The cribriform morphology impairs Gleason 7 prostate cancer lesion detection on multiparametric magnetic resonance imaging.

BACKGROUND: Prostate multiparametric magnetic resonance imaging (mpMRI) is a useful tool for the detection of tumor lesions however, some clinically significant lesions are still missed. We determined whether the cribriform pattern has an effect on lesion detection in mpMRI. METHODS: We reviewed the single-institution database of the patients who underwent mpMRI before radical prostatectomy. We included the patients only with the Gleason 7 final pathology of open radical prostatectomy with curative intent between 2016 and 2021. Prostatectomy mappings according to the 16-sector map and cribriform patterns were re-evaluated by two genitourinary pathologists. Prostate mpMRIs were read by two genitourinary radiologists. If the index and nonindex lesions in pathology mapping were matched with mpMRI as Prostate Imaging Reporting and Data System-3 or higher, it was defined as detectable. We compared the detection rates of lesions with and without cribriform morphology. In regression analysis, we also assessed the factors affecting the detectability of prostate cancer lesions. RESULTS: A total of 120 patients and 157 lesions were included in our study. While 52 of 83 cribriform pattern positive lesions could be detected in mpMRI, 59 of 74 cribriform pattern negative lesions could be detected (62.7% vs. 79.7%, respectively, p = 0.019). The lesions were also distributed homogeneously according to diameters and analyzed separately. All lesions between 21 and 30 mm with the negative cribriform pattern were detected on mpMRI. However, only 77.8% of cribriform pattern positive lesions between 21 and 30 mm could be detected (p = 0.034). The Higher D'Amico risk group and the absence of cribriform morphology were independent predictors for the lesion detection on mpMRI. CONCLUSION: The presence of cribriform pattern in Gleason 7 prostate cancer lesions decreases the lesion detection rate of mpMRI.

Comparison of 68Ga-PSMA PET/CT and mp-MRI in regard to local staging for prostate cancer with histopathological results: A retrospective study.

BACKGROUND: Imaging modalities are used to diagnose and clinical grading of clinically significant prostate cancer. In this study, 68Ga-PSMA PET/CT (PSMA) and multiparametric prostate MRI (mp-MRI) were compared in regard to locating intraprostatic tumor and locoregional staging. METHODS: After ethics committee approval, a total of 49 patients with prostate cancer who had mp-MRI and PSMA before radical prostatectomy were included. Preoperative and postoperative PSA, transrectal ultrasound-guided prostate biopsy (TRUS-Bx) ISUP grade, radical prostatectomy ISUP grade, body mass index (BMI), TRUS prostate volume, mp-MRI tumor mapping, PSMAtumor mapping, pathologic tumor mapping, extraprostatic extension (EPE), seminal vesicle invasion (SVI), lymph node invasion (LNI), and bladder neck invasion (BNI)were retrospectively evaluated. Index tumor was located by uroradiologist, nuclear medicine specialist, and uropathologist on a 12-sector prostate pathology map and compared with each other in terms of accuracy and locoregional clinical staging. RESULTS: Mean age of the patients was 66.18 ± 6.67 years and the mean of preoperative PSA results was 21.11 ± 32.56 ng/ml. Nearly half of the patients' (44.9%) pathology was reported as ISUP grade 4 and 5% and 18.4% of patients were surgical margin positive. According to the pathological findings, 362 out of 588 sectors were tumor-positive, 174 out of 362 sectors were tumor-positive in mp-MRI, and 175 out of 362 sectors were tumor-positive in PSMA. Both PSMA and mp-MRI were comparable (p = 0.823) and accurate to detect the location of the intraprostatic index tumor (AUC = 0.66 vs. 0.69 respectively, p = 0.82). The sensitivity and the specificity of the PSMA and mp-MRI for localizing intraprostatic index tumors were 42.5% versus 49.5% and 90.7% versus 88.6% respectively. mp-MRI was more accurate than PSMA in terms of EPE (AUC = 0.8 vs. AUC = 0.57 respectively, p = 0.027) and both methods were comparable in terms of SVI (AUC = 0.75 vs. AUC = 0.75, p = 0.886) and BNI (AUC = 0.51 vs. AUC = 0.59, p = 0.597). PSMA and mp-MRI were comparable in terms of LNI (AUC = 0.76 vs. AUC = 0.64, p = 0.39). CONCLUSION: mp-MRI should be considered for its high accuracy in the diagnosis of EPE, especially before decision-making for nerve-sparing surgery in high-risk patients. Both imaging modalities were accurate for localizing intraprostatic index tumor. PSMA is accurate for detecting LNI.

