Pap Test May Detect Ovarian and Endometrial Cancers

Researcher, Luis Diaz, MD, from

Johns Hopkins Kimmel Cancer Center

New research has found that Papanicolaou (Pap) smear tests that collect DNA in addition to providing a routine cytologic evaluation may be able to identify mutations associated with ovarian and endometrial cancers, suggesting that the routine screening method might eventually provide an inexpensive and relatively accurate method of identifying patients with these difficult-to-treat tumors.

While the research is early and comes with many caveats, the authors of the study suggest that it should prompt more thorough studies to assess the accuracy of this method of screening for ovarian and endometrial cancers. The research was published in the journal Science Translational Medicine.

Since the advent of Pap tests—in which cells from the cervix are collected and examined for evidence of cancer—the incidence and mortality of cervical cancer in patients who receive the test has been reduced by more than 75%, according to the authors. However, more than 69,000 women in the United States were estimated to be diagnosed with endometrial and ovarian cancers in 2012, and the mortality rates have not substantially decreased over time.

The authors posited that a Pap test may be able to detect ovarian and endometrial cancers, since cells shed from the ovaries and endometrium occasionally end up in Pap smears. Using genome sequencing, researchers attempted to distinguish normal cellular DNA from cancerous cellular DNA. To do this, the researchers used whole-exome sequencing data from 22 endometrial cancers and previously published data on other tumor types to determine a panel to search for commonly mutated genes in ovarian and endometrial cancers. This allowed the researchers to develop a test called PapGene to look for the 12 most frequently mutated genes in both types of cancer.

Researchers used this panel on tumors from 46 cancer patients (24 endometrial and 22 ovarian) for whom Pap specimens were available. Since the tumors were known, the researchers used a sensitive massively parallel sequencing method to identify the same mutations in the Pap test specimens. The researchers were able to find the same mutations in 100% of the endometrial cancers (24 of 24 samples) and 41% of ovarian cancers (9 of 22 samples).

“Our genomic sequencing approach may offer the potential to detect these cancer cells in a scalable and cost effective way,” said Luis Diaz, MD, associate professor of oncology at Johns Hopkins Kimmel Cancer Center and director of the Swim Across America Laboratory, a volunteer-sponsored organization that raises funds for cancer research, and lead researcher of the study, in a statement.

The researchers noted that one of the most important findings of the study is that there are enough cells from endometrial and ovarian cancers that are present in the cervix that can be identified through genetic screening.

However, the researchers noted a number of important limitations to this study. For example, only 41% of ovarian cancers were detected in the Pap test, despite the fact that mutations in the tumors were already known. The authors suggest that modifications to improve the technical sensitivity of their PapGene test may be required to find more mutations or detect the mutations at lower fractions. Additionally, the existing method of conducting Pap tests involves using a brush to collect cells from the ectocervix. This method involves only minimal penetration of the endocervical canal, so other methods might be investigated to obtain a highly enriched sample of cells to come from the endometrium and ovary.

Because Pap tests are frequently used and relatively inexpensive to perform, the authors suggest that the method developed for this study—even with its modifications—could be used in a large scale.

“PapGene testing has the capacity to increase the use of conventional cytology screening through the unambiguous detection of DNA from endometrial and ovarian carcinomas, and lays the foundation for a new generation of screening tests,” the authors wrote.

Kinde I, Bettegowda C, Wang Y, et al. Evaluation of DNA from the Papnicolaou test to detect ovarian and endometrial cancers. Sci Transl Med. 2013;5(167):167ra4.