Diagnosis Of Squamous Intraepithelial Lesions Research Articles

Intraepithelial CD15 infiltration identifies high-grade anal dysplasia in people with HIV.

Men who have sex with men (MSM) with HIV are at high risk for squamous intraepithelial lesion (SIL) and anal cancer. Identifying local immunological mechanisms involved in the development of anal dysplasia could aid treatment and diagnostics. Here, we studied 111 anal biopsies obtained from 101 MSM with HIV, who participated in an anal screening program. We first assessed multiple immune subsets by flow cytometry, in addition to histological examination, in a discovery cohort. Selected molecules were further evaluated by immunohistochemistry in a validation cohort. Pathological samples were characterized by the presence of resident memory T cells with low expression of CD103 and by changes in natural killer cell subsets, affecting residency and activation. Furthermore, potentially immunosuppressive subsets, including CD15+CD16+ mature neutrophils, gradually increased as the anal lesion progressed. Immunohistochemistry verified the association between the presence of CD15 in the epithelium and SIL diagnosis for the correlation with high-grade SIL. A complex immunological environment with imbalanced proportions of resident effectors and immune-suppressive subsets characterized pathological samples. Neutrophil infiltration, determined by CD15 staining, may represent a valuable pathological marker associated with the grade of dysplasia.

The diagnosis and management of vulval intraepithelial neoplasia

Key content High‐risk human papilloma virus (HPV)‐associated vulval high‐grade squamous intraepithelial lesions and HPV‐independent differentiated vulval intraepithelial lesions represent distinct disease processes with different risks of progression to vulval squamous cell carcinoma. First‐line medical management is appropriate for women with biopsy‐confirmed vulval high‐grade squamous intraepithelial lesions who have been adequately counselled on the risk of occult invasive disease. Topical treatment should be undertaken in the context of a specialist clinic because it is not suitable for all patients. Surgical management is needed for differentiated vulval intraepithelial neoplasia. Learning objectives To understand the clinical, histological, and pathological classification of squamous intraepithelial lesions and diagnostic challenges. To be able to contribute to the multidisciplinary investigation and diagnosis of squamous intraepithelial lesions. To understand the basis for patient‐centred counselling on the investigation, diagnosis and treatment of suspected squamous intraepithelial lesions. Ethical issues Treatment must be tailored towards the patient's appreciation of risk and benefit, informed by the clinical and pathological features of the disease.

Trichomonas vaginalis infection is associated with increased risk of cervical carcinogenesis: A systematic review and meta-analysis of 470 000 patients.

Trichomonas vaginalis infection is the most prevalent non-viral sexually transmitted infection (STI) in women and has been suggested as a risk factor for developing cervical cancer. We aimed to investigate the associations between T. vaginalis infection and cervical carcinogenesis. A comprehensive systematic search was conducted in five databases on 21 October 2021. Studies assessing the relationship between T. vaginalis infection, HPV co-infections, cervical dysplasia, and cervical cancer were found eligible. Summary estimates for pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated with a random-effects model. Statistical heterogeneity was measured with I2 and Cochran's Q tests. The 29 articles included 473 740 women, of whom 8518 were T. vaginalis-positive. Our results showed that T. vaginalis-infected women had 1.79 times higher odds of being diagnosed with HPV co-infection (95% CI 1.27-2.53; I2 95%). We also found that T. vaginalis infection was associated with high-grade squamous intraepithelial lesion diagnosis (OR 2.34, 95% CI 1.10-4.95; I2 75%) and cervical cancer (OR 5.23, 95% CI 3.03-9.04; I2 3%). Our results showed an association between T. vaginalis and cervical carcinogenesis in sexually active women.

P16INK4A flow cytometry of exfoliated cervical cells: Its role in quantitative pathology and clinical diagnosis of squamous intraepithelial lesions.

P16INK4A is a surrogate signature compensating for the specificity and/or sensitivity deficiencies of the human papillomavirus (HPV) DNA and Papanicolaou smear (Pap) co-test for detecting high-grade cervical squamous intraepithelial lesions or worse (HSIL+). However, traditional p16INK4A immunostaining is labour intensive and skill demanding, and subjective biases cannot be avoided. Herein, we created a high-throughput, quantitative diagnostic device, p16INK4A flow cytometry (FCM) and assessed its performances in cervical cancer screening and prevention. P16INK4A FCM was built upon a novel antibody clone and a series of positive and negative (p16INK4A -knockout) standards. Since 2018, 24100-women (HPV-positive/-negative, Pap-normal/-abnormal) have been enrolled nationwide for two-tier validation work. In cross-sectional studies, age- and viral genotype-dependent expression of p16INK4A was investigated, and optimal diagnostic parameter cut-offs (using colposcopy and biopsy as a gold standard) were obtained. In cohort studies, the 2-year prognostic values of p16INK4A were investigated with other risk factors by multivariate regression analyses in three cervicopathological conditions: HPV-positive Pap-normal, Pap-abnormal biopsy-negative and biopsy-confirmed LSIL. P16INK4A FCM detected a minimal ratio of 0.01% positive cells. The p16INK4A -positive ratio was 13.9±1.8% among HPV-negative NILM women and peaked at the ages of 40-49 years; after HPV infection, the ratio increased to 15.1±1.6%, varying with the carcinogenesis of the viral genotype. Further increments were found in women with neoplastic lesions (HPV-negative: 17.7±5.0-21.4±7.2%; HPV-positive: 18.0±5.2-20.0±9.9%). Extremely low expression of p16INK4A was observed in women with HSILs. As the HPV-combined double-cut-off-ratio criterion was adopted, a Youden's index of 0.78 was obtained, which was significantly higher than that (0.72) of the HPV and Pap co-test. The p16INK4A -abnormal situation was an independent HSIL+ risk factor for 2-year outcomes in all three cervicopathological conditions investigated (hazard ratios: 4.3-7.2). FCM-based p16INK4A quantification offers a better choice for conveniently and precisely monitoring the occurrence of HSIL+ and directing risk-stratification-based interventions.

