Cervical Cancer Questions & Answers

Why screen for cervical cancer?

A successful screening program must fulfill three criteria:

(1) The disease must have high incidence, morbidity, and mortality;

(2) the screening test should be sensitive, inexpensive, and widely available; and

(3) early detection and treatment must affect morbidity and mortality. The Papanicolaou (Pap) smear meets all these requirements.

Prior to 1943, when universal screening programs began in the United States, cervical cancer was the most frequently diagnosed cancer in women. Recent data estimate that 73 percent of women who receive their health care through HMOs have had a Pap smear within the last three years. Unfortunately, the percentage of women screened is lower among minorities, the elderly, and those covered by Medicare or having no medical insurance.

What is the effect of early detection?

More than 90 percent of patients whose cervical cancer is localized (stage I) at diagnosis are alive five years later, while only 14 percent of those with metastatic disease (stage IV) at diagnosis are alive at five years. Because increasing percentages of women are being screened and precancerous lesions are better detected and treated, the mortality of invasive cervical cancer has decreased approximately 60 percent in the past 60 years.

When should the first Pap smear be done?

Cervical cancer screening should begin when the risk for precancerous lesions begins--at age 18 or at the initiation of sexual activity, whichever is earlier. Every woman who is now or who has ever been sexually active should be screened, including those once believed not to be at risk, such as lesbians.

How frequently should a woman be screened?

The American Cancer Society, the American College of Obstetricians and Gynecologists, and the U.S. Preventive Services Task Force recommend annual Pap smears until a woman has had two or three consecutive negative results. The physician should then recommend a screening interval of from one to three years, depending on the patient's risk factors.

Women with a normal pelvic examination and negative Pap smears who are deemed "high risk" based on factors shown in Table 1 should be screened annually. Immunocompromised HIV-positive patients (CD4+ cell count <500/muL) may even need biannual screening.

Low-risk patients who have a Pap smear every two or three years do not need an annual pelvic examination unless it is indicated for another reason, such as pelvic pain. The bimanual pelvic examination is not a recommended screening tool for detection of ovarian cancer except in women with a strong family history of breast or ovarian cancer.

Do elderly women require screening?

Pap smears may be discontinued after age 65 in women who have been adequately screened in the past because continued screening has minimal effect on cervical cancer mortality. This decision, however, should be individualized. For example, a 65-year-old woman with severe congestive heart failure and metastatic lung cancer would not benefit from further screening because of her shortened life expectancy. However, an active and healthy 65-year-old with no comorbid conditions might benefit from identification and treatment of a lesion that could progress to invasive cervical cancer in her predicted lifetime.

Despite ongoing screening programs, invasive cervical cancer and mortality from cervical cancer are common in elderly women, partly because of the gradual natural progression of the disease. More importantly, case-control studies show that, compared with controls, women with invasive cervical cancer were more likely never to have been screened. The American College of Physicians recommends screening for women older than 65 if they have not had a Pap smear in the last 10 years. These women should be screened at three-year intervals until they have had three negative smears or until the cost of further screening has exceeded the benefit of life expectancy.

Is screening needed after hysterectomy?

There is no simple answer to this question. In fact, women who have had hysterectomies can be divided into three categories:

(1) A woman who has had a hysterectomy for benign reasons and who has no history of abnormal Pap smears or abnormal pathology in the hysterectomy specimen is no longer at risk for cervical cancer and needs no further screening. Vaginal cancer is a rarity in the general population, and most experts do not recommend mass screening by doing vaginal smears in low-risk, asymptomatic women for vaginal dysplasia.

(2) A woman who has had a subtotal, supracervical hysterectomy (i.e., her cervix remains) can still develop cervical cancer and should be screened every one to three years, depending on her risk factors.

(3) A woman who has undergone a total hysterectomy for cervical cancer or who has had cervical cancer found incidentally on pathology or at any time in the past is at increased risk for vaginal and vulvar cancer. These women should have smears done every six months for the first one to two years. After that, the rate of vaginal neoplasia returns to that of women with no history of cervical cancer. The opinions of experts range from "screen annually" to "screen every three years" to "do not screen any asymptomatic woman." These conflicting opinions reflect the lack of cost-effectiveness in screening a population that may be only at marginally greater risk of a fairly rare disease.

When is the ideal time for a Pap smear?

In general, Pap smears should not be done when a woman is menstruating or when she has a vaginal infection because blood or inflammatory cells may obscure the cellular field and lead to an inaccurate reading. Expert groups also recommend abstinence from sexual intercourse, vaginal creams, douches, or tampons for 24 hours prior to the examination to minimize alterations in the vaginal pH, mucosal appearance, etc. However, there are no strong experimental data showing that these factors limit the accuracy of the smear, nor is there strong evidence showing that lubrication of the speculum adversely affects accuracy. If lubrication is necessary to ease insertion of the speculum, warm water may be adequate. If it is not, a minimal amount of a water-based lubricant should be used rather than cause the patient pain.

