HPV18-Positive Cervical Large Cell Neuroendocrine Carcinoma With Rapid Progression Despite Pembrolizumab Combined With Chemotherapy: A Case Report With Immunogenomic Insights.

HPV18-positive cervical large cell neuroendocrine carcinoma (LCNEC) is exceptionally rare. We report a 40-years-old woman with FIGO 2018 stage IVB LCNEC who progressed rapidly despite paclitaxel-carboplatin-bevacizumab plus pembrolizumab, followed by concurrent chemoradiotherapy and later cytotoxic regimens. Biopsy showed chromogranin A and synaptophysin positivity, diffuse p16, and Ki-67%~80%. Comprehensive profiling revealed very low tumor mutational burden (TMB, 1.21/Mb), microsatellite stability, no homologous recombination deficiency, and minimal PD-L1 (~1%), consistent with a poorly immunogenic tumor microenvironment (TME). This profile may explain the limited effect of immune checkpoint inhibition in this histology. The case suggests that HPV or p16 positivity alone did not predict clinical benefit from pembrolizumab-based therapy in advanced cervical LCNEC, and supports careful biological assessment before treatment selection. These observations provide practical guidance for clinicians and support evaluation of alternative or investigational strategies for this aggressive tumor.