The Correlation of Histopathologic Parameters With Mismatch Repair Protein-deficient Subgroups and MLH1 Methylation in Endometrial Carcinomas.

There are limited data regarding the correlation of clinical and pathologic parameters with mismatch repair (MMR) protein-deficient subgroups and methylation status. In this study, we analyzed the status of MMR proteins in resection specimens of 198 consecutive endometrial carcinomas and the methylation status in tumors with MLH1 and PMS2 deficiency. We, therefore, assessed the correlation of clinical and pathologic parameters with MMR protein-deficient subgroups. Univariate analysis revealed that deeper myometrial invasion and the presence of tumor-associated lymphocytes were more frequently observed in tumors with MMR protein deficiency ( P =0.023 and 0.001, respectively). The multivariate logistic regression analysis revealed that only the presence of tumor-associated lymphocytes was significantly associated with MMR protein deficiency ( P =0.002, odds ratio=2.674, 95% confidence interval=1.418-5.045). We also compared MLH1 and PMS2 deficiency with other protein deficiency regarding clinical and pathologic parameters. Furthermore, we compared MLH1 methylated tumors with MMR protein-deficient nonmethylated tumors regarding clinical and pathologic parameters. MLH1 was methylated in 51 of 54 tumors with MLH1 and PMS2 deficiency. In univariate analysis, a larger tumor size was significantly associated with MLH1 and PMS2 deficiency and with MLH1 methylation ( P =0.004 and 0.005, respectively). The multivariate logistic regression analysis revealed that a larger tumor size was significantly associated with MLH1 and PMS2 deficiency and MLH1 methylation ( P =0.002, odds ratio=14.222, 95% confidence interval=2.560-79.026, P =0.008, odds ratio=22.222, 95% confidence interval=2.220-222.395, respectively). Our results showed a slightly higher rate of MLH1 and PMS2 deficiency (34.3%) than in previous studies. This may likely be due to ethnic differences in frequency of various mutations.

The association between PI3K, JAK/STAT pathways with the PDL-1 expression in prostate cancer.

Programmed cell death protein-1/programmed death-ligand-1 (PD-1/PDL-1) signalling pathway has gained attention in prostate cancer. The relationship between pSTAT-1, pSTAT-3 expressions and PTEN loss with PDL-1 expression was assessed and the effects of the pathways on prostate cancer prognosis were evaluated. Patients who underwent radical prostatectomy between 2011 and 2017 were included in our study. Prostatectomy materials were evaluated using immunohistochemical staining of pSTAT-1, pSTAT-3, PTEN, and PDL-1. The relationship between PDL-1 and pSTAT-1, pSTAT-3 expressions and PTEN loss was evaluated. Additionally, factors affecting biochemical recurrence-free survival and clinical progression-free survival were analysed. Within100 patients, 9 of 11 patients with PDL-1 expression also had intermediate-high pSTAT-1 staining intensity, and those with PDL-1 expression had higher pSTAT-1 staining intensity than those without (81.9% vs. 56.2%, p = 0.014). In univariate analysis, pSTAT-1, pSTAT-3 and PDL-1 expressions had significant impact on biochemical recurrence-free and clinical progression-free survival. In multivariate analysis, pSTAT-1 staining intensity with radical prostatectomy ISUP grade in terms of biochemical recurrence-free survival and the pSTAT-1 H-score with radical prostatectomy ISUP grade in terms of clinical progression-free survival were independent risk factors. Moderate-high expression of pSTAT-1 was closely associated with PDL-1 expression, and pSTAT-1 was also a predictor of biochemical recurrence and clinical progression.

Germline pathogenic variant spectrum in 25 cancer susceptibility genes in Turkish breast and colorectal cancer patients and elderly controls.

