HPV 16 and/or 18 were detected in 156 (80%) tumors. p16 was positive in 186 (96%) carcinomas, but eight tumors (4%) were negative for p16 (seven squamous cell carcinomas, one adenocarcinoma); 5/8 caused by HPV 16 and/or 18.
Cyfra21-1 assay showed significant differences between tumors of different sites with prominent elevation being found in oropharyngeal carcinomas and between patients with p16 positive and p16 negative HNSCC (p=0.0242), being elevated in p16 positive tumors.
Results The major recommendations include (1) testing newly diagnosed oropharyngeal squamous cell carcinoma patients for high-risk HPV, either from the primary tumor or from cervical nodal metastases, using p16 immunohistochemistry with a 70% nuclear and cytoplasmic staining cutoff, and (2) not routinely testing nonsquamous oropharyngeal carcinomas or nonoropharyngeal carcinomas for HPV.
Gross tumor volume (GTV) from the PET/CT radiation treatment planning CT scan, maximal Standard Uptake Value (SUVmax) of fludeoxyglucose (FDG) and clinical information were included in the model building using Cox proportional hazards models, stratified for p16 status in oropharyngeal carcinomas.
Diffuse p16 staining in ≥75% of tumour cells was noted in all HPV-related carcinomas with adenoid cystic-like features but in only one AdCC (100% versus 7%, P < 0.01).
In ovarian epithelial carcinogenesis, p16 and p53 show higher immunohistochemical staining frequencies in malignant tumors and are associated with poor prognoses. p14 was only analyzed in carcinomas, with conflicting results.
The scraped cell material from FNA smears and corresponding surgical specimens were analyzed for HPV DNA by PCR. p16 immunohistochemistry was performed on surgical specimens from the carcinomas.
There were 11 low-grade tumors, 5 frankly invasive carcinomas, and 1 with histologic features that were intermediate between the former 2 categories. p16 immunostain was negative or showed patchy cytoplasmic staining in the low-grade tumors and was strongly and diffusely positive in the invasive carcinomas.
We conclude that: (1) BAP1 immunohistochemistry is relatively insensitive in the context of sarcomatous and desmoplastic mesotheliomas, but as a matter of time and cost efficiency may nonetheless be a useful first approach to the problem; (2) deletion of p16 by FISH is considerably more sensitive, but there remain a proportion of cases in which p16 is not deleted; (3) a small improvement in sensitivity can be achieved by using both markers; (4) in the context of a spindle cell malignant tumor in the pleura or peritoneum, which morphologically might be a metastatic sarcomatoid carcinoma or a mesothelioma, the finding of BAP1 loss favors mesothelioma, but p16 FISH cannot be used to separate sarcomatous mesotheliomas from sarcomatoid carcinomas.
We further examined the presence of human papillomavirus (HPV) DNA and p16 expression to probe the relationship between GNAS mutations and HPV infection in LEGHs and carcinomas.
HPV genotyping polymerase chain reaction (high-risk subtypes 16, 18, 31, 33, 45, 52, and 58) and immunohistochemical expression of p16 were analyzed by using paraffin-embedded tumor biopsies from 143 anal carcinomas.
The surgical pathology archives of The Johns Hopkins Hospital were searched for all carcinomas arising in the sinonasal tract from 1995 to 2011, and tissue microarrays were constructed. p16 immunohistochemical analysis and DNA in situ hybridization for high-risk types of HPV were performed.
Importantly all carcinomas associated with HPV6/11 globally showed verruco-papillary, well-differentiated, squamous, or transitional histology without p16 expression.
By the E6/E7 mRNA method, HPV was detected in 49 of 282 (17%) HNSCCs including 43 of 77 (56%) carcinomas from the oropharynx, 2 of 3 (67%) metastatic HNSCCs of an unknown primary site, 2 of 7 (29%) carcinomas from the sinonasal tract, and 2 of 195 (1%) carcinomas from other head and neck sites. p16 expression was strongly associated with the presence of HPV E6/E7 mRNA: 46 of 49 HPV-positive tumors exhibited p16 expression, whereas only 22 of 233 HPV-negative tumors were p16 positive (94% vs. 9%, P<0.0001).
Archival formalin-fixed high-grade penile intraepithelial neoplasias, differentiated penile intraepithelial neoplasias, and invasive carcinomas from a single pathology institution in a low-incidence area for penile cancer were analyzed for 28 HPV low-risk and HPV high-risk genotypes, p16 overexpression, presence of peritumoral lichen sclerosus, lichen planus, precursor lesions, and monoclonal rearrangement of the T-cell receptor γ locus.
With regard to methylation status, P16 and P14 showed significantly higher methylation frequencies in JCV-positive gastric carcinomas than in JCV-negative cases (P=0.007 and P=0.003, respectively).
Aberrant methylation of the p16 gene was detected in 17 out of the 49 (34%) primary gastric carcinomas, suggesting that the aberrant methylation of p16 is frequently observed in gastric carcinomas.