Design: Retrospective immunohistochemical and in situ hybridisation case series
Population: 29 cervical neuroendocrine carcinomas and 10 lung small cell carcinomas
Primary outcome: HPV status and p16, Rb, p53 and cyclin D1 patterns
Effect: 27/28 cervical tumours HPV positive, all with partial Rb loss; 9/10 lung tumours with complete Rb loss

A series in Histopathology (30 September 2026) studied 29 uterine cervical neuroendocrine carcinomas with p16, Rb, p53 and cyclin D1 immunohistochemistry and high-risk HPV mRNA in situ hybridisation, and compared them with 10 lung small cell carcinomas.

Most cervical tumours were small cell carcinomas mixed with adenocarcinoma or squamous carcinoma. Of 28 tested for HPV, 27 were positive. Every HPV-positive tumour showed diffuse p16, partial loss of Rb, wild-type p53 and no cyclin D1. Lung small cell carcinomas were HPV negative, p16 positive, usually showed complete Rb loss (9 of 10), and often had aberrant p53.

The numbers are small. The finding is still useful for the question pathologists actually face: a small cell carcinoma in the cervix, or a metastasis from one. p16 cannot separate the two because both stain. The pattern of Rb loss, alongside HPV in situ hybridisation, may.

Do not use p16 alone to separate cervical from lung small cell carcinoma; both are p16 positive.
Consider Rb immunohistochemistry: partial loss favoured cervical, complete loss favoured lung in this series.
Use HPV in situ hybridisation where available to support cervical origin.
Look for an associated adenocarcinoma or squamous component, common in cervical cases.

Why it matters

It gives a practical way to resolve a site-of-origin question where the usual surrogate, p16, is uninformative.

The statistics, in plain English

With 27 HPV-positive cervical tumours and 10 lung tumours, the patterns are striking but the series is too small to give reliable sensitivity and specificity for Rb as a test.