Inherited pathogenic variants account for 5% to 10% of all breast cancer (BC) and colorectal cancer (CRC) cases. Here, we sought to profile the pathogenic variants in 25 cancer susceptibility genes in Turkish population. Germline pathogenic variants were screened in 732 BC patients, 189 CRC patients and 490 cancer-free elderly controls, using next-generation sequencing-based multigene panel testing and multiplex ligation-dependent probe amplification testing. Pathogenic variants were detected in 17.2% of high-risk BC patients and 26.4% of high-risk CRC patients. More than 95% of these variants were clinically actionable. BRCA1/2 and mismatch repair genes (MLH1, MSH2 and MSH6) accounted for two-thirds of all pathogenic variants detected in high-risk BC and CRC patients, respectively. Pathogenic variants in PALB2, CHEK2, ATM and TP53 were also prevalent in high-risk BC patients (4.5%). BRCA1 exons 17-18 deletion and CHEK2 c.592+3A>T were the most common variants predisposing to BC, and they are likely to be founder variants. Three frequent MUTYH pathogenic variants (c.884C>T, c.1437_1439delGGA and c.1187G>A) were responsible for all MUTYH biallelic cases (4.4% of high-risk CRC patients). The total pathogenic variant frequency was very low in controls (2.4%) and in low-risk BC (3.9%) and CRC (6.1%) patients. Our study depicts the pathogenic variant spectrum and prevalence in Turkish BC and CRC patients, guiding clinicians and health authorities for genetic testing applications and variant classification in Turkish population.

Hepatocellular adenomas in the Turkish population: reclassification according to updated World Health Organization criteria.

AIMS: Hepatocellular adenoma (HCA) is an uncommon liver neoplasm, and studies of HCA subtypes have been primarily limited to France, the USA, and Japan. The aim of this study was to describe the clinicopathological features of HCA subtypes in Turkey. METHODS AND RESULTS: The resection specimens of 59 cases diagnosed as 'hepatocellular adenoma' collected from 15 institutions were reviewed to confirm the diagnosis and to classify them according to the current World Health Organization 2019 classification. Immunostaining for glutamine synthetase, liver fatty acid-binding protein, C-reactive protein, ß-catenin and reticulin was performed. Of the 59 cases, 48 (81%) were diagnosed as HCA. We identified 24 (50%) hepatocyte nuclear factor 1α (HNF1α)-inactivated HCAs, five (10%) inflammatory HCAs, 15 (32%) ß-catenin-activated HCAs, three (6%) ß-catenin-activated inflammatory HCAs, and one (2%) unclassified HCA. HCA patients were predominantly female (female/male ratio of 5:1); they had a median age of 34 years and a median tumour diameter of 60 mm. In the ß-catenin-activated HCA group, nine cases (19%) showed cytoarchitectural atypia, and were also referred to as atypical hepatocellular neoplasms. In the ß-catenin-activated HCA group, three cases (6%) showed focal areas supportive of transition to HCA. The original diagnosis of HCA was changed to well-differentiated hepatocellular carcinoma in nine cases and to focal nodular hyperplasia in two cases. CONCLUSION: In our series, the major HCA subtype was HNF1α-inactivated HCA. We found a low incidence of inflammatory-type HCA. Our data also showed that ß-catenin-activated hepatocellular neoplasms, including cases with atypical histology, constituted a relatively high proportion of the cases. These findings are in contrast to those of most other studies of HCA subtypes.

PD-L1 Expression in Mismatch Repair-deficient Endometrial Carcinoma and Tumor-associated Immune Cells: Differences Between MLH1 Methylated and Nonmethylated Subgroups.

