THE HISTORY OF THE PAP TEST

THE HISTORY OF THE PAP TEST

The pap test is considered by many to be the most cost effective cancer reduction program ever devised. Credit for its conception and development goes to George N. Papanicolaou, an anatomist and Greek immigrant to the Unites States. In 1928 he reported that malignant cells from the cervix can be identified in vaginal smears. Later, in collaboration with the gynaecologist Herbert Traut, who provided him with a large number of clinical samples, Papanicolaou published detailed descriptions of preinvasive cervical lesions. Pathologist and physicians initially greeted this technique with skepticism, but by the late 1940s Papanicolaou’s observations had been confirmed by others. The Canadian gynaecologist J. Ernest Ayre suggested taking samples directly from the cervix with wooden spatula rather than from the vagina with a pipette as originally described by Papanicolaou.” Eventually, cytologic smears were embraces as  an ideal screening test for preinvasive lesions, which, if treated, would be prevented from developing into invasive cancer.

                The first cervical cancer screening clinics were established in the 1940s,” The Pap test was never evaluated in a controlled, prospective study, but several pieces of evidence link it to the prevention of cervical cancer. First, the mortality rate from cervical cancer fell dramatically after screening was introduced, by 72% in British Columbia and 70% in Kentucky. Second, there was a direct correlation between the intensity of screening and the decrease in mortality. Among Scandinavian countries, the death rate fell by 80% in Iceland, where screening was greatest; in Norway, where screening was lowest, the death rate fell by only 10%. A similar correlation was observed in high and low screening regions of Scotland and Canada. In the United States, the decrease in deaths from cervical cancer was proportional to the screening rates in various states. Finally, women who do not develop invasive cancer are more likely to have had a Pap test than women with cancer. In Canadian study, the relative risk for women who had not had a Pap test for 5 years was 2.7, and screening history was a highly significant risk factor independent of other factors such as age, income, education, sexual history, and smoking. In Denmark, a woman’s risk of developing cervical cancer decreased in proportion to the number of negative smears she had had, by 48% with just one negative smear, 69% with two to four negative smears, and 100% with five or more smears.

                Screening guidelines differ around the world. Even in the United States, the recommendations of different organizations vary in some of their details. The American Cancer Society (ACS) recommends the following:

-          Cervical cancer screening should begin approximately 3 years after a woman begins having vaginal intercourse, but no later than 21 years of age.

-          Until age 30, cervical screening should be carried out every year with conventional Pap tests or every 2 years using liquid-based Pap tests.

-          At or after age 30, a woman who has had three normal test result in a row may be screened every 2 to 3 years with a Pap test (smear or liquid-based) or every 3 years with a Pap plus human papilloma virus (HPV) test.

-          A women 70 years of age and older has had three or more normal Pap test results and no abnormal results in the previous 10 years may choose to stop cervical cancer screening.

-          A women who has had a total hysterectomy  may choose to stop cervical cancer screening. [Exceptions are women with a history of CIN2,3, cervical cancer, or in utero diethylstilbestrol [DES] exposure.)

Women with a history of cervical cancer, in utero DES exposure, and who are immunocompromised (organ transplantation, chemotherapy, chronic corticosteroid treatment, or positive for human immunodeficiency virus (HIV) may benefit from more frequent screening. Adherence to these guidelines is critical for cervical cancer prevention. In the United States, more than 50% of women who develop cervical cancer have not had a Pap test in the 3 years before their cancer diagnosis.

The recent development of two prophylactic HPV vaccines provides a new opportunity for cervical cancer prevention. Both vaccines consist of empty protein shells called virus-like particles that are made up of the major HPV capsidprotein L1.They contain DNA AND ARE NOT INFECTIOUS. One of the vaccines, Gardasil (Merck & Co., Inc.), is a quadrivalent vaccine against HPV types 6, 11, 16, and 18. The other is the bivalent vaccine Cervarix (GlaxoSmithKline) that protects against HPV 16 and 18.They have shown extraordinary efficacy in preventing type-specific histologic CIN 2, 3 lesions, with no different in serious adverse effects compared to placebo. The vaccines are administered in three doses to females ages 9 to 26 years before the intiation of sexual activity. Continued Pap screening will remain important for many decades, however, because these vaccines do not protect against 30% of cervical cancers(i.e., those not related to HPV 16 or 18); the duration in treating prevalent HPV infections; and the cost of the vaccines light limit their use in some populations.

As seen in the aforementioned ACS recommendations, thecombination of a Pap test plus HPV test is included as an option for screening women 30 years of age or older. The rationale is to combine the superior sensitivity of HPV testing with the superior specificity of the Pap test. This recommendation is controversial because regarding the ideal management of women with discrepant results (e.g.,HPV test positive and Pap negative). The search for the best screening algorithm will undoubtedly continue, particularly as molecular diagnostic methods become more readily available.