Researchers in Japan have documented two instances of vaginal transmission of cancer from mother to child. Next-generation sequencing revealed that both children developed lung cancer from maternal uterine cervical tumors transferred during childbirth.

In Japan, next-generation sequencing (NGS) revealed two instances of vaginal transmission of cancer during birth: In both cases, children developed lung cancer from maternal uterine cervical tumors. The findings are intriguing, experts agree, but unlikely to change clinical care for pregnant women with cervical cancer in the United States.

Cancer transmission from mother to child is rare, occurring in one out of 500,000 mothers worldwide. To date, scientists have described 18 instances of maternal cancer transmission. However, these malignancies appeared to be transmitted via the placenta and involved tumor cells infiltrating multiple organs in the child.

“Theoretically, mother-to-infant transmission of tumor in the birth canal during vaginal delivery is also possible,” says senior author Takashi Kohno, PhD, of the National Cancer Center in Tokyo, Japan. Until now, however, “data on such mother-to-infant transmission were lacking.”

TOP-GEAR is a large-scale, prospective study in Japan that pairs NGS of tumors with information on responses and side effects during treatment. “The purpose of this project is to show the clinical utility of NGS-based tumor profiling in daily oncology,” explains lead author Ayumu Arakawa, MD, also of the National Cancer Center. While analyzing data from TOP-GEAR, the team uncovered two instances of pediatric lung cancer—in boys ages 2 and 6—linked to the mothers' uterine cervical tumors.

In each case, NGS established that the child's tumor lacked a Y chromosome—and shared somatic mutations, a human papillomavirus (HPV) genome, and single-nucleotide polymorphism alleles with the mother's tumor. Unlike previous cases of maternal cancer transmission, the malignancies were confined to the lungs. This, along with the pattern of tumor growth, suggested that the infants developed the malignancies after aspirating cancer-containing fluid during vaginal delivery.

“It was quite surprising that mothers' tumor cells can be delivered to the boys' lungs at birth,” Kohno says, noting that this phenomenon had not been previously documented. The team will continue to study these cases and gather more data on vaginal transmission of cancer to establish how often it occurs.

“This was really interesting because of the science that they did—looking at the tumors from mom and child to prove this point,” says Premal Thaker, MD, of Siteman Cancer Center in St. Louis, MO, who was not involved in the work. However, she notes that cesarean sections are standard for mothers with cervical cancer in the United States and many other countries, in part due to concerns about cancer transmission. “I'm not sure it's necessarily going to change how we practice because we've always thought of this theoretical risk,” she says.

Lois Ramondetta, MD, of The University of Texas MD Anderson Cancer Center in Houston, who was also not connected to the research, agrees. Cesarean sections, she says, are primarily done to avoid complications in mothers with cervical cancer, so the analysis provides “yet another reason not to deliver women with cervical cancer vaginally.”

The cases also reinforce the value of HPV vaccination in preventing cervical cancer, Ramondetta says, noting that the mothers and children all had HPV. Arakawa agrees, adding that neither mother had been vaccinated—which is unsurprising given that the “HPV vaccination rate is only 1% in Japan.”

The analysis also demonstrates the power of NGS—and the importance of compiling genomic data in large, shared databases. “I feel like we have a missed opportunity because of the siloed way we're doing molecular testing,” Ramondetta says. “Imagine how fast the world could learn things if we all had the same database.” –Catherine Caruso