Mismatch repair (MMR)-deficient endometrial carcinomas show increased programmed cell death-ligand 1 (PD-L1) expression compared with MMR-intact endometrial carcinomas, but there are limited data regarding PD-L1 expression between sporadic and inherited carcinomas exhibiting MMR loss. Most of the studies investigating PD-L1 expression in endometrial carcinoma have used tissue microarrays and did not examine all tumor blocks. In this study, we analyzed the expression of PD-L1 in resection specimens of 176 consecutive endometrial carcinomas using all tumor blocks; we compared PD-L1 expression in MMR-deficient endometrial carcinomas, including the MLH1 and PMS2-loss subgroup, and the other MMR-loss subgroups (MSH2 and MSH6, isolated PMS2, and isolated MSH6), with the MMR-intact subgroup. MLH1 methylation was performed in tumors with MLH1 and PMS2 loss. Tumor cell (TC) and tumor-associated immune cell (IC) PD-L1 positivity with a 1% cutoff was observed in 21% (n=37) and 66.5% (n=117) of cases, respectively, and with a 5% cutoff in 5.1% (n=9) and 39.8% (n=70) of cases, respectively. MMR protein deficiency was a statistically significant parameter associated with IC PD-L1 positivity, with 1% and 5% cutoffs on multivariate analysis [odds ratio (OR)=5.236, 95% confidence interval (CI)=2.075-13.211, P=0.001, and OR=3.702, 95% CI=1.759-7.791, P=0.001, respectively]. The multivariate analysis showed that IC PD-L1 positivity, using both 1% and 5% cutoffs, was significantly associated with the MLH1 and PMS2 loss compared with the MMR protein-intact subgroup (MLH1 and PMS2 loss for 1% cutoff: OR=5.104, 95% CI=1.876-13.881, P=0.001, and for 5% cutoff: OR=3.322, 95% CI=1.540-7.166, P=0.002). Squamous differentiation was an independent predictor for TC PD-L1 positivity, with a 5% cutoff (OR=6.102, 95% CI=1.280-10.096, P=0.026). Larger tumor size was an independent predictive factor for IC PD-L1 positivity with a 1% cutoff (OR=6.757, 95% CI=1.569-29.109, P=0.010). Overall, 48 (92.3%) of 52 MLH1 methylated tumors showed IC PD-L1 positivity with 1% cutoff, and 34 (65.4%) of 52 MLH1 methylated tumors showed IC PD-L1 positivity with 5% cutoff. Our results show a higher rate of IC PD-L1 positivity than in previous studies. This is likely due in part to the use of all tumor blocks. MLH1 and PMS2 loss was an independent predictive factor for IC PD-L1 positivity, with both 1% and 5% cutoffs. Using univariate analysis, we observed decreased disease-free survival for IC PD-L1 positivity ≥5%. Our study results should now be tested and proven in larger cohorts, with longer follow-up data.

KRAS-mutated Uterine Endometrioid Carcinoma With Extensive Surface Changes Resulting in Striking Morphologic Mimicry of an Ovarian Serous Borderline Tumor.

Surface epithelial changes involving endometrioid carcinomas of the uterine corpus mimicking papillary syncytial metaplasia or cervical microglandular hyperplasia are relatively common. There have been rare reports of surface epithelial changes in endometrioid carcinomas mimicking ovarian serous borderline tumor or low-grade serous carcinoma. We report an endometrioid carcinoma of the uterine corpus with striking morphologic mimicking of an ovarian serous borderline tumor with only a minimal amount of conventional endometrioid carcinoma. The tumor was diffusely positive for estrogen receptor, negative for WT1, and showed wild-type immunoreactivity with p53. Targeted sequencing revealed a KRAS mutation (G12V/D/A), but no BRAF mutation. This close mimicry of a serous borderline tumor by a uterine endometrioid carcinoma has not been emphasized in the literature and this case is unique because the features involved almost the entire neoplasm. In reporting this case, we review surface changes in endometrioid carcinomas of the uterine corpus.

Determining the cut-off values of tumor diameter, degree of extraprostatic extension, and extent of surgical margin positivity with regard to biochemical recurrence of prostate cancer after radical prostatectomy.

BACKGROUND: The pre-biopsy (bx) prostate-specific antigen (PSA) level, tumor volume/diameter, degree of extraprostatic extension (EPE), and extent of surgical margin positivity have been shown to be significant prognostic parameters of biochemical recurrence (BCR) after radical prostatectomy. The present study assessed the cut-off values of the pre-bx PSA level, maximum tumor diameter, radial and circumferential distances of EPE, and circumferential length of surgical margin (SM) positivity with regard to BCR. MATERIAL AND METHODS: The study included 445 radical prostatectomy specimens, and the cut-off values of all parameters were determined using receiver operating characteristic curve analysis. RESULTS: An ISUP grade group ≥ 3, radial distance of EPE >1 mm, and circumferential length of SM positivity ≥2 mm were identified as independent predictors of BCR after radical prostatectomy. The parameters that showed statistical significance in univariate analysis, such as pre-bx PSA level ≥ 7.20 ng/mL, tumor diameter ≥ 19.5 mm, presence of seminal vesicle invasion, and circumferential distance of EPE >3 mm, did not have independent prognostic values for BCR. CONCLUSIONS: An ISUP grade group ≥ 3, radial distance of EPE >1 mm, and circumferential length of SM positivity ≥2 mm are predictors of BCR. Our findings might have significance in risk classification and adjuvant therapy consideration among patients with localized prostate cancer.

