Correlation of p16 immunohistochemistry with clinical and epidemiological features in oropharyngeal squamous-cell carcinoma

Background Oropharyngeal cancer is an important public health problem. The aim of our study was to correlatep16 immunohistochemistry in oropharynx squamous cell carcinomas(OPSCC) with clinical and epidemiological features. Material and methods We conducted across-sectional study on patients with OPSCC treated at a single institution from 2014 to 2019. Epidemiological and clinical-pathological data were collected from medical records and a questionnaire was applied to determine alcohol consumption, smoking, and sexual behavior. The HPV status was determined by p16 immunohistochemistry. Results A total of 252 patients participated in the study, of these 221 (87.7%) were male. There were 81 (32.14%) p16 positive cases and 171 (67.85%) p16 negative cases. The p16positive group was significantly associated with younger patients (50–59 years), higher education level, lower clinical stage and patients who never drank or smoked. Through univariate logistic regression, we observed that female sex (OR, 3.47; 95% CI, 1.60–7.51) and higher education level (OR, 9.39; 95% CI, 2, 81–31,38) were significantly more likely to be p16 positive. Early clinical stage (AJCC8ed) was more associated with p16 positivity both in univariate (OR, 0.14; 95% CI, 0.07–0.26, p<0.001) and multivariate analysis (OR, 0.18; 95% CI, 0.06–0.49, p = 0.001). Conclusion This study showed that drinkers and current smokers were less likely to be p16+. Female sex, higher education level and younger age at diagnosis were associated with a higher probability of being p16+. Additionally, there was a higher proportion of patients with early clinical stage (I or II) in the p16 positive group when compared to the p16 negative group.

Tumor-Associated Trypsin Inhibitor (TATI) as a Biomarker of Poor Prognosis in Oropharyngeal Squamous Cell Carcinoma Irrespective of HPV Status

Background: We studied the role of tumor-associated trypsin inhibitor (TATI) in serum and in tumor tissues among human papillomavirus (HPV)-positive and HPV-negative OPSCC patients. Materials and methods: The study cohort included 90 OPSCC patients treated at the Helsinki University Hospital (HUS), Helsinki, Finland, in 2012–2016. TATI serum concentrations (S-TATIs) were determined by an immunofluorometric assay. Immunostaining was used to assess tissue expression. HPV status was determined with a combination of p16 immunohistochemistry and HPV DNA PCR genotyping. The survival endpoints were overall survival (OS) and disease-specific survival (DSS). Results: A significant correlation was found between S-TATI positivity and poor OS (p < 0.001) and DSS (p = 0.04) in all patients. In HPV-negative cases, S-TATI positivity was linked to poor OS (p = 0.01) and DSS (p = 0.05). In HPV-positive disease, S-TATI positivity correlated with poor DSS (p = 0.01). S-TATI positivity was strongly associated with HPV negativity. TATI serum was negatively linked to a lower cancer stage. TATI expression in peritumoral lymphocytes was associated with favorable OS (p < 0.025) and HPV positivity. TATI expression in tumor and in peritumoral lymphocytes correlated with lower cancer stages. Conclusion: Our results suggest that S-TATI positivity may be a biomarker of poor prognosis in both HPV-positive and HPV-negative OPSCC.

Human Papillomavirus Testing in Head and Neck Squamous Cell Carcinoma: Impact of the 2018 College of American Pathologists Guideline Among Referral Cases at a Large Academic Institution

Context.— Given the growing clinical significance of human papillomavirus status in oropharyngeal squamous cell carcinoma, the College of American Pathologists established a set of evidence-based recommendations for high-risk human papillomavirus testing. Objective.— To evaluate the impact of the recommendations on human papillomavirus ancillary test ordering habits by comparing compliance before and after the guideline was published. Design.— We retrospectively reviewed head and neck squamous cell carcinoma biopsy or resection specimens from outside institutions during a 2.5-year period around guideline publication for whether or not human papillomavirus testing was performed in accordance with the guideline. Results.— Human papillomavirus testing deviated from the guideline in 45 of 107 cases (42.1%) before and 93 of 258 cases (36.0%) after their publication (P = .29). This included 6 of 26 cases of oropharyngeal squamous cell carcinoma (23.1%) before and 5 of 55 cases (9.1%) after (P = .16), with 5 of 5 (100.0%) after due to not performing p16 immunohistochemistry. This also included 30 of 68 cases of nonoropharyngeal carcinoma (44.1%) before and 69 of 163 (42.3%) after the guideline was published (P = .88), with 29 of 30 (96.7%) before and 67 of 69 (97.1%) after due to unnecessary use of p16 immunohistochemistry. Nodal metastasis testing deviated in 9 of 13 cases (69.2%) before and 19 of 40 cases (47.5%) after (P = .21) with marked variability in testing, including 3 of 9 (33.3%) before and 8 of 19 (42.1%) after, for not confirming certain p16 immunohistochemistry–positive tumors with human papillomavirus–specific testing. Conclusions.— Pathologists continue to deviate from the testing guideline significantly in everyday practice. Further education and discussion about the appropriate handling of head and neck cancer specimens may be needed.

Classifying Anal Intraepithelial Neoplasia 2 Based on LAST Recommendations

Objectives: The Lower Anogenital Squamous Terminology (LAST) recommendations classify human papillomavirus–associated squamous lesions into low- and high-grade squamous intraepithelial lesions (LSILs/HSILs). Our study aimed to assess interobserver agreement among 6 experienced pathologists in assigning 40 anal lesions previously diagnosed as anal intraepithelial neoplasia 2 (AIN 2) to either HSIL or non-HSIL categories. Methods: Agreement based on photomicrographs of H&E alone or H&E plus p16 immunohistochemistry was calculated using κ coefficients. Results: Agreement was fair based on H&E alone (κ = 0.42; 95% confidence interval [CI], 0.34-0.52). Adding p16 improved agreement to moderate (κ = 0.55; 95% CI, 0.54-0.62). On final diagnosis, 21 cases (53%) had unanimous diagnoses, and 19 (47%) were divided. When designating p16 results as positive or negative, agreement was excellent (κ = 0.92; 95% CI, 0.83-0.95). Among variables (staining location, extent, and intensity), staining of the basal/parabasal layers was a consistent feature in cases with consensus for positive results (20/20). Of the 67 H&E diagnoses with conflicting p16 results, participants modified 32 (48%), downgrading 23 HSILs and upgrading 9 non-HSILs. Conclusions: Although p16 increased interobserver agreement, disagreement remained considerable regarding intermediate lesions. p16 expression, particularly if negative, can reduce unwarranted HSIL diagnoses and unnecessary treatment.