Before the Pap smear was introduced in the 1940s by George Papanicolaou, after whom it was named, cervical cancer was the No. 1 killer of women in the United States. Now, the Pap smear has become a routine screening for women. For example, the Pap test can detect abnormal cell growth, the presence of the human papillomavirus virus (HPV), as well as other conditions like cervical cancer. Yale Medicine Pathology offers specialized expertise in the interpretation of Pap tests.

A Pap test is a routine collection of cells from a woman’s cervix, the lower end of the uterus that connects to the vagina.

According to Angelique W. Levi, MD, a Yale Medicine pathologist, the Pap test has evolved significantly over time. Today’s Pap test not only shows that a woman has or may develop cervical cancer, but it can also be used to test for a wide range of other diseases, including human papilloma virus (HPV) and other sexually transmitted diseases that have major implications for a woman’s health and longevity.

“There is a significant association between HPV infection and cervical cancer,” Dr. Levi says. “It’s the most common reason why atypical cells may develop into dysplastic lesions and ultimately, cervical cancer.”

It’s recommended that sexually active women receive a Pap smear every 1-3 years, depending on each woman’s risk profile, such as age, sexual history and HPV status. The procedure to collect cells from the cervix can be uncomfortable but not usually painful. Dr. Levi says that the samples are obtained during a pelvic exam through a tool that is like a small broom or brush. The specimen is then put into a tube containing a preservative liquid and sent to the pathology lab. There, it will be examined for abnormal cells that indicate a raised risk for cancer.

In the pathology lab, the cervical cells are put on a glass slide using automated machinery. A specific staining procedure, called the Pap stain, is applied. This makes it easier to distinguish cells at different stages of maturation, as well as abnormal cells from normal ones.

“We look at anywhere between 5,000 and 50,000 cells on a particular slide,” Dr. Levi says. “At Yale, the slides are screened not just by humans, but also by machines equipped with software that brings our attention to areas of particular concern.”

Areas where cells appear irregular are flagged by an automated computer-based screening system, and then re-screened manually by a team of highly trained cytotechnologists for in-depth analysis. If a specific type of abnormality is identified, it is graded according to specific criteria that will be used to create a treatment plan.

“We follow a series of steps and use a classification system that has been developed over the past decade to standardize grading of the abnormal cells,” Dr. Levi says.

Once the cells have been studied and classified, the pathologist creates a report for the gynecologist. 

Follow-up tests may include molecular testing to pinpoint the origins of abnormal cells. They may also include colposcopy, which involves a visual examination of the cervix and a small tissue sample for biopsy. If a lesion has been identified, the patient may need to undergo surgery for removal of cancerous or precancerous tissue. Many gynecology offices are equipped with the technology to do these additional diagnostic and therapeutic procedures, or they may be performed in an outpatient clinic.

At Yale Medicine, upon clinician request, specimens can be screened for 13 types of high-risk HPV strains, and may be further characterized by molecular testing for specific genotypes.

“We also perform molecular testing to identify different microorganisms which may cause vaginosis,” a group of common symptoms with many etiologies, ranging from bacterial to fungal infection, due to Gardnerella vaginalis and Candida species to organisms transmitted with intercourse such as herpes, trichomoniasis, chlamydia or gonorrhea, Dr. Levi says.

Yale Medicine has state-of-the-art equipment for cutting-edge molecular testing, Dr. Levi says. “We are often a beta site for new technology as it is being developed,” she says. Better equipment yields more accurate results. In addition to automated screening systems, “we have an invaluable team of 10 certified cytotechnologists who have on average a decade of screening experience,” Dr. Levi says.

The experienced team supports the intense quality control and quality assurance practices in the cytopathology laboratory at Yale Medicine, above and beyond national standards. “Our high standards play a large part in minimizing or eliminating interpretive errors," Dr. Levi says. "Many commercial and private laboratories cannot afford in this in the era of cost-cutting measures of healthcare delivery.” 

Yale Medicine’s team of pathologists have subspecialty training and board certification in cytopathology. This specialty of pathology focuses on the identification and diagnosis of disease at the cellular level. 

Additionally, Yale Medicine’s pathologists focus their clinical or basic science research in areas of special interest. Dr. Levi specializes in cervicovaginal cytopathology, the discipline around Pap tests.

“Here at Yale, all the people who are reviewing samples are of the same high caliber. We all hold ourselves to the same high standard,” Dr. Levi says.