Evaluation of the Effect of Topical Application of Nigella sativa on Acute Radiation-Induced Nasal Mucositis.

The goal of this study was to demonstrate the effect of radiotherapy (RT) on nasal mucosa in rats and to evaluate the radioprotective effects of the topical application of black seed oil (Nigella sativa [NS]) to treat acute radiation-induced nasal mucositis.A total of 18 rats were randomized into 3 groups, with 6 animals per group. The rats in group 1 were topically administered saline in the nasal cavity after sham irradiation. Group 2 received saline at the same dose after irradiation. Group 3 was given NS after irradiation. The rats in groups 2 and 3 were irradiated with a single dose of 40 Gy to the nasal and paranasal area. Only one drop of saline (0.05 mL) was applied to each nostril in the first, second, and third days after RT in groups 1 and 2. One drop of cold press NS (0.05 mL) was applied to each nostril in group 3. Fourteen days after irradiation, the nasal mucosal tissues were excised for histopathological evaluation. Vascular dilatation, inflammatory cell infiltration, superficial erosion, and formation of exudates were classified according to the severity.No evidence of mucositis was observed in group 1. Of all the parameters the only statistically significant difference between groups 2 and 3 were observed for "superficial erosion' (P < 0.05). Overall microscopic observations in the NS-treated group were better than in group 2.The preliminary results of our study have shown that local application of NS to the nasal mucosa may be an effective treatment of acute nasal mucositis due to RT.

Proteomic profiling of HBV infected liver biopsies with different fibrotic stages.

BACKGROUND: Hepatitis B virus (HBV) is a global health problem, and infected patients if left untreated may develop cirrhosis and eventually hepatocellular carcinoma. This study aims to enlighten pathways associated with HBV related liver fibrosis for delineation of potential new therapeutic targets and biomarkers. METHODS: Tissue samples from 47 HBV infected patients with different fibrotic stages (F1 to F6) were enrolled for 2D-DIGE proteomic screening. Differentially expressed proteins were identified by mass spectrometry and verified by western blotting. Functional proteomic associations were analyzed by EnrichNet application. RESULTS: Fibrotic stage variations were observed for apolipoprotein A1 (APOA1), pyruvate kinase PKM (KPYM), glyceraldehyde 3-phospahate dehydrogenase (GAPDH), glutamate dehydrogenase (DHE3), aldehyde dehydrogenase (ALDH2), alcohol dehydrogenase (ALDH1A1), transferrin (TRFE), peroxiredoxin 3 (PRDX3), phenazine biosynthesis-like domain-containing protein (PBLD), immuglobulin kappa chain C region (IGKC), annexin A4 (ANXA4), keratin 5 (KRT5). Enrichment analysis with Reactome and Kegg databases highlighted the possible involvement of platelet release, glycolysis and HDL mediated lipid transport pathways. Moreover, string analysis revealed that HIF-1α (Hypoxia-inducible factor 1-alpha), one of the interacting partners of HBx (Hepatitis B X protein), may play a role in the altered glycolytic response and oxidative stress observed in liver fibrosis. CONCLUSIONS: To our knowledge, this is the first protomic research that studies HBV infected fibrotic human liver tissues to investigate alterations in protein levels and affected pathways among different fibrotic stages. Observed changes in the glycolytic pathway caused by HBx presence and therefore its interactions with HIF-1α can be a target pathway for novel therapeutic purposes.

Outcomes of Gleason score 3 + 4 = 7 prostate cancer with minimal amounts (<6%) vs ≥6% of Gleason pattern 4 tissue in needle biopsy specimens.