Patient discomfort should be minimized. Women should empty their bladders to decrease pelvic pressure from a full bladder and to reduce the urge to urinate while the smear is taken. Telling the patient about each step during the procedure is helpful.

How is a Pap smear done?

Tissue samples are collected with a spatula and an endocervical brush (which replaced the cotton swab), smeared onto one or two glass slides, and quickly sprayed with or placed in liquid fixative. To simplify the process and decrease inaccurate reports due to premature cellular dehydration, a new technique has been developed: Cervical cells are collected as with the traditional system, using the spatula and brush, then scraped together into a single vial already containing chemical preservative.

Several studies show that this newer method may increase detection of infections as well as more serious cellular abnormalities. This method may also decrease the number of unsatisfactory specimens and, perhaps most important, decrease the number of patients who have benign biopsies on follow-up colposcopy. The vial contains hemolytic agents that prevent blood from obscuring the accuracy of the evaluation and may allow the physician to perform a Pap at any point in the patient's menstrual cycle. This system is still in its earliest stages of use, however, and needs to be evaluated after it has been used on a large scale.

What should be done if the cervix appears abnormal or if there is bleeding from the cervical os during or after the Pap smear?

Several benign conditions, such as pregnancy, hormonal changes, or infection, can make the cervix appear "abnormal" to the general practitioner (Figures 1A to 1C). Cervical ulcerations or erosions, a fragile or inflamed epithelium, or large and branching blood vessels are strongly suggestive of squamous or adenocarcinoma of the cervix (Figure 2) and mandate referral for colposcopy and possible treatment.

It is common for women to have a small amount of bleeding from the cervical os after the endocervical brush is used. Patients should be advised of this and provided sanitary pads to minimize damage to clothing from spotting. Although spotting after a Pap smear is normal, a full history and physical examination should be done if a patient complains of postcoital or other dysfunctional menstrual bleeding.

How are "abnormal" Pap smears classified?

The Bethesda system of cervical cancer classification was developed by the National Cancer Institute to increase standardization of Pap smear categories and to allow comment on sample adequacy and hormonal state of the epithelium. This newer classification system attempts to improve upon the prior cervical intraepithelial neoplasia (CIN) system by differentiating cases of epithelial proliferation, including low-grade squamous intraepithelial lesion (LGSIL), from definite premalignant conditions or high-grade squamous intraepithelial lesion (HGSIL). Low-grade squamous intraepithelial proliferation ranges from cellular changes of human papillomavirus up to the prior CIN I (mild dysplasia) category, while high-grade lesions include CIN II and III (moderate to severe dysplasia) and carcinoma in situ (CIS). It is strongly recommended that all laboratories use the Bethesda system of classification.

What does the cytopathologist look for?

Under the Bethesda system (Table 2), a specimen may be considered inadequate if the field is obscured by blood from a sample obtained during menstruation or if no endocervical cells are seen. Such smears should be repeated at the patient's earliest convenience. A good sample often requires rotating the cytobrush 360 degrees after the entire length of the bristles is within the endocervical canal. This is especially true in older women whose squamocolumnar junction has regressed into the endocervical canal.

Benign cellular changes have been subdivided into infectious and benign reactive changes. Cytopathologists are often able to see Trichomonas vaginalis, Candida or Actinomyces organisms, coccobacilli associated with bacterial vaginosis, or cellular changes consistent with the herpes simplex virus. Other infectious agents, such as Neisseria gonorrhoeae or chlamydia, may cause only an inflammatory cellular reaction. Patients with infections should be treated and their Pap smears repeated after completion of treatment. Benign reactive changes may be associated with inflammation from infection, atrophy, radiation exposure, or an intrauterine device. These changes require no treatment.

The classification scheme for squamous cell abnormalities is divided into four categories: (1) atypical squamous cells of undetermined significance (ASCUS), (2) LGSIL, (3) HGSIL, and (4) carcinoma.

Glandular cell abnormalities comprise reportable changes ranging from benign postmenopausal changes to atypical glandular cells of undetermined significance (AGCUS) to adenocarcinoma (endocervical or endometrial).

The cytopathologist also analyzes the hormonal environment of the vaginal mucosa, reported as showing a hormonal pattern compatible or incompatible with the patient's age and/or history. Women in an estrogen-deficient state may be treated with topical estrogen creams or oral estrogen to minimize symptoms and have another Pap smear scheduled three to six months later.

Does every abnormal Pap smear require referral?

