- Design
- Retrospective immunohistochemistry and HPV ISH study
- Population
- 29 cervical neuroendocrine carcinomas; 10 pulmonary small cell carcinomas for comparison
- Primary outcome
- HPV status and p16, Rb, p53, cyclin D1 patterns
- Effect
- 96% HPV-positive; all HPV-positive with partial Rb loss vs complete loss in 9/10 lung
A Histopathology study profiled 29 uterine cervical neuroendocrine carcinomas with immunohistochemistry for p16, Rb, p53 and cyclin D1 and high-risk HPV mRNA in situ hybridisation, comparing them with 10 pulmonary small cell carcinomas. Most cervical tumours were small cell carcinomas combined with adenocarcinoma or squamous carcinoma.
Of 28 cervical tumours tested, 27 (96%) were HPV-positive. All HPV-positive tumours showed p16 overexpression, partial Rb loss, a wild-type p53 pattern and negative cyclin D1. The lung tumours were all HPV-negative and p16-positive, but nine of ten showed complete Rb loss and eight of ten had aberrant p53.
The point is diagnostic: p16 is positive in both, so it cannot by itself tell a cervical primary from a lung metastasis. The pattern of Rb loss — partial in HPV-driven cervical tumours, complete in lung — adds a discriminator, alongside HPV in situ hybridisation.
- p16 is positive in both cervical and pulmonary small cell carcinoma, so it does not establish site of origin.
- Partial Rb loss favours an HPV-associated cervical neuroendocrine carcinoma.
- Complete Rb loss with aberrant p53 favours a pulmonary small cell carcinoma.
- Confirm HPV status with high-risk HPV in situ hybridisation where site of origin is uncertain.
Why it matters
Telling a cervical primary from a lung metastasis changes staging and treatment, and p16 alone cannot do it.
Don't overread it
The comparison rests on 10 lung cases; the Rb pattern needs validation before it is used alone.
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