CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Barbara A. Crothers, DO
Rosemary Tambouret, MD
August 2014—The humble Pap test is perhaps one of the most lauded and disdained laboratory tests, lauded because it is the lab test with the best track record of preventing cancer and disdained because the test is labor-intensive, the results are operator dependent, and the regulations are burdensome. Recently the Pap test has come under fire, threatened to be replaced with HPV tests and maligned by patients and physicians for its sometimes unexpected high cost.
Dr. Crothers
When used appropriately, the Pap test is a remarkable laboratory test. In 1917, George Papanicolaou, MD, PhD, a research physician, was studying sex determination through cervical cell changes in guinea pigs. At that time, cervical cancer in women was a leading cause of cancer death, and Dr. Papanicolaou realized his method of cervicovaginal cell collection could be applied to human subjects to identify abnormal cells associated with cancer. In collaboration with Herbert Traut, MD, Dr. Papanicolaou discovered the Pap smear, and the newly formed American Cancer Society in 1948 encouraged its use in detecting and preventing cervical cancer.1 Now, the Pap test is used primarily to detect the presence of preneoplastic cells (high-grade squamous intraepithelial lesion [HSIL] or cervical intraepithelial neoplasia 2–3 [CIN2–3]) so that the precursor can be eradicated before it becomes invasive carcinoma. Since the Pap test’s inception, it has been beneficial in many other ways, including in evaluating hormonal status and in detecting infectious agents such as herpes simplex virus, Candida spp., Trichomonas vaginalis, Actinomyces spp., and bacteria associated with vaginosis. It was through observation of cellular changes in the Pap test that investigators, including Alexander Meisels, MD, first hypothesized the presence of a virus, human papillomavirus, as a possible etiologic agent inducing preneoplastic changes in squamous cells that define “dysplasia.”2 The Pap test has serendipitously been able to detect glandular neoplasms such as endometrial and endocervical carcinoma, and its precursor lesion, endocervical adenocarcinoma in situ—lesions that are often silent and difficult to detect clinically. It may also detect metastatic and recurrent carcinomas in the cervix or vagina of women with known cancer.
One reason for the Pap test’s tremendous success was the simple, oft-repeated message that all women should have the test yearly along with a pelvic examination. HPV tests have changed this paradigm, and current practice guidelines3,4 are more complex, incorporating a woman’s age, screening history, and HPV result into interval screening recommendations. Although the Pap test has an irreducible false-negative rate and is subject to interpretive error, its success is due in part to frequent opportunities to detect and eradicate cervical cancer precursors through annual screening. It can be a diagnostic test, but it is designed as a screening test to be used frequently to sample a large area of the cervix. How it might perform as a triage or diagnostic test is uncertain.