乌鸦传媒

Vaginal transmission of cervical cancer -- a phenomenon that has not been previously reported -- was detected in two pediatric patients, researchers in Japan reported.

Two boys whose mothers had undetected cervical cancer at delivery went on to develop lung cancer in early childhood, most likely resulting from mother-to-infant transmission of uterine cervical tumor cells, according to Ayumu Arakawa, MD, of the National Cancer Center in Tokyo, and colleagues.

Spontaneous regression of lesions in one child, as well as slow tumor growth in the other, suggested that there was an alloimmune response in the children, they stated in a brief report in the .

Additionally, immune checkpoint inhibitor therapy with nivolumab (Opdivo) was effective in shrinking tumors in one patient, possibly due to the presence of this alloimmune response, Arakawa's group noted.

"To our knowledge, this is the first report of vaginal transmission of cancer to infants," Arakawa told 乌鸦传媒 in an email. "It is also very important that nivolumab showed drastic efficacy to this type of tumor."

Melissa Frey, MD, an ob/gyn in the gynecologic oncology department at Weill Cornell Medicine in New York City, said that while passing malignancies from mother to baby is rare, this paper challenges how physicians think about transmission.

"I think what is most interesting about this study is that [transmission] is not thought to be hematogenous, which is the way we have previously conceptualized maternal-fetal transmission," Frey, who was not involved in this research, told 乌鸦传媒. She added that the findings have "tremendous implications for the way we think about delivery."

While mode of delivery in pregnant cervical cancer patients has previously centered on maternal implications, Frey said that "this paper asks us to think about the fetal implications in the setting of maternal cervical cancer."

Maternal transmission of cancer to offspring is extremely rare, occurring in around one in 500,000 mothers with cancer. There are 18 previously reported cases of mother-to-infant cancer transmission, all of which were presumably passed transplacentally. Due to the placental barrier and fetal alloimmune response, transplacental cancer transmission is rare, researchers noted.

Vaginal transmission, albeit rare, also has the potential to occur during vaginal birth. If an infant is exposed to tumor cells in the birth canal, they could potentially aspirate those cells into the lungs.

Arakawa's group detected these two cases of vaginal cancer transmission during routine next-generation sequencing of paired samples of tumor and normal tissues. The researchers found similar histological patterns in both mothers and their children, leading them to suspect uterine transmission. The analysis was a part of the TOP-GEAR trial, a prospective gene-profiling trial of patients with advanced cancer.

The first patient, a boy age 23 months, presented to the hospital with a cough that had persisted for 2 weeks. A CT scan showed several masses along the bronchi in both lungs, and a lung biopsy uncovered neuroendocrine carcinoma of the lung with focal glandular differentiation.

He was delivered vaginally at 39 weeks, after his mother previously tested negative for cervical cancer via Pap test 7 months before. The mother received a diagnosis for squamous cell carcinoma of the cervix 3 months after giving birth.

The child received frequent follow-up, but was not treated until he turned age 3 years. The researchers noticed some spontaneous regression of his tumors, but there was still several spread along the bronchi. After two chemotherapy regimens and further disease progression, physicians enrolled the patient in a clinical trial of nivolumab therapy. He did not inherit HLA class I alleles, a phenomenon that may have led to initial survival of maternal cancer cells, according to Arakawa and colleagues

He received four cycles of nivolumab at a dose of 3 mg per kg every 2 weeks, which resulted in a shrinkage of all lesions. After 14 cycles of nivolumab and lobectomy, researchers noted no evidence of disease recurrence.

The second patient, a boy age 6 years, presented to the hospital with chest pain. Researchers found a mass on the child's left lung, and he was diagnosed with mucinous adenocarcinoma. Before he was born, physicians detected a cervical polypoid tumor in the mother. However, as a cervical cytologic test was negative and the tumor appeared stable, the mother delivered the boy vaginally at 38 weeks.

After several cycles of chemotherapy and disease recurrence, he underwent total left pneumonectomy and, 15 months later, was free from disease. Both mothers died of their disease.

Arakawa and colleagues wrote that transmission was demonstrated by the fact that tumors in both pediatric patients lacked the Y chromosome, as well as shared somatic mutations, an HPV genome, and SNP alleles with tumors found in each of their mothers. Additionally, the metastases in both of these cases were localized in the respiratory region, whereas transplacental transmission may result in dispersed metastases throughout the brain, bones, liver, and soft tissues.

This mode of transmission is extremely rare, Arakawa said. But as these reports indicate that vaginal transmission may be possible when infants inhale tumor cells during birth, the researchers recommended that pregnant people with cervical cancer plan for a cesarean section birth.

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