Women's Health Articles - PAP Smear and Cervix/Vaginal Problems

Signs and Symptoms of Vulvovaginal Candidiasis

Frederick R. Jelovsek MD

Many reproductive age women have experienced vulvovaginal candidiasis or "yeast" infections in their lifetime. However candida species of yeast can also exist in the vagina without causing symptoms and can be found in up to 15% of asymptomatic women. Yeast symptoms of itching and burning often overlap with other conditions such as allergic or irritant vulvitis that we have written about in the past. Then what exactly are the signs and symptoms of yeast vulvovaginitis and how reliable are they to use alone, without any cultures or microscopic exams, to make a diagnosis on which to begin treatment?

A recent article, Eckert LO, et. al: Vulvovaginal candidiasis: Clinical manifestations, risk factors, management algorithm. Obstet Gynecol 1998; 92:757-65, looked at this diagnosis problem in 774 women coming to a an STD clinic, but not ones who had been specifically referred for yeast infections as have previous studies on this subject. They collected a thorough set of symptoms and physical signs along with a measurement of vaginal pH, microscopic exam of the discharge (for yeast, trichomonas and bacterial laden vaginal cells) as well as a microscopic exam of the cervical mucous to detect inflammatory (white blood) cells. They also performed vaginal secretion cultures for candida species, trichomonas, and mycoplasma and cervical cultures for gonorrhea and chlamydia

In this group of women who had positive cultures for candida albicans (remember some women have positive cultures but no symptoms) signs of vulvar swelling, cracked skin fissures, a reddened vulva or sores from scratching and a thick, curdy vaginal discharge were infrequent. When the women had their symptoms and findings categorized by whether the culture was positive or negative and whether the microscopic wet-prep was positive or negative, the frequencies in the different groups were interesting.

Symptoms and Signs by Test Results

From a women's point of view, this means that you can easily have a yeast infection without having burning and itching of the vulvovaginal area. Also though, you can't tell by the color or even presence of a discharge what kind of infection you have.

From the doctor's point of view (exam), vulvar redness is present 3/4's of the time, but not always. A thick, curdy (cottage cheese) vaginal discharge which we think is classic for candida infection, is only present about 30% of the time.

These authors also looked at whether other factors were associated with a higher incidence of positive yeast cultures. They found that recent antibiotic use, condom use, a past history of gonorrhea infection (don't ask me why) and not having had any previous pregnancies was associated with a higher incidence of positive cultures. Interestingly, they also found that there was no higher incidence of positive cultures:

• by use of oral contraceptives
• with absent lactobacillus (the normal vaginal bacteria)
• by symptoms starting in the last half of the menstrual cycle
  (luteal phase when progesterone is present)

Using all of this data, these authors offered a management strategy for doctors. A microscopic wet mount test should be performed on all women who have symptoms or who, on exam, have findings of vulvar redness or swelling or a thick curdy discharge on speculum exam. If the wet mount test is positive for yeast, treatment should be started ( this is usually how doctors do it now). If the wet mount is negative, a culture should be performed if any physical exam signs are positive but the woman has no symptoms, or, if there are no positive exam signs but a woman has multiple symptoms. If the culture is positive, treatment is begun.

For a woman to attempt self-treatment without a doctor's exam, if you have a main problem of vulvar itching and/or burning, there is about a 50% chance that a vaginal culture would be positive for yeast. You would save a doctor's visit by self-treating but if the problem does not go away or recurs within a week of finishing the over-the-counter, anti-yeast medication, you should see the doctor to be sure of the diagnosis or a least start looking for other causes of vulvar irritation.

Natural Progression of an Abnormal Pap

Frederick R. Jelovsek MD

Approximately 2-5% of Pap smears will have an abnormal result. The usual abnormal result categories are:

• ASCUS - Atypical cells of uncertain significance
• low grade squamous intraepithelial neoplasia (LGSIL) or mild dysplasia
• high grade squamous intraepithelial neoplasia (HGSIL) consistent with moderate or severe dysplasia

A recent study, Melnikow J: Natural history of cervical squamous intraepithelial lesions: A meta-analysis. Obstet Gynecol 1998;92:727-35, looked at all scientific studies in the literature since 1970 in which women with abnormal Paps were followed but not treated. They then analyzed how often the specific Pap smear improved on it's own and how often it progressed to a worse lesion:

Abnormal Pap Smear
Natural Progression and Regression

The studies analyzed took the Pap smear on entry as the true finding when in fact we know the Pap is a screening test and as such has some false negatives (could explain progression) and false positives (could explain regression).