OBJECTIVE: The International Society of Urological Pathology Gleason grading system was modified in 2005. Since the modified system was introduced, many cancers that previously would have been categorized as Gleason score (GS) 6 are now categorized as GS 7 based on biopsy specimens that only contain minimal amounts (<6%) of Gleason pattern (GP) 4 tissue. However, the clinical significance of observing <6% of GP 4 tissue in biopsies of GS 7 prostate cancer has not been studied. MATERIAL AND METHODS: This study was based on needle biopsy specimens that were categorized as GS 6 or GS 7 and were obtained from patients who underwent radical prostatectomy (RP) with available follow-up data. We assessed the quantity of GP 4 tissue in biopsy specimens of GS 7 prostate cancer. Further, we evaluated the correlation between the quantity of GP 4 tissue and disease progression after RP. RESULTS: GP 4 comprising 26-49% of the specimen, GS 4+3 and percentage of total core tissue scored as positive were significant and independent predictors of prostate-specific antigen (PSA) failure after RP, as assessed using a multivariate Cox regression model that included the quantity of GP 4 in the prostate biopsy specimen, preoperative PSA, perineural invasion, clinical stage, number of positive cores, and percentage of core tissue scored as positive. Cases with GS 3+3 and cases in which the observed GP 4 area was <6% did not differ significantly in terms of biochemical PSA recurrence (BPR) status. In contrast, cases with 6-25% GP 4 tissue, 26-49% GP 4 tissue, and GS 4+3 showed more frequent BPR than cases with GS 3+3. CONCLUSIONS: Our data suggest that the quantity of GP 4 tissue in GS 7 cancer has clinical significance. However, there is a need for larger studies of the clinical significance of biopsy specimens that include <6% GP 4 tissue. We should reconsider whether the amount of GP 4 should be included in standart pathology reports.

Significance of foamy histiocytes in cervical smears from postmenopausal women.

OBJECTIVE: To determine the significance of the presence of foamy histiocytes (FH) in postmenopausal cervicovaginal smears for the detection of endometrial carcinomas (EC). STUDY DESIGN: Endometrial sampling was performed over 6 months in 53 of 102 cases that presented with postmenopausal FH, benign endometrial cells (BEC), FH with BEC (FH + BEC), and atypical endometrial cells (AEC), resulting in a total of 41,150 cervicovaginal smears. The control group consisted of 58 cases with a cytologic diagnosis of a normal smear (NS). RESULTS: There were 0 (0%), 1 (4.54%), 2 (13.33%), 2 (33.33%), and 5 (50.00%) cases of EC diagnosed on histopathologic evaluation in patients with NS (n = 58), BEC (n = 22), FH (n = 15), FH + BEC (n = 6), and AEC (n = 10), respectively. The sensitivities and specificities of the cytologic diagnoses of FH, FH + BEC, and AEC for the detection of EC were 81.7 and 100%, 93.6 and 100%, and 92.1 and 100%, respectively. CONCLUSION: The cytologic diagnoses of FH and FH + BEC had reasonably high sensitivities and specificities for the diagnosis of EC by cervicovaginal smear. Additional studies are needed.

Is the low-grade squamous intraepithelial lesion/atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion category associated with cervical intraepithelial neoplasia 2?

OBJECTIVE: A number of cervical smears may exhibit unequivocal low-grade squamous intraepithelial lesions (LSIL) in association with atypical cells cytomorphologically suspicious, but not sufficient to be interpreted as high-grade squamous intraepithelial lesions (HSIL). These lesions are presently called LSIL, atypical squamous cells cannot exclude HSIL (LSIL/ASC-H). Previous studies have shown that LSIL/ASC-H and ASC-H are both equivocal for HSIL and have a high risk of underlying HSIL. However, in researching the literature only two studies were found which rendered the results as cervical intraepithelial neoplasia (CIN) 2 and CIN3 separately. The purpose of this study was to compare the distribution of biopsy results for CIN2 and CIN3 in patients with ASC-H, HSIL, and LSIL/ASC-H. STUDY DESIGN: Between January 2005 and December 2011, cervicovaginal smears (98,594) with a diagnosis of ASC-H, LSIL, LSIL/ASC-H, or HSIL were re-evaluated to determine the prevalence of future lesion development. RESULTS: A total of 252 patients who had histologic follow-up within a year were selected. Among these, LSIL/ASC-H (31.7%) had the highest prevalence of CIN2 between LSIL (9.3%), ASC-H (10%), and HSIL (16%). All differences were statistically significant. CONCLUSION: Because of the high predictive value of CIN2, LSIL/ASC-H may have further importance, especially in women of different age groups.

