Cervical (pap) smear: New directions

Abstract

This article reports the historic background leading to the introduction of cervical smears as a tool in the detection of precancerous changes in the uterine cervix. The false-negative error rate in the primary screening process is discussed and illustrated by data recently compiled from this laboratory. Rescreening of approximately 25% of cervical smears yielded an error screening rate of approximately 5% of precancerous lesions and cancer of the uterine cervix. The total false-negative screening error rate was much higher but was unknown and should be determined by additional studies. The reasons for the false-negative screening errors are discussed. Some of the proposed remedies, particularly screening of the entire population for human papillomavirus infection, are judged to be unacceptable because of the high prevalence of this virus in well women and because the biologic events linking the presence of viral DNA with the development of precancerous lesions are unknown. Screening assistance with the help of a newly developed interactive machine, combining image analysis with a neural net was promising as a tool in quality control. tended by approximately 90 interested gynecologists and pathologists. I wish that I could say that this conference offered an unequivocal endorsement of the smear as a tool for cancer prevention, but this was not the case. In fact, the senior pathologists of the day attending the conference expressed significant reservations about the cytologic approach to the diagnosis of cancer. It is reliably reported that my former chief, the late Dr. Fred W. Stewart, then the head of Pathology at the Memorial Hospital for Cancer and Allied Diseases (the Sloan Kettering Institute was still in the planning stage at that time), declared that "a biopsy was better." With the passage of time, Stewart' changed his opinion about the value of the smear and, in his last article published in 1971, and characteristically entitled "Retirement in New York: Prognosis and Reminiscences of a Nonoptimist," he had this to say, "I suspect that in the field of service-to-the-patient pathology-if we leave out the great contribution of cytology toward early diagnosis (italics, L.G.K.)-about all the progress we have made involves the correction of old errors."Papanicolaou's sampling technique, initially developed to study the hormonal status of mice, was a vaginal pool smear, and this was the method originally used in clinical observations on ~o m e n .~,~ Microscopic examination of the vaginal smear was tedious, time consuming, and required the most careful screening of the material, searching for a few abnormal cells as evidence of cervical cancer or precancerous states. It was not surprising, therefore, that when the Canadian gynecologist and ardent follower of Papanicolaou, J. Ernest Ayre,' proposed that a wooden tongue depressor, cut to fit the contour of the uterine cervix, would allow a direct sampling of this organ under visual control the method was endorsed enthusiastically. The direct cervical smear was eas...

Plasma proteomic analysis of patients with squamous cell carcinoma of the uterine cervix

“…In addition, the infrastructure for Pap smear screening is not well established in most developing countries. [3][4][5] Although colposcopy-guided biopsy and cone biopsy for histological examination can be used to diagnose cervical cancer, they are expensive procedures that require specific skills to perform. 6 Therefore, the discovery of biomarkers for simple, inexpensive, and widespread testing in developing countries is needed for the screening, early detection, and post-treatment surveillance of cervical cancer.…”

Correlation of promoter hypermethylation in hTERT, DAPK and MGMT genes with cervical oncogenesis progression

“…Cytomorphological examination of cervical smears is most widely applied, although Pap smear has false negative rates of 2-40%, due to a combination of sampling error, processing artifacts and the nature of subjective interpretation (8). HPV testing has been suggested to improve cervical cancer screening, however its specificity remains relatively low (9).…”

Validity of Colposcopy in the Diagnosis of Early Cervical Neoplasia: A Review

“…[6][7][8][9] This is largely attributed to errors of sampling and interpretation. [10][11][12] Eventually, the complementary use of cytology and colposcopy for the identification and evaluation of women at risk of cervical intraepithelial neoplasia and its precursors was thought to secure the highest yield of detection of cervical neoplasia. 13,14 The management strategy for women with abnormal cervical smears varies widely.…”