How does HPV (human papilloma virus) affect progression of the Pap? In one study(1), The rate of CIN progression was higher with HPV (50.5%) than without HPV (35.4%). Of the CIN cases with HPV 16, 56.5% progressed, while 30.8% of the CIN cases with HPV 6 and/or 11 and 35.4% of the CIN cases without HPV progressed. In other words, HPV subtype 16 was associated with a higher progression rate but not all subtypes of HPV.

Another older study before HPV sub typing(2), looked at progression or regression of a Pap smear showing HPV.

1. Konno R, Paez C, Sato S, Yajima A, Fukao A
HPV, histologic grade and age. Risk factors for the progression of cervical intraepithelial neoplasia.
J Reprod Med 1998 Jul;43(7):561-6

2. Rome RM, Chanen W, Pagano R
The natural history of human papillomavirus (HPV) atypia of the cervix.
Aust N Z J Obstet Gynaecol 1987 Nov;27(4):287-90



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Irritant Vulvitis Often Misdiagnosed as Yeast

Frederick R. Jelovsek MD

Many women equate burning and itching of the vulva with a yeast vaginitis. Often their doctors and nurses do the same thing. Consider for a moment, that many episodes of vulvar irritation may actually be a primary vulvar dermatitis with a secondary yeast colonization. This is quite a different concept, isn't it. It means that on some occasions we need to primarily treat a contact or irritant dermatitis rather than rushing out to get the anti-yeast cream.

If that's the case, what are the irritants? In a recent article, Summers, PR: Vulvovaginal candidiasis: Investigating the dermatologic connection. Obg Management 1998 August Suppl:2- 6, the point was made that many women are sensitive to common constituents of creams used to actually treat vulvovaginitis:

• propylene glycol
• methylparaben
• butylated hydroxyanisol (BHA)
• cetyl alcohol
• sodium lauryl sulfate
• methyl benzethonium chloride
• fragrance

Lubricants, spermicides, scented sanitary products, douches, soaps, and even bubble baths have also be implicated in causing irritant vulvar dermatitis. We have had women on the message board who have been sensitive to lubricants used in condoms. Dr. Summers estimates that almost 50% of the patients seen a special vulvar clinic have a primary irritant dermatitis with or without a secondary yeast vulvovaginitis. This is consistent with one study which did skin patch allergen testing on the vulva and found almost 50% of women allergic to common chemicals in soaps and creams.

Treatment of a contact vulvitis is to protect the skin with petrolatum or solid vegetable oil and to elimininate any further contact with soaps or creams or any other chemicals. Sometimes steroid creams are needed. Be sure to look at the chemical constituents in any products you are using on the vulva or in the vagina.



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Atypical Glandular Cells of Unknown Significance (AGCUS) on Pap

Frederick R. Jelovsek MD

A call from the doctor's office about an abnormal Pap smear ranks as a bad news day in anyone's book. While the first thought is possible cancer of the cervix, there a many grades of abnormal that are not cancerous. Cancer is certainly the worst grade of an abnormal Pap; atypical squamous cells of undetermined significance (ASCUS) is the least abnormal grade. In between, is mild, moderate and severe dysplasia. All of these classifications refer to the squamous cells that line the outside of the cervix and vagina. These are the cells that are exposed to sexual intercourse and whatever bacteria, viruses and irritants that accumulate over the years.

There is one other type of abnormal cervical cells, glandular cells on the inside of the cervical canal. The extreme abnormality of these is adenocarcinoma of the cervix rather than the more usual squamous cell carcinoma of the cervix. The mildest abnormality of these glandular cells is atypical glandular cells of undetermined significance (AGCUS or AGCUS). This is an infrequent category of abnormal Pap but it is more worrisome than squamous cell atypia (ASCUS).

In a recent article, Cox JT: AGUS Pap smears - A follow-up strategy. OBG Management 1998;July:74-87, a diagnostic strategy was outlined to evaluate AGUS Pap smears. It's work up is quite different than the squamous cell atypia because 20-50% of women with this Pap result have a more severe, hidden lesion that requires diagnosis lest it progress into, or already represents, an existing cancer. Doctors currently have a tendency to treat this category without the respect that it deserves, because the more commonly occurring squamous abnormality, ASCUS, is much less frequently associated with more advanced lesions. In addition, glandular lesions can progress to a cancer more rapidly than a squamous lesion. They are also more difficult to detect by colposcopy.