Histopathologic Follow-Up of Women with Inadequate ThinPrep™ Cervical Pap Tests and Positive High-Risk Human Papillomavirus Test Results.

INTRODUCTION: We found only a few studies that had performed high-risk human papillomavirus (hrHPV) analyses of inadequate ThinPrep™ Papanicolaou (Pap) tests. Therefore, this study aimed to analyze unsatisfactory ThinPrep Pap tests using hrHPV tests. The colposcopic biopsy results of cases with an unsatisfactory ThinPrep Pap test and positive hrHPV results were revealed. METHODS: Between January 1, 2018, and October 31, 2022, 965 (3.7%) of 25,958 liquid-based cytology specimens were evaluated as unsatisfactory. Ninety-five (9.8%) of 965 patients were positive for hrHPV. The colposcopic evaluation was performed in 28 (29.4%) of 95 patients, in whom 23 tests were adequate. RESULTS: Twenty-three colposcopy biopsy results showed that 17 (73.9%) of 23 patients had benign biopsy results. High-grade squamous intraepithelial lesions were observed in three (13%) of the 23 patients, and low-grade squamous intraepithelial lesions were observed in two (8.6%) of the 23 patients. One of the 23 (4.3%) patients had keratinized squamous cell carcinoma of the cervix diagnosed histologically, although no tumor was visible upon gynecologic examination. CONCLUSION: For the management of unsatisfactory Pap tests, The American Society for Colposcopy and Cervical Pathology (ASCCP) recommends repeat cytology within 2-4 months. Evaluation of such patients using hrHPV tests may triage those with squamous intraepithelial lesions, even invasive cervical cancer. More studies with a larger number of cases are needed to analyze the hrHPV status and biopsy follow-up of cases with unsatisfactory cytology.

Immediate histopathologic correlation in Turkish population with negative cytology and high-risk human papillomavirus positivity: A retrospective analysis of high-risk human papillomavirus genotype and stratified by age.

INTRODUCTION: According to the American Society of Colposcopy and Cervical Pathology (ASCCP) recommendations, regardless of age, women with high-risk infections other than human papillomavirus 16/18 positivity (other hrHPV) and negative cytology should not be referred directly to colposcopy. Several studies compared detection rates of ≥high-grade squamous intraepithelial lesion (HSIL) between HPV 16/18 ± 45, and other hrHPV types on colposcopic biopsy. METHODS: We designed a retrospective study to determine the presence of ≥HSIL in colposcopic biopsy in women with negative cytology and hrHPV positivity during the years 2016-2022. RESULTS: HPV 16/18/45 had a PPV of 43.8%, while other hrHPV types had a PPV of 29.1% for a tissue diagnosis of ≥HSIL. For a tissue diagnosis of ≥HSIL detection, there was no statistically significant difference between the PPV of other hrHPV and HPV 16/18/45 in patients ≥30. There were only two cases with a tissue diagnosis of ≥HSIL in the other hrHPV group of women under 30 years of age. CONCLUSION: We suggested that the follow-up recommendations of ASCCP for patients above the age of 30 with negative cytology and other hrHPV positivity may not be fully applicable to countries like Turkey with a different healthcare environment. Referring to patients ≥30 who had other hrHPV positivity and negative cytology to direct colposcopy may be clinically beneficial, particularly in populations where a colposcopic examination is easy and inexpensive.

Comparison of the Clinical Performance of Aptima HPV Assay and the Cobas 4800 Platform in Women with Normal Cytology and Positive High-Risk HPV.