No. In healthy women, many early lesions will actually regress, and follow-up cervical smears will become normal without any intervention. Women who have ASCUS or possibly even LGSIL need only a repeat Pap smear done by their primary-care physician after six months. The ideal follow-up for LGSIL is controversial. Some experts advise referral after a single Pap smear with LGSIL, while others look for persistent LGSIL on repeat smears. Until ongoing studies resolve this issue, physicians should follow the guidelines of their institutions. Aggressive cervical disease is believed to progress only slightly, if at all, in a six- to 12-month interval, and there is very little risk in delaying treatment for that time period. One study found the median time for progression to more advanced disease was 86 months for LGSIL and 12 months for HGSIL. The patient must be informed and compliant and able to participate in the follow-up plan; patients who are noncompliant with follow-up should be referred earlier.

Who does need to be referred?

Though cervical cytology is adequate for identifying patients at risk for cervical cancer, Pap smears do not completely evaluate the cervix or the degree of disease. For this, the patient requires colposcopy. The colposcope is similar to a microscope which, focused through the speculum, provides a magnified view of the cervical epithelium. Biopsies can then be taken from areas that appear more abnormal.

Referral is warranted for the following:

    * Squamous cell carcinoma
    * HGSIL
    * LGSIL with a history of a higher-grade lesion
    * LGSIL that has persisted on repeat smears or a single LGSIL if that is the protocol for the particular institution
    * ASCUS that has persisted on two to three repeat Pap smears done at six-month intervals
    * HIV+ patients with CD4+ counts <500 cells/muL or other immunosuppressed patients with LGSIL or persistent ASCUS after three to six months
    * Adenocarcinoma of the cervix or any glandular lesion, including AGCUS. Unlike ASCUS, AGCUS has a high association with more severe disease. An estimated 20 percent of patients with AGCUS have either invasive cervical or uterine cancer.
    * Cervical abnormalities noted on physical examination or clinical symptoms suggestive of cancer.

Are advances still being made?

Pap smear sensitivity in cancer detection ranges from 50-98 percent, meaning that up to one half of cancers may be missed by this method. Various testing modalities, including cervical photography and screening colposcopy, have been studied in an attempt to improve cervical cancer detection, but none has been shown to be cost-effective. Certain strains of human papillomavirus (HPV) are associated with aggressive cervical dysplasia and cancer; patients infected with such a strain have a significantly greater risk of developing cervical dysplasia sometime during the following two years. One of the more promising methods employs hybridization of HPV DNA, but at the present time, HPV typing does not have predictive value in triaging ASCUS or other low-grade smears. Further refinement of HPV testing is likely in the near future.
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    * ACOG committee opinion. Recommendations on frequency of Pap test screening, Int J Gynaecol Obstet 49:210, 1995.
    * Flannelly G, Kitchener H. Every woman with an abnormal cervical smear should be referred for treatment: debate. Clin Obstet Gynecol 38:585, 1995.
    * Prendiville W, Walker P. Every woman with an abnormal cervical smear should not be referred for colposcopy: debate. Clin Obstet Gynecol 38:592, 1995.
    * Society of Gynecologic Oncologists Clinical Practice Guidelines: cervical cancer. Oncology 12:134, 1998.
    * U.S. Preventive Services Task Force. Guide to Clinical Preventive Services. 2nd ed. Published in 1996    

Table 1. Risk Factors Associated with Cervical Dysplasia And Cervical Cancer

    * Multiple (more than three) sexual partners or a partner with multiple partners
    * Intercourse at early age
    * History of cervical dysplasia or cervical cancer
    * Sexual partner who has had a partner with cervical cancer
    * History of human papillomavirus (HPV) or condylomata (genital warts)
    * History of herpes simplex virus (HSV) or other sexually transmitted disease
    * History of endometrial, vaginal, or vulvar cancer
    * Immunosuppression or HIV positivity (risk increases with decreasing CD4+ count)
    * Tobacco use (> 10-20 cigarettes/day) and/or alcohol or substance abuse
    * Lower socioeconomic status
    * Adapted from ACOG committee opinion. Recommendations on frequency of Pap test screening. Int J Gynaecol Obstet 49:210, 1995.

Table 2. Bethesda Classification of Cervical Cytology Used For Papanicolaou Smear

Adequacy--satisfactory or unsatisfactory

Benign cellular changes

Infectious: due to Trichomonas, Candida, and Actinomyces spp; herpes simplex virus; bacterial vaginosis

Reactive: inflammation, atrophy, radiation, intrauterine device

Squamous cell abnormalities

Atypical squamous cells of undetermined significance (ASCUS)

Low-grade squamous intraepithelial lesion (LGSIL)

High-grade squamous intraepithelial lesion (HGSIL)

Squamous cell carcinoma

Glandular cell abnormalities

Atypical glandular cells of undetermined significance (AGCUS)

Endocervical adenocarcinoma

Endometrial adenocarcinoma

Hormonal evaluation--hormonal changes of vaginal cytology