skin cancer?	A:   Vaginal intraepithelial neoplasia (VIN) is a pre-cancerous change in the skin of the vulva. Genital warts (technically termed condyloma acuminata) and Bowen's Disease are both types of VIN. The skin of the vulva is similar to skin on the rest of the body. It can develop cancer, but pre-cancerous lesions are far more common. Vulvar cancer is generally thought of as a progression from a pre-cancerous change over time to an invasive cancer. VIN is more common in women between the ages of 40 and 50, and may be suspected if there is a persistent irritation or rash. There are several methods of adequately treating VIN including topical chemotherapy, surgical removal and the use of a laser to vaporize the abnormal tissue. Women with VIN should seek a gynecologist's care.
Q:   I've had a complete hysterectomy, including cervix removal. Do I still need to have Pap smears?	A:   Yes. I recommend that women who have had a complete hysterectomy (surgical removal of the uterus, cervix, ovaries and fallopian tubes) with benign pathology have a Pap smear 6 to 12 months after the initial surgery. I would repeat the Pap smear every year until three absolutely normal results are reported. I would then suggest repeat Pap smear every 2 to 3 years.    There are two reasons that I recommend Pap smears after complete hysterectomy. The first is that no matter what kind of surgery was performed, there is a small chance that a small portion of the cervix may be left in the vagina following surgery. The second reason is that the Pap smear is a good screening test for new vaginal abnormalities.
Q:   What does it mean when the doctor tells you this is the second irregular PAP smear and there is evidence of CIN1? I have been told to make an appointment for a biopsy to see if what I have is pre-cancerous. I've never had any evidence of any virus and everything has been very normal. What can I expect? Does this mean I have cancer? Is my situation curable? Is my situation terminal? What are some things I should know?	A:   Pap test is a screening test that is used to detect cervical cancer. Basically, a sample of cells from the cervix is examined under a microscope by an experienced cytologist or cytopathologist - medical personnel who specialize in examining microscopic specimens. By evaluating the structure of the cervical cells, the cytologist can determine whether the cells are completely normal or score how abnormal they appear (dysplasia). Importantly, very few women with abnormal pap tests actually have cancer.    There are many reasons why a Pap test may be abnormal. Women who have abnormal Pap tests commonly have human papilloma virus. This virus is a sexually transmitted disease that may cause cervical cells to undergo pre-cancerous changes. Cervical cancer develops over a period of several years. During that time there is an orderly, step-wise change from normal cells to cancer. The first step is referred to as ASCUS (atypical squamous cells of undetermined significance). These cells look slightly abnormal for a variety of reasons. In some cases, an infection may be noted and treated. The next step is CIN I (cervical intraepithelial neoplasia), followed by CIN II and CIN III. These cells look progressively more abnormal. CIN III is also referred to as carcinoma-in-situ (CIS); this is an early form of non-invasive cancer. Following CIN III, there is invasive cervical cancer.    There are a variety of acceptable methods for evaluating women who have abnormal pap tests. If a Pap test returns as ASCUS or CIN I (in some cases) a repeat Pap test may be done in 3 to 6 months. If the Pap test remains abnormal, then the physician will suggest a colposcopy. A colposcopy is an examination of the cervix in the office under magnification. If there is an abnormality noted, a biopsy of the abnormal area can be performed. This biopsy allows the cytopathologist to make a more accurate diagnosis. A colposcopy is usually the next step for pap tests with CIN II or CIN III.    There are also several acceptable treatments available for women with dysplasia following colposcopy. Women with ASCUS or CIN I may choose treatment or can be safely followed with pap tests every 6 months. Treatment is recommended for CIN II or CIN III. In most cases the abnormal area of the cervix can be removed by one of several methods {cryosurgery (freezing), electrocautery (removing part of the cervix with electrical current), or laser (vaporization)}. In cases where the diagnosis remains in question or is CIS, a cone biopsy may be suggested. This is where a larger area of the cervix is removed to determine exactly how large the abnormal area is.    Abnormal pap tests should be discussed with your health care provider. An abnormal Pap test is rarely a terminal condition. However, to prevent cervical cancer, it is extremely important for women with abnormal pap tests to seek follow-up and treatment.
Q:   My doctor has suggested that I cut my take of progestin from 10 to five days, since I complained of three days of light bleeding when both the progestin and estrogen are stopped for the last five days of the month. He said this would cut down on the amount of bleeding, but I am concerned after reading the warning from a Reuters story about endometrial cancer. What do you think?	A:   There are several well-accepted methods of prescribing hormone replacement therapy. Women having a uterus should be given both estrogen and a progestogen. Estrogen therapy provides many benefits (decreasing heart disease, decreasing bone loss, improving memory, decreasing wrinkles etc.), but causes the lining of the uterus (endometrium) to grow. Over time, this uncontrolled growth will increase a woman's chance of developing endometrial cancer.    Progestogens are added to the hormone replacement regimen to control endometrial growth and prevent cancer. Both the minimum amount of progestogen, and the shortest exposure to progestogen necessary to control endometrial growth, are controversial. The available data support the use of either moderate doses (5 to 10 mg/day) of progestogen for 10 to 12 days, or the use of smaller (2.5 mg/day) daily doses of progestogen.    Generally, it is possible to safely manipulate hormone replacement regimens so that women will not have bleeding or spotting. Changing to a continuous hormone replacement regimen (medication every day) should eliminate spotting or bleeding that may occur when the medication is temporarily stopped. It is important to note that although post-menopausal bleeding or spotting may result from hormonal changes (stopping hormone replacement periodically), it may also represent another potentially more serious problem (uterine polyp or malignancy). Women with post-menopausal bleeding should discuss this with their gynecologist.