What is a Pap smear test?

A Pap smear is a screening test for cervical cancer which detects both precancerous and cancerous lesions.^1,2 Pap smears have been instrumental in reducing morbidity and mortality from cervical cancer. Since the introduction of screening, there has been a steady decline in incidence and mortality, with rates of cervical cancer deaths dropping 50 to 70%.^1,3-5 Yet, despite this intervention, the risk of death from cervical cancer remains two times higher in black women compared to white women.⁶ Additionally, cervical cancer outcomes are worse among low-income women with limited access to healthcare.^7,8 More than 50% of cervical cancer cases in the United States occur in women who have never had screening, underscoring that access is critical for cancer prevention.⁹ Further, follow-up after initial screening is necessary to prevent subsequent cervical cancer development. In one study, out of 481 women with invasive cervical cancer, 23.5% had not had a pap smear in the last 5 years and 10.8% did not have proper follow-up after a prior abnormal Pap smear.¹⁰ 

During a Pap smear, a spatula or a brush is used to collect cells from the transformation zone of the cervix.^11,12 These cells are transferred to a microscope slide or a liquid-based medium for evaluation. Both conventional and liquid-based approaches have comparable performance.¹³ The cells are then evaluated under a microscope for abnormal changes associated with cancer, including nuclear enlargement, hyperchromasia, and irregular chromatin distribution and clumping.¹⁴ Additionally, if a liquid-based medium is used, testing for HPV DNA can be done.¹³ Results are categorized as: negative for intraepithelial lesion or malignancy, epithelial cell abnormalities, or other. Epithelial cell abnormalities include low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), atypical squamous cells (ASC), and atypical glandular cells (AGC). Cervical intraepithelial neoplasia (CIN), graded 1 – 3, can be used in place of, or in addition to, the squamous intraepithelial lesion interpretation.¹⁵ The ratio of nucleus to cytoplasm primarily defines the CIN grade, with higher ratios indicative of a higher grade.¹⁴

It is important to note that certain patient populations require more frequent pap smears because of associated conditions. In women who are immunosuppressed, such as those who have HIV or those who are on immunosuppressive medications, the risk of persistent HPV infection, and therefore cervical cancer development is higher.¹⁶ Additionally, women who were exposed to DES in utero have a higher cumulative risk of CIN 2 or worse compared to those who were not exposed.¹⁷ Therefore, screening should be done more frequently for these patient populations as the risk for the development of cervical cancer outweighs the potential harms.²

 ^References

1. Gustafsson L, Ponten J, Zack M, et al. International incidence rates of invasive cervical cancer after introduction of cytological screening. Cancer Causes Control 1997; 8 (5): 755-763.
2. Saslow D, Solomon D, Lawson HW, et al. American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. CA Cancer J Clin 2012; 62 (3): 147-172.
3. Mahlck CG, Jonsson H, Lenner P. Pap smear screening and changes in cervical cancer mortality in Sweden. Int J Gynaecol Obstet 1994; 44 (3): 267-272.
4. King A, Clay K, Felmar E, et al. The Papanicolaou smear. West J Med 1992; 156 (2): 202-204.
5. National Cancer Institute. SEER Cancer Stat Facts: Cervical Cancer. 2020; https://seer.cancer.gov/statfacts/html/cervix.html. Accessed July 24, 2020.
6. Collins Y, Holcomb K, Chapman-Davis E, et al. Gynecologic cancer disparities: a report from the Health Disparities Taskforce of the Society of Gynecologic Oncology. Gynecol Oncol 2014; 133 (2): 353-361.
7. Ramondetta LM, Meyer LA, Schmeler KM, et al. Avoidable tragedies: Disparities in healthcare access among medically underserved women diagnosed with cervical cancer. Gynecol Oncol 2015; 139 (3): 500-505.
8. Saghari S, Ghamsary M, Marie-Mitchell A, et al. Sociodemographic predictors of delayed- versus early-stage cervical cancer in California. Ann Epidemiol 2015; 25 (4): 250-255.
9. Spence AR, Goggin P, Franco EL. Process of care failures in invasive cervical cancer: systematic review and meta-analysis. Prev Med 2007; 45 (2-3): 93-106.
10. Janerich DT, Hadjimichael O, Schwartz PE, et al. The screening histories of women with invasive cervical cancer, Connecticut. Am J Public Health 1995; 85 (6): 791-794.
11. Schnippel K, Michelow P, Chibwesha CJ, et al. Cost-effectiveness of using the Cervex-Brush (broom) compared to the elongated spatula for collection of conventional cervical cytology samples within a high-burden HIV setting: a model-based analysis. BMC Health Serv Res 2015; 15: 499.
12. Practice Bulletin No. 168: Cervical Cancer Screening and Prevention. Obstet Gynecol 2016; 128 (4): e111-130.
13. Davey E, Barratt A, Irwig L, et al. Effect of study design and quality on unsatisfactory rates, cytology classifications, and accuracy in liquid-based versus conventional cervical cytology: a systematic review. Lancet 2006; 367 (9505): 122-132.
14. Martin CM, O'Leary JJ. Histology of cervical intraepithelial neoplasia and the role of biomarkers. Best Pract Res Clin Obstet Gynaecol 2011; 25 (5): 605-615.
15. Solomon D, Davey D, Kurman R, et al. The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA 2002; 287 (16): 2114-2119.
16. Ghebre RG, Grover S, Xu MJ, et al. Cervical cancer control in HIV-infected women: Past, present and future. Gynecol Oncol Rep 2017; 21: 101-108.
17. Hoover RN, Hyer M, Pfeiffer RM, et al. Adverse health outcomes in women exposed in utero to diethylstilbestrol. N Engl J Med 2011; 365 (14): 1304-1314.