We found a p16 high expression rate of 86.7% in HPV DNA (+) patients in our specimens. Statistical power was lost because of p16 high expression (77.8%) also in HPV DNA (-) patients ( Table 1 ). Smeets et al. [ 14] reported that only 50% of the similar specimens were PCR (+) in formalin-fixed paraffin-embedded tissue.
Diffuse p16 immunostaining pattern is the hallmark of HSIL because it correlates 100% with CIN2 and CIN3 lesions between initial biopsy and LEEP specimens, regardless of the HPV status. The negative predictive value for p16 immunoreactivity to predict cervical lesions less than high grade is almost 100% in our study.
P16 immunostaining can be both positive and negative. P16 or INK4A immunostain is a strong indicator. It is used for high-risk-HPV associated dysplasias and oropharyngeal carcinomas. However, it is sometimes unreliable to predict low-risk-HPV-infection in neck and head papillomas and laryngeal dysplasias.
Mean age of the patients involved in the study was 48.9 years. Most of the patients presented at stage T2 with a high mean ki67 index i.e. 46.9%. 42.7% of cases had nodal metastasis. Seventy-one percent (98 cases) of cases showed positive p16 expression, whereas 24.8% (34 cases) were negative and 3.6% (5 cases) showed focal positive p16
The pattern of p16 immunoreactivity of the HPV-positive tonsillar carcinomas was similar to that observed in HPV-positive cervical carcinomas, which were used as a positive control (Figure 1D) . Only in the HPV-positive cases did the dysplastic peritonsillar epithelium show marked p16 expression and the border between dysplastic and normal
According to the 2006 American Society for Colposcopy and Cervical Pathology guidelines, positive CIN2 p16 in women over the age of 25 should be managed with excisional treatment. However, excisional treatment is associated with physical, psychological and obstetric morbidity and can have a negative impact on sexual function. In our study we sought to identify a clear management strategy
This means that between 3 and 20 cells in every 100 cells (3% and 20%) are dividing. This is a grade 2 NET (WD NET G2). Ki-67 index higher than 20%. A Ki-67 index of more than 20% means that more than 2 in every 10 cells (20%) are dividing. This is either a grade 3 NET (WD NET G3) or a neuroendocrine carcinoma (PD NEC G3). Treatment
While most p16 results are distinctly positive or negative, certain ones are ambiguous: they meet some but not all requirements for the "block-positive" pattern. It is unclear whether ambiguous p16 immunoreactivity indicates oncogenic HPV infection or risk of progression.
Testing positive for HPV 16 or 18 doesn't mean you'll develop cervical cancer, but it does mean that any dysplasia found in a Pap test carries a higher risk of becoming a cancer.
The p16 gene belongs to INK4 family of genes and is made up of four members: p16 INK4A , p15 INK4B , p18 INK4C and p19 INK4D , all of which share biological properties, namely, inhibition of cell growth and tumour suppression. After p53 , p16 is the second most common tumour suppressor gene. It has been regarded as the familial melanoma gene. Immunohistochemistry for p16 has a well-defined
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