Maternal cancer transmission via tumour-contaminated vaginal fluid aspiration

February 2021 Clinical Practice Tobias Rawson

Transmission of maternal cancers to their child is extremely rare, occurring in approximately 0.2% of mothers with active cancer. Recently, investigators of the TOP GEAR trial reported on two suspected cases of direct vaginal transmission of cervical cancer cells to the lungs, likely due to the aspiration of tumour-contaminated vaginal fluid during delivery.

Expert opinion

‘One in a thousand live births occur in a mother with cancer. Direct mother to infant transmission of cancer is nevertheless very rare (1 in 500K) and infants are effectively protected by the placental barrier and the fetal alloimmune response. As a result, the cancer transmission risk is very low, occurring in only 0.2% of mothers with active cancer. Usually, these infants have disseminated disease due to hematogenic transmission. The paper discussed here describes the first two cases of direct vaginal transmission of cervical cancer cells to the lungs, likely due to the aspiration of tumour-contaminated vaginal fluid during delivery. Based on these observations, women delivering with cervical cancer should (if already not for other reasons), deliver with a cesarean section to avoid mother-to-child cancer transmission.’

Introduction

Transmission of maternal cancers to offspring is extremely rare, occurring in approximately 1 infant per 500,000 mothers with cancer. The most likely route of transmission is haematogenously via the placenta, or in the birth canal during a vaginal delivery. Recently, 2 suspected cases paediatric lung cancers that probably developed through mother-to-infant transmission of cervical carcinoma have been reported by the TOP GEAR trial investigators during routine oncogenic genome profiling.

Patient 1

Following a 2-week history of productive cough, a 23-month-old boy was found to have a neuroendocrine carcinoma of the lung. The mother was not vaccinated with the HPV vaccine and had a negative cervical cytological test 7 months before transvaginal delivery. However, 3 months post-delivery she was diagnosed with cervical squamous-cell carcinoma and underwent hysterectomy. Histological examination of the hysterectomy revealed a poorly differentiated squamous-cell carcinoma with focal neuroendocrine differentiation with an adenocarcinoma component. NGS of both mother and child tumours found the same pathogenic KRAS and TP53 mutations in addition to 47 exonic single-nucleotide polymorphisms (SNPs) that were not included in the child’s germline. Fluorescent in situ hybridisation (FISH) revelaed that the boy’s tumour lacked the Y chromosome and whole-exome sequencing identified a further 20 somatic mutations detected in both mother and child tumour samples. Non-inherited HLA class I alleles were also lost in both tumour samples. Both tumours were PD-1/PD-L1 negative and were positive for HPV type 18.

Patient 2

A 6-year-old boy received a diagnosis of inoperable mucinous adenocarcinoma, following a history of left-sided chest pain. A cervical polypoid tumour was detected in the child’s mother, although a cervical cytological analysis turned out negative and the child was delivered transvaginally. A biopsy of the cervical lesion post-delivery revealed an adenocarcinoma. NGS of the child’s lung tumour and the mother’s cervical tumour revealed the same KRAS and STK11 mutations, plus 38 exonic SNPs that were not inherited in the child’s germline. Also in this case a FISH analysis revealed that the child’s tumour lacked a Y chromosome and whole-exome sequencing detected an additional 14 somatic mutations that were present in both tumours. Loss of HLA class I alleles were not detected in either tumour, and both were positive for HPV type 16.

Reference:

Arakawa A, Vaginal Transmission of Cancer from Mothers with Cervical Cancer to Infants. N Engl J Med. 2021 Jan 7; 384(1):42-50.

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