Dr. Alan G. Waxman MD, MPH (University of New Mexico), and Dr. Kenneth Noller, MD (New England Medical Center Boston, Massachusetts), both dealt with the issue of changes in cytology screening and the role of human papillomavirus (HPV)-DNA testing. Invasive cervical cancer has been reduced by 70% in the United States through the use of cervical cytology. There has never been a national screening program here; rather, patients are screened opportunistically. Thus, the affluent are often over-screened and the indigent are under-screened. Most women with cervical cancer either have never been screened or have not had a Pap test in at least 5 years. Although we will never be able to detect every case of cervical cancer, the majority would be identified if there were universal testing.
Variations in Cervical Screening Guidelines -- When Should Screening Commence?
Guidelines for cervical cancer screening from The American College of Obstetricians and Gynecologists (ACOG), The American Cancer Society (ACS), and the U.S. Preventive Services Task Force (USPSTF) have all been recently published. Dr. Waxman noted that the different agencies recommend much that is similar. ACOG Practice Bulletin #45 recommends beginning screening no later than age 21 or approximately 3 years after onset of vaginal intercourse. However, he stressed the importance of providing appropriate preventive healthcare to adolescents not yet requiring a Pap test, such as screening for sexually transmitted infections and contraceptive counseling.
The reason why the recommendation to initiate cervical screening with onset of sexual activity was changed to initiation 3 years after onset of sexual activity is because although the cervix is extremely vulnerable to HPV infection in adolescence, this infection is usually transient and usually clears in 1 to 2 years. In addition, most dysplasias in the adolescent regress spontaneously. Most importantly, cancer develops over years and is rare in the first 2 decades of life or within 3 years of onset of intercourse. Lastly, by limiting the screening in these patients who are highly susceptible yet for the most part who only have transient dysplasia will reduce the anxiety and morbidity from unnecessary follow-up procedures.
Why even designate an age limit of 21? The ACS rationale is that providers may not get an adequate sexual history. Adolescents also may be unwilling to disclose prior consensual or nonconsensual intercourse. Dr. Waxman made sure to point out that there is still room for individualization of screening. ACOG's practice bulletin acknowledges the "unpredictable nature of follow-up in younger women," and therefore states that screening may be started earlier at the physician's discretion. The ACS also states that "Provider discretion and patient choice should guide screening in women ≥21 who have never had vaginal intercourse."
When Is it Appropriate to Cease Cervical Screening?
Differences in opinion exist, however, with regard to when to stop screening women. The USPSTF recommends against routine screening after age 65 if recent screening has been adequate, normal Pap test results were obtained, and the patient is not otherwise at high risk for cervical cancer. The ACS recommends that women with an intact cervix may elect to discontinue screening at age 70 or older after they have had 3 or more documented consecutive satisfactory negative Pap test results and no abnormal Paps within the 10 years before age 70 and if they are at low risk and in good health. ACOG states that evidence is too inconclusive to set an upper age limit for cervical cancer screening. However, if screening is discontinued, it is recommended that risk factors be assessed during annual exam to determine whether restarting screening is appropriate.
The logic for setting upper limits for age for cervical cancer screening is that the incidence of cervical cancer plateaus at about age 65 for most US women and that new cervical cancers in older women are mostly seen in unscreened and under-screened women. By way of example, in a cohort of 2561 postmenopausal women who participated in the Heart Estrogen/progestin Replacement Study (HERS) and who had gone 1 to 2 years without screening after having a negative Pap, 110 required diagnostic work-ups for abnormal Paps. This led to 231 interventions all to find a single case of mild-to-moderate dysplasia. We must consider the morbidities associated with false-positive tests, which include anxiety, discomfort, and increased health costs. Notably, in a survey of ACOG physicians conducted by Dr. Noller, 74% never stop doing Paps.