INTRODUCTION: According to the current American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines, patients with normal cytology results may be referred for colposcopy according to their high-risk human papillomavirus (hrHPV) test results. A higher positive predictive value (PPV) of hrHPV has significance for preventing unnecessary colposcopic examinations. Several studies have compared the performance of the Aptima assay and the Cobas 4800 platform among patients who had minor cytologic abnormalities. However, in our English literature search, we found no other study that had been conducted to compare these two methods in patients with normal cytology. We thus aimed to compare the PPV of the Aptima assay and the Cobas 4800 platform among women with normal cytology. METHODS: Between September 2017 and October 2022, we retrospectively identified 2,919 patients who had normal cytology and hrHPV positivity and had been referred for a colposcopy. Among them, 882 agreed to undergo a colposcopy; on examination, 134 had target lesions revealed and underwent a colposcopic punch biopsy. RESULTS: Among the patients who underwent a colposcopic punch biopsy, 49 (38.9%) were tested with Aptima, and 77 (61.1%) were tested with Cobas. In the Aptima group, 29 (59.2%) patients showed benign histology, 2 (4.1%) patients had low-grade squamous intraepithelial lesions (LSILs), and 18 (36.7%) patients had ≥high-grade squamous intraepithelial lesions (HSILs) biopsy results. The false-positivity rate and PPV of Aptima were 63.3% (31/49) and 36.7% (95% confidence interval [CI]: 0.232-0.502), respectively, for a histopathologic diagnosis of ≥HSIL. In the Cobas group, 48 (62.3%) biopsies were benign, 11 (14.3%) reported an LSIL, and 18 (23.4%) biopsies were ≥HSIL. The false-positivity rate and PPV of Cobas were 76.6% (59/77) and 23.4% (95% CI: 0.139-0.328), respectively, concerning a ≥HSIL tissue diagnosis. The false-positivity rate of Aptima HPV 16 positivity was 40% (4/10). The false-positivity rate of Cobas HPV 16 positivity was 61.1% (11/18). The PPVs of HPV 16 positivity for Aptima and Cobas were 60% (95% CI: 0.296-0.903) and 38.9% (95% CI: 0.163-0.614), respectively, concerning ≥HSIL tissue diagnosis. CONCLUSION: We recommend analyzing the performances of hrHPV platforms in future, larger studies in patients with normal cytology rather than only in cases with abnormal cytology.

High-risk human papillomavirus (HPV) detection in formalin-fixed paraffin-embedded cervical tissues: performances of Aptima HPV assay and Beckton Dickinson (BD) Onclarity assay.

AIM: There are many scenarios where high-risk human papillomavirus (HPV) detection in formalin-fixed paraffin-embedded (FFPE) specimens is important. However, there is no Food and Drug Administration (FDA)-approved and clinically validated technique for detecting high-risk HPV in FFPE tissues. In this study, we evaluated two commercially available HPV assays which are FDA-approved for use on cytology specimens, the Aptima HPV assay and the Beckton Dickinson (BD) Onclarity assay, to detect high-risk HPV in FFPE tissues of cervical high-grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma (SCC). METHODS: A total of 189 cases (46 SCC, 107 HSIL and 36 benign/normal) were tested for high-risk HPV with the Aptima HPV assay and a subset of cases (n=97) with the BD Onclarity assay. RESULTS: The sensitivities of the Aptima and BD Onclarity HPV assays were 99.4% (95% CI 96.46% to 99.98%) and 75.9% (95% CI 65.27% to 84.62%), respectively; the specificity and positive predictive value (PPV) of the two assays were 100%. Negative predictive values of the Aptima and BD Onclarity HPV assays were 97.3% (95% CI 83.61% to 99.61%) and 67.7% (95% CI 58.91% to 75.47%), respectively. The kappa value (0.96) for comparison of the distribution of high-risk HPV types between the two assays was high. HPV 16 was the most common high-risk HPV type for HSIL and SCC cases. However, SCC cases had higher percentages of HPV 16 and HPV 18/45 and lower percentages of other high-risk HPV types compared with HSIL cases. CONCLUSION: Both assays are reliable methods for high-risk HPV detection and genotype determination in FFPE specimens, with high PPV and specificity. The Aptima HPV assay has the advantage of higher sensitivity. As far as we are aware, this is the first study comparing the Aptima HPV assay and the BD Onclarity assay in FFPE tissues. Our study results should be tested and confirmed in larger cohorts.