The evaluation process for a squamous atypia, ASCUS, is just to repeat the Pap in 3-6 months. For AGUS, Dr. Cox and the American Society of Colposcopy and Cervical Pathology, recommend an immediate colposcopy and, at that time, an endocervical curetting (scraping) to diagnose any worse changes up inside the cervical canal where you can't see with the colposcope. If there are any abnormal changes on the curetting, a conization of the cervix should be done. That can be a LEEP (loop electrical excision procedure) conization in the office or a "cold knife" conization in the outpatient surgery unit.

Women need to know that there is intense physician disagreement about the best way to work-up both ASCUS and AGUS, but also, they need to know that they are two different Pap abnormalities -- one, AGUS being much more worrisome and needing more aggressive diagnosis, than the other, ASCUS. Make sure you know which pap abnormality you have.



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Papillomavirus Testing of Abnormal Pap Smears

Frederick R. Jelovsek MD

The human papillomavirus (HPV) has been identified as the most common culprit associated with abnormal Pap smears. Some strains of HPV are apparently more virulent than others and HPV subtypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68 have been associated with severe grades of cervical dysplasia and invasive cancer of the cervix. DNA test is used to identify subtypes of HPV and up to now it has been more expensive and inconvenient to offer as routine testing. Theoretically, if all women with abnormal Pap smears could have HPV subtype testing then those associated with the more virulent strains would be the only ones requiring treatment.

Right now the rule-of-thumb in the U.S. is to follow women with ASCUS (atypical squamous changes of undetermined significance) and mild dysplasia (CIN I) with repeat Pap smears every 3-6 months. That is because most of them go away on their own as the woman's body mounts an immune response. Moderate or severe dysplasia changes are usually treated with procedures that destroy the affected cells along with normal tissue. It would be nice to know which women with ASCUS or mild dysplasia were going to get worse with time. Then they could be treated early. Also it would be nice to know which women with moderate or severe dysplasia could be followed with just repeat Pap smears rather than having to have a destructive procedure to the cervix that may affect future fertility.

With the advent of the thin Pap, there is fluid left over from the specimen that can be tested for HPV DNA without having the woman return for an additional visit and procedure to obtain a specimen -- Pap or biopsy. Thus if a Pap is abnormal, it can be immediately tested for worrisome HPV strains. A recent study looked at the practicality of this. Wright Jr. TC, et al.: Reflex human papillomavirus deoxyribonucleic testing in women with abnormal Papanicolaou smears. Am J Obstet Gynecol 1998; 178:962-6.

These authors studied 265 women with different grades of Pap smears and biopsies. They found that in patients who had ASCUS, the lowest grade of Pap abnormality, HPV DNA testing could identify 90% of those women who were likely to have a more severe lesion (high grade dysplasia) on actual biopsy. Unfortunately, with the higher grades of Pap abnormality, the testing was not sensitive or specific enough to be useful as to which women could be followed rather than biopsied.

While more studies have to be done in this area, our knowledge about abnormal Paps and HPV has advanced significantly in the last decade and if the thin Pap test becomes more widely used, we will see more studies about HPV association that will help us know in which instances to treat or not treat with greater precision.



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Yeast Vaginitis - Treat the Symptoms or Diagnose by Culture?

By Frederick R. Jelovsek, M.D.,

With symptoms of vaginal burning and a white, curdy discharge, many women have learned to self-treat with non-prescription, over-the-counter anti fungal medications. They are wrong only 25% of the time.(1) In many instances though, this treatment may permanently cure the problem. But what happens when the symptoms quickly recur or when this is the fourth time in a year to get an infection?

The answer for an accurate diagnosis to make sure the infection is due to yeast organisms (Candida albicans). For the first step, doctors usually look under the microscope at a wet prep of the discharge to identify yeast organisms. It is important for the doctor to make sure there is not a trichomonal or bacterial infection. Sometimes however, a woman can have a yeast infection but the number of organisms is too low to show up under the microscopic exam. On other occasions, the microscopic wet prep may show yeast organisms but they may be resistant to the common medications. They may also be yeast organisms other than the common Candida albicans yeast, such as non-albicans Candida species, Torulopsis glabrata or Saccharomyces cerevisiae which don't respond as well to the usual anti fungal medications.

