1. [Role of p16(INK4A) in detection of human papillomavirus DNA and stratification of cancer-specific mortality on the basis of long term follow-up data of 34 patients with invasive penile cancer].
- Author
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Bründl J, Neppl C, Hommer T, Otto W, Breyer J, Brookman-May S, Weber F, Burger M, May M, and Eichelberg C
- Subjects
- Aged, Carcinoma, Squamous Cell diagnosis, Carcinoma, Squamous Cell mortality, Carcinoma, Squamous Cell pathology, Human Papillomavirus DNA Tests, Humans, In Situ Hybridization, Male, Middle Aged, Neoplasm Invasiveness, Neoplasm Staging, Papillomaviridae isolation & purification, Papillomavirus Infections mortality, Papillomavirus Infections pathology, Penile Neoplasms mortality, Penile Neoplasms pathology, Penis pathology, Penis virology, Prognosis, Carcinoma, Squamous Cell genetics, Cyclin-Dependent Kinase Inhibitor p16 genetics, DNA, Viral genetics, Papillomaviridae genetics, Papillomavirus Infections diagnosis, Penile Neoplasms diagnosis
- Abstract
Background: Human papillomavirus (HPV) infection plays an important role in the pathogenesis of penile squamous cell carcinoma (PSCC) in about one third of the affected patients. Initial data indicate that HPV status could facilitate optimised risk stratification and individualised targeted therapy. The polymerase chain reaction (PCR) assay is the reference method for detection of HPV DNA. It is unclear if alternatives such as in situ hybridisation (ISH) or various surrogate markers (defined as immunohistochemical detection of p16INK4a, histological subtype, tumour invasion front, koilocytosis) are sufficient to determine HPV status METHODS: In this single centre study on 34 patients with PSCC, multiplex nested PCR and ISH were conducted for HPV detection and identification of HPV DNA genotypes. Various histological criteria and p16INK4a were determined by central review. The influence of different criteria on cancer-specific mortality (CSM) was investigated with the Cox proportional hazards models (FU: 92 mo.). Furthermore, the discriminative qualities of various tumour invasion patterns (i. e., pT-classification 7th vs. 8th ed.) for CSM prediction were compared., Results: Pursuant to PCR assay, HPV DNA was detected in 26 % of patients (n = 9). ISH and the examined histological criteria were of inadequate quality in the prediction of HPV status (p > ;0.3). Test parameters of p16INK4a were calculated as follows: sensitivity 66.7 %, specificity 84 %, positive predictive value 60 %, negative predictive value 87.5 %, overall agreement 79.4 % (Area-Under-Curve: 0.753, p = 0.026). None of the examined HPV criteria significantly influenced CSM. In comparison to the 7th pT-edition, the 8th version was superior in CSM prediction (c-indices 70.2 % vs. 72.9 %). In addition to penile corpora invasion, infiltration of the urethra had no independent predictive value. Regrouping of the corpora invasion patterns, as proposed by us, resulted in an increase in discriminative quality (c-index 77.9 %)., Conclusions: In contrast to ISH and the examined histological criteria, p16INK4a allows a reasonable prediction of HPV status. Neither HPV DNA nor its surrogate markers independently impacted CSM. As urethral tumour invasion does not independently influence CSM, the recent pT classification can be considered useful for prognosis., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)
- Published
- 2019
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