The Role of the Pap Smear in Cervical Screening

The Papanicolaou test, commonly known as a Pap smear, has been the cornerstone of cervical cancer screening for decades. It is a cytological test designed to detect abnormal cells on the cervix before they progress to invasive cancer. By identifying and treating cervical dysplasia early, the Pap smear has drastically reduced cervical cancer incidence and mortality worldwide.

How the Test Works

During a routine pelvic exam, a healthcare provider uses a small brush or spatula to gently scrape cells from the transformation zone of the cervix—the area where squamous and glandular cells meet, which is most vulnerable to HPV infection. These cells are preserved in a liquid medium (liquid-based cytology) and sent to a laboratory, where a cytotechnologist or pathologist examines them under a microscope for structural abnormalities indicative of viral damage or precancerous changes.

Understanding the Bethesda System

Laboratories report Pap smear results using the Bethesda System, a standardized terminology that categorizes cellular abnormalities:

• Negative for Intraepithelial Lesion or Malignancy (NILM): Normal results; no signs of dysplasia or cancer.
• ASC-US (Atypical Squamous Cells of Undetermined Significance): The most common abnormal result. Cells appear slightly abnormal, often due to a transient HPV infection or inflammation.
• LSIL (Low-grade Squamous Intraepithelial Lesion): Mild abnormalities often corresponding to early or transient HPV infections (roughly equivalent to CIN 1).
• HSIL (High-grade Squamous Intraepithelial Lesion): More severe abnormalities indicative of a higher risk for progressing to cancer (roughly equivalent to CIN 2 or CIN 3).
• AGC (Atypical Glandular Cells): Abnormalities in the glandular cells of the cervix or uterus, requiring specialized follow-up.

Accuracy, Co-testing, and Next Steps

While the Pap smear is highly effective, it relies on human interpretation and can have false-negative results. To increase accuracy, clinical guidelines often recommend co-testing—performing an HPV DNA test alongside the Pap smear for patients over 30. An abnormal Pap smear is typically followed up with a colposcopy to visually evaluate the cervix and obtain tissue biopsies for a definitive histological diagnosis.

The Papanicolaou test (abbreviated as Pap test, also known as Pap smear (AE), cervical smear (BE), or smear test (BE)) is a method of cervical screening used to detect potentially precancerous and cancerous processes in the cervix (opening of the uterus or womb) or, more rarely, anus (in both men and women). Abnormal findings are often followed up by more sensitive diagnostic procedures and, if warranted, interventions that aim to prevent progression to cervical cancer.

The test was independently invented in the 1920s by the Greek physician Georgios Papanikolaou and named after him. A simplified version of the test was introduced by the Canadian obstetrician Anna Marion Hilliard in 1957. A Pap smear is performed by opening the vagina with a speculum and collecting cells at the outer opening of the cervix at the transformation zone (where the outer squamous cervical cells meet the inner glandular endocervical cells), using an Ayre spatula or a cytobrush.

The collected cells are examined under a microscope to look for abnormalities. The test aims to detect potentially precancerous changes (called cervical intraepithelial neoplasia (CIN) or cervical dysplasia; the squamous intraepithelial lesion system (SIL) is also used to describe abnormalities) caused by human papillomavirus, a sexually transmitted DNA virus. The test remains an effective, widely used method for early detection of precancer and cervical cancer.

While the test may also detect infections and abnormalities in the endocervix and endometrium, it is not designed to do so. Guidelines on when to begin Pap smear screening are varied, but usually begin in adulthood. Guidelines on frequency vary from every three to five years. If results are abnormal, and depending on the nature of the abnormality, the test may need to be repeated in six to twelve months.

If the abnormality requires closer scrutiny, the patient may be referred for detailed inspection of the cervix by colposcopy, which magnifies the view of the cervix, vagina and vulva surfaces. The person may also be referred for HPV DNA testing, which can serve as an adjunct to Pap testing. In some countries, viral DNA is checked for first, before checking for abnormal cells.

Additional biomarkers that may be applied as ancillary tests with the Pap test are evolving. Screening guidelines vary from country to country. In general, screening starts about the age of 20 or 25 and continues until about the age of 50 or 60. Screening is typically recommended every three to five years, as long as results are normal. American Congress of Obstetricians and Gynecologists (ACOG) and others recommend starting screening at age 21.

Many other countries wait until age 25 or later to start screening. For instance, some parts of Great Britain start screening at age 25. ACOG's general recommendation is that people with female reproductive organs age 30–65 have an annual well-woman examination, that they not get annual Pap tests, and that they do get Pap tests at three to five year intervals.

HPV is passed through skin to skin contact; sex does not have to occur, although it is a common way for it to spread. It takes an average of a year, but can take up to four years, for a person's immune system to clear the initial infection. Screening during this period may show this immune reaction and repair as mild abnormalities, which are usually not associated with cervical cancer, but could cause the patient stress and result in further tests and possible treatment.

Cervical cancer usually takes time to develop, so delaying the start of screening a few years poses little risk of missing a potentially precancerous lesion. For instance, screening people under age 25 does not decrease cancer rates under age 30. HPV can be transmitted in sex between females, so those who have only had sex with other females should be screened, although they are at somewhat lower risk for cervical cancer.

Guidelines on frequency of screening vary—typically every three to five years for those who have not had previous abnormal smears. Some older recommendations suggested screening as frequently as every one to two years, however there is little evidence to support such frequent screening; annual screening has little benefit but leads to greatly increased cost and many unnecessary procedures and treatments.

It has been acknowledged since before 1980 that most people can be screened less often. In some guidelines, frequency depends on age; for instance in Great Britain, screening is recommended every three years for women under 50, and every five years for those over. Screening should stop at about age 65 unless there is a history of abnormal test result or disease.

There is probably no benefit in screening people aged 60 or over whose previous tests have been negative. If a woman's last three Pap results were normal, she can discontinue testing at age 65, according to the USPSTF, ACOG, ACS, and ASCP; England's NHS says 64. There is no need to continue screening after a complete hysterectomy for benign disease.

Pap smear screening is still recommended for those who have been vaccinated against HPV since the vaccines do not cover all HPV types that can cause cervical cancer. Also, the vaccine does not protect against HPV exposure before vaccination. Those with a history of endometrial cancer should discontinue routine Pap tests after hysterectomy. Further tests are unlikely to detect recurrence of cancer but do bring the risk of giving false positive results, which would lead to unnecessary further testing.

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