At this point it is best to obtain a specimen of the vaginal discharge and send it for yeast culture. If it returns as Candida albicans or one of the other yeasts, this may represent a problem of resistant organisms and different therapies should be tried. If no yeast is cultured, that also is important in that it tells us to look for other uncommon causes of vaginitis such as physiologic discharge, allergic vaginitis, desquamative vaginitis, atrophic vaginitis or sometimes a vulvar irritation that is primary rather than being caused by a vaginal discharge.

In summary, any recurrent vaginitis (four or more in a year) should be cultured if it is thought to be a yeast vaginitis or if it is not clear from the microscopic wet prep what the organism is.

1. Ferris DG, Dedle C, Litaker MS. Women's use of over-the- counter anti fungal pharmaceutical products for gynecologic symptoms. J Fam Pract 1996;42:595-600.

PAP Smear Diagnosis of Endometrial Cancer

By Frederick R. Jelovsek, M.D.,

Pap smears are used to diagnose cervical cancer. The cervix is the lower part of the uterus, the mouth of the womb. The Pap test is not very accurate for diagnosing endometrial cancer which is from up in the menstrual lining of the uterus. Only 50% of the time that endometrial cancer is present are the Pap smears positive for (glandular) cancer cells. This is not a high enough percentage to be used as the primary diagnostic test; endometrial biopsy is usually the diagnostic procedure of choice although D&C and hysteroscopy are also used.

Sometimes a Pap smear is suggestive of endometrial cancer rather than cervical cancer and we need to know what it means. G.L. Eddy and others recently looked at how Pap smears were read within 1 year of the diagnosis of endometrial cancer, Eddy GL, Wojtowycz MA, Piraino PS, Mazur MT. Papanicolaou smears by the Bethesda system in endometrial malignancy: utility and prognostic importance. Obstet Gynecol 1997 Dec;90(6):999-1003. They found that almost half the patients had a abnormal Pap. More importantly, if the Pap smear was suspicious for endometrial cancer, the cancer was a more severe type. In other words the cancer had invaded further or was of a more "malignant" type than in women who did not have a positive Pap.

This study means that if a woman has a Pap smear suspicious for endometrial cancer and she turns out to actually have cancer, there is a much higher chance that she will need more than a hysterectomy as treatment. Only less aggressive endometrial cancers that have not spread deeply into the muscle of the uterus can be treated with hysterectomy alone. More invasive or aggressive cancers need additional therapy such as radiation or chemotherapy. They also require more extensive surgery such as lymph node removal near the major blood vessels and biopsies. This often requires surgery by specially trained gynecologic oncologists (cancer surgeons).

PAP Smear Recommendations

By Frederick R. Jelovsek, M.D.,
Quillen College of Medicine -- Department of Obstetrics and Gynecology
East Tennessee State University

How often is a PAP smear necessary? Different doctors and organizations have different answers. A 1996 conference as recently reported in: Braly, P.S., The NIH consensus conference on cervical cancer: Implications for practice. Primary Care Update for Ob/Gyns 1997 (4):179-183, gave some consensus guidelines.

PAP smears should be started when sexual activity starts or at age 18, whichever is earlier. Three annual PAP smears should performed and after that, smears can be less than annually if a patient is low risk. Few women qualify as low risk, meaning no more than two lifetime sexual partners and a partner with no more than two lifetime partners. Thus many women should continue to have a yearly PAP smear and after age 65, all women should have an annual exam.

Other risk factors for cervical cancer include smoking, lower socioeconomic status, age, having had multiple pregnancies, immunosuppression, and sexually transmitted diseases - especially human papilloma virus (HPV) which is found in 100% of cervical cancers. Certain strains of HPV, types HPV-16, -18, -31, and -45, are high risk and account for 80% of cervical cancer. In spite of this knowledge, there is still no consensus about screening patients who have abnormal PAP smears for these HPV virus types. Studies are ongoing to see if this additional screening in addition to the PAP smear is cost-justified. Most investigators believe that it not only takes years for the progression from HPV infection to malignancy but that it is apparent that the infection alone is not sufficient for the development of cervical cancer. Other cofactors are needed in addition to HPV. Tobacco carcinogenic and mutagenic substances, compromised immune status, dietary deficiencies, radiation exposure and coexisting viral and bacterial infections are thought to somehow enhance a malignant transformation.

It is estimated that as many as 5-20% of persons 15-49 years old are infected with HPV. Vaccines against HPV are currently being developed but they are not going to be available in the near future. If you have ever had abnormal PAP smears or had venereal warts (HPV infection, condyloma accuminata), you should be sure to get an annual PAP smear for the rest of your life.

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