Cells Most Vulnerable to HPV Are Identified

By NICHOLAS BAKALAR

Scientists have located the cells in the cervix that give rise to cancer when attacked by the human papillomavirus, a discovery that may lead to new methods of preventing and treating the disease.

Even though the virus pervades the entire genital tract, HPV infection causes precancerous and cancerous lesions in just one part of the cervix, called the ectoendocervical squamocolumnar junction, or SC junction. Now researchers have found that cervical cancers are linked to a small population of distinct cells in that region.

The researchers began by examining cells from the SC junction in the cervices of patients not infected with HPV. Among the samples they found some cells that under a microscope looked different from those in adjacent areas.

Then they looked at the cells of precancerous and cancerous lesions, comparing the form and genetic makeup of those cells with the SC junction cells. They matched, and so the scientists believe that they have found the cells in which most, if not all, cervical cancers arise.

Dr. Christopher P. Crum, the senior author, said that the discovery follows findings in a 2011 study led by Frank McKeon and Wa Xian at Harvard, who found the same cells in Barrett esophagus, a precursor of esophageal cancers. (Research has linked these cancers, too, to HPV infection.)

The new study was published online June 11 in the journal Proceedings of the National Academy of Sciences.

“These markers could be used to more clearly define which precancers need to be treated versus those that need to be followed, so you don’t go doing surgery on women who have innocuous infections,” said Dr. Crum, a professor of pathology at Harvard.

Dr. Mark H. Einstein, a gynecologic oncologist at Montefiore Medical Center in the Bronx who was not involved in the study, agreed that this could be an important clinical application of the finding.

“The procedures that treat the precancerous cells can lead to preterm birth in some women, so we want to avoid them if possible,” he said. “Sometimes doing less is more.”

Although the researchers say they cannot rule out that SC junction cells might develop spontaneously, they are almost certain that they appear during fetal development and exist in all women, regardless of age.

Markers of SC junction cells are always present in high-grade precancerous and cancerous lesions, and they are absent in most low-grade lesions. In this study, their presence accurately predicted the precancerous lesions most likely to become malignant, those infected by HPV Type 16.

The discovery might also lead to prophylactic treatment, at least in areas of the world where routine care like cervical cancer screening is unavailable.

“Given how small the area is that these cells occupy,” Dr. Crum said, “they might very easily be removed or ablated by some means which could be a cost-effective way of preventing cervical cancer. There are people who claim anecdotally that this would work, and it’s a concept worth thinking about.” The cells do not regenerate after they are cut away.

Clinical application of the discovery could be very close, Dr. Einstein said.

“This is something that could probably be adopted by clinicians and pathologists pretty soon,” he said. “These investigators have actually identified the type of cells which can then be used to target new methods of testing, treatment and screening. It’s fantastic.”