Evolution of the Pap smear: Public health success story

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In May, Dr. Georgios Papanikolaou was recognized for his revolutionary research in cervical cancer screening and prevention, even appearing on the Google doodle on May 13. Approximately 570,000 cases of cervical cancer were diagnosed in 2018 alone,3 and mortality rates have greatly dropped since the 1930s, thanks to Papanikolaou's discovery.

In 1928, Papanikolaou's research lead him to conclude that uterine cancer could be discerned from a vaginal smear. This later informed his work with Dr. Aurel BabeČ™ and the invention of the Pap smear.

The next few years saw the American Cancer Society endorse the use of the Pap smear in cervical cancer screening programs all around the world. Between 1955 and 1980, the incidence rate of cervical cancer dropped phenomenally, by 70% to 85%, in the areas where screening was adopted.4

Drs. Georgios Papanikolaou (left) and Aurel BabeČ™ (right).Drs. Georgios Papanikolaou (left) and Aurel BabeČ™ (right).

So, what's the process for cervical cancer screening? In a traditional Pap smear, a gynecologist scrapes cells from the cervix and transfers them directly onto a microscope slide that is sent to a cytologist or pathologist.2 The cytologist or pathologist then stains the cells with a Pap stain and observes the cells under a microscope lens, reporting the findings using the Bethesda system:1

  • Negative for intraepithelial lesion or malignancy -- no signs of cancerous cells, but the scrape may show other signs of infection
  • Epithelial cell abnormalities -- the cells lining the cervix indicate a cancer or precancer condition:
    • Low-grade squamous intraepithelial lesion (LSIL): mild abnormality
    • High-grade squamous intraepithelial lesion (HSIL): high abnormality; needs treatment
  • Other malignant neoplasms -- other cancers that don't often affect the cervix

The traditional Pap smear, though effective, has its limitations. It has a broad range of sensitivity (meaning it detects cells other than the targets) and a false-negative rate between 14% and 33%.4

Hologic's ThinPrep test.Hologic's ThinPrep test.

Naturally, the procedure has since evolved to accommodate these shortcomings. Most clinics now use liquid-based cytology (LBC). Here, the cell sample is similarly obtained; however, instead of being smeared directly onto a slide, the sample is added to a vial with a preservative medium and then transferred to the laboratory.4 Once this sample has been processed within the medium, it is transferred to a cell spot on a microscope slide.

What are the benefits of LBC? It essentially removes the debris (red blood cells, mucus, etc.) and preserves the cells of importance, improving sample quality and sensitivity to greater than 93%. Additionally, the "monolayer [generated] may be analyzed by a computer-based imager and reviewed by a cytotechnologist and/or pathologist."4

In 1996, Hologic launched the first test approved by the U.S. Food and Drug Administration (FDA) for both Pap and HPV testing: its ThinPrep Pap test. This LBC provides the benefit of co-testing -- only one cell sample is required, with no need to scrape for cells twice.5 The ThinPrep system has three simple steps once the sample is introduced: The filter is rotated to separate the debris from the cells on the brush, the cells are collected on the membrane of the filter, and the filter is inverted and pressed to the microscope slide.

Becton Dickinson's SurePath test.Becton Dickinson's SurePath test.

Becton Dickinson launched its FDA-approved SurePath test in 1999, just a few years after Hologic's release. SurePath offered not only great improvements in detecting the presence of cancerous cells but also both types of precursor lesions, compared with the traditional Pap test.4 With SurePath, the sample is collected "via a broom-like device or combination brush/spatula with detachable heads and then placed in a vial with [the SurePath preservative fluid]." The sample then undergoes enrichment through a sedimentation process and is centrifuged into a pellet. Part of the pellet is then observed under a microscope.

Several studies have been conducted to compare each of these tests against the traditional Pap test. The ThinPrep test has been shown to increase LSIL detection by 65%, while SurePath has been shown to increase LSIL detection by 47% and HSIL detection by 116%.4

Each test has a different cell preparation procedure and advantage. One study conducted by Rozemeijer et al in 2016 suggested that these differences could arise due to cell preparation -- the cell yield is higher when the collecting device is retained in SurePath versus ThinPrep, where cells are rinsed off and preserved separately. However, SurePath has not been approved for HPV screening.

While these differences exist, it's clear that liquid-based cytology provides more accurate screening than the traditional Pap smear, and LBC has widely replaced the traditional test as the primary test for cervical cancer screening.

Cervical cancer screening has come a long way in the past century. Microscopes and accompanying imaging software have vastly improved efficiency and accuracy. One thing is for sure: The invention of the Pap smear by the innovative scientists Drs. Georgios Papanikolaou and Aurel BabeČ™ has helped many women over the years.


  1. The Pap (Papanicolaou) test. American Cancer Society website. https://www.cancer.org/cancer/cervical-cancer/prevention-and-early-detection/pap-test.html. Published December 9, 2016. Accessed June 4, 2019.
  2. Pap test. Cancer.Net website. https://www.cancer.net/navigating-cancer-care/diagnosing-cancer/tests-and-procedures/pap-test. Published June 2018. Accessed June 4, 2019.
  3. Cervical cancer. World Health Organization website. https://www.who.int/cancer/prevention/diagnosis-screening/cervical-cancer/en/. Accessed June 4, 2019.
  4. Gibb RK, Martens MG. The impact of liquid-based cytology in decreasing the incidence of cervical cancer. Rev Obstet Gynecol. 2011;4(Suppl 1):S2-S11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3101960/. Accessed June 4, 2019.
  5. Rozemeijer K, Penning C, Siebers AG, et al. Comparing SurePath, ThinPrep, and conventional cytology as primary test method: SurePath is associated with increased CIN II+ detection rates. Cancer Causes Control. 2016;27:15-25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703623/. Accessed June 4, 2019.

Monika Mahajani is a content marketing associate with the Science Advisory Board (SAB), an international community of scientific and medical experts across hundreds of countries and disciplines. More information is available on SAB's website.

Disclosure: LabPulse.com is a sister company of the Science Advisory Board.