Screening vaginal cytology after hysterectomy, as per the ACOG recommendations, may be discontinued in women who have had a total hysterectomy for benign indications. However, if a woman has had prior cervical intraepithelial neoplasia (CIN) 2 or 3, annual screening should be continued until 3 consecutive negative smears are obtained. These recommendations are based on the fact that vaginal cancer is extremely rare. A study by Pearce found no significant pathology in 9610 patients post vaginal hysterectomy even though 1.1% had abnormal cytology; almost all were false positives.
What Is the Appropriate Screening Interval?
The next issue broached was the safety of increasing the intervals between Pap smears. It seems that previously well-screened women are at little risk of developing squamous cancer within 3 years of their last negative Pap. The incidence of CIN 2+ in women with at least 3 prior negative screening tests according to the National Breast and Cervical Cancer Program is extremely low, with no cancers identified and only 16 cases of CIN 2+ out of 32,230 women screened (0.05%). Numerous studies have shown little difference in detection of new cancers with 1-, 2-, or 3-year screening intervals. This along with the potential harm, inconvenience, and cost from over-screening have made this issue quite pertinent. Sawaya and colleagues have calculated that 209,000 Paps and 11,502 colposcopies would need to be done in women aged 45 to 60 with 3 negative prior Paps to prevent a single case of cervical cancer.ACOG Practice Bulletin #45 still allows room to individualize screening interval, depending on the weight of risk factors, ability to determine past screening history, and ability to monitor the patient in the future. Yearly testing may be warranted in individual cases and remains acceptable. Most agree that women younger than 30 years of age should be screened yearly. It would be reasonable to extend the screening interval to 2 to 3 years for a woman older than 30 if she has had 3 consecutive negative Paps. High-risk populations (eg, HIV positive, immunosuppressed, DES exposed, high-grade dysplasia in the past) should be closely followed.
Primary Screening With Pap and HPV-DNA Testing
Primary screening with Pap and HPV has recently been approved by the US Food and Drug Administration (FDA). Primary testing with high-risk HPV DNA plus Pap is appropriate for primary screening in women older than age 30 at a frequency of no more than every 3 years. The negative predictive value approaches 100%. In an interesting study by the Kaiser group,it was determined that if both Pap and high-risk HPV-DNA results for a given woman were negative, the negative predictive value for her not having CIN 3 at 5 years was 99.84%. If HPV causes cervical cancer, one might wonder, why not just screen everyone with HPV DNA? The answer is that HPV is a young person's infection affecting many women younger than 30. As mentioned earlier, most HPV infections do not translate into high rates of severe dysplasia and most are spontaneously cleared. Cervical cancer affects older women who have persistent infection. Although HPV-DNA testing is very sensitive for identifying patients who will have CIN 2 or greater, its specificity is not as good as Pap alone, and its positive predictive value is poor.In patients older than 30, however, the sensitivity (86%) and specificity (83%) of HPV testing are much more acceptable.
Summary- Although invasive cervical cancer has been reduced by 70% in the US through the use of cervical cytology, there has never been a national screening program here; rather, patients are screened opportunistically. Thus, the affluent are often over-screened and the indigent are under-screened.
- Guidelines for cervical cancer screening from ACOG, ACS, and the USPSTF have all been recently published. The guidelines vary slightly with respect to when to commence screening and when to cease.
- Generally, patients younger than 30 years of age should be screened yearly, but it would be reasonable to extend the screening interval to 2 to 3 years for a woman older than 30 if she has had 3 consecutive negative Paps. Primary testing with high-risk HPV DNA plus Pap is appropriate for primary screening in women older than age 30 at a frequency of no more than every 3 years.
References :
1. ACOG Practice Bulletin: Clinical management guidelines for obstetrician-gynecologists. 2. Saslow D, Runowicz CD, Solomon D, Moscicki AB, Smith RA, Eyre HJ, Cohen C; American Cancer Society. American Cancer Society guideline for the early detection of cervical neoplasia and cancer.
3.Pearce KF, Haefner HK, Sarwar SF, Nolan TE. Cytopathological findings on vaginal Papanicolaou smears after hysterectomy for benign gynecologic disease. N Engl J Med.
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