A Pilot Study of a Screening Program for Human Papillomavirus-Related Squamous Intraepithelial Lesion and Malignancy in Gynecologic Oncology Patients.

Human papillomavirus (HPV)-related squamous intraepithelial lesion (SIL) or malignancy is associated with a significantly increased risk of second-site SIL or malignancy. The primary objective of this study was to determine the feasibility and acceptability of concurrent anal, cervical, and vulvovaginal screening in patients with a history of HPV-related gynecologic high-grade SIL or malignancy. The secondary objective was to assess subjects' knowledge regarding HPV screening and risks. Women with high-grade cervical, vulvar, or vaginal SIL or malignancy were enrolled during a 1-year pilot period. Subjects with cervical SIL or malignancy underwent vulvar examination and anoscopy. Subjects with vulvovaginal SIL or malignancy underwent Pap test if indicated and anoscopy. Appropriate referrals were made for abnormal findings. Feasibility was assessed by compliance using study acceptance rate, screening procedure adherence, and referral adherence. Acceptability was assessed using a Likert-scaled question after completion of screening procedures. One hundred three women with a diagnosis of high-grade vulvovaginal or cervical SIL or carcinoma were approached regarding study enrollment; of these, 74 (71.8%) enrolled. The median score on the HPV knowledge assessment was 8.1 ± 1.6 (max score 10). Seventy-three (98.6%) of 74 patients rated the screening procedures as acceptable (score of 5/5). On examination, 14 (18.9%) subjects had abnormalities noted; 7 (9.5%) were referred for colorectal surgical evaluation, and 6/7 (85.7%) were compliant with their referral appointments. Screening examinations for other HPV-related SILs and malignancies, including Pap tests, vulvovaginal inspection, and anoscopy, are acceptable to patients, with abnormal findings in almost 1 in 5 women.

Cervical Pre-cancers: Biopsy and Immunohistochemistry.

The existence of precursor lesions for invasive cervical cancer has been recognized for more than 50 years. Our understanding of the pathobiology and behavior of cervical cancer precursors has evolved considerably over the past five decades. Furthermore, the terminology used to classify pre-invasive lesions of the cervix has frequently changed. The realization that human papillomavirus (HPV) infections constitute a morphologic continuum has prompted efforts to include them within a single classification system, specifically the squamous intraepithelial lesions (SILs) which have now been embraced by the surgical pathologists. The reduced number of specific pathological categories has made clinical decision-making more straightforward. The generic criteria for SIL have two important histological parameters: Alterations in the density of superficial epithelial cells and superficial squamous atypia. The flat condyloma or cervical intraepithelial neoplasia (CIN) I is generally associated with intermediate and high-risk HPV types as against the low-risk viruses that cause exophytic/papillary growth patterns of condylomas. The diagnosis of low-grade SIL (LSIL) (flat and exophytic condylomas) requires first excluding benign mimics of LSIL and second to confirm the characteristic cytologic atypia. For high-grade SILs (HSILs), the extent and degree of atypia generally exceed the limits of that described in flat or exophytic condylomas (LSILs). Less maturation, abnormal cell differentiation, loss of cell polarity, and increased mitotic index with abnormal mitotic figures occupying increasing thickness of the epithelium define a lesion as CIN II or CIN III. Atypical immature metaplasia associated with inflammation and atrophy is a challenge in cervical biopsy interpretation. Careful attention to the growth pattern of the epithelium, the distribution of the atypia, nuclear spacing, and the degree of anisokaryosis and the presence of enlarged hyperchromatic nuclei help in differentiating a non-neoplastic from a neoplastic process. This chapter describes in depth the diagnostic difficulties in the interpretation of cervical biopsies. It also provides useful criteria in distinguishing benign mimics from true precancerous lesions and the role of biomarkers such as the p16ink4 and Ki-67 in the differential diagnosis of precursor lesions and the reactive and metaplastic epithelium.

The value of Ki67 for the diagnosis of LSIL and the problems of p16 in the diagnosis of HSIL

p16 and Ki67 are immunohistochemical markers related to cervical squamous intraepithelial lesions. p16 has been widely used to assist in the diagnosis of high-grade squamous intraepithelial lesions. However, a conclusion about the role of Ki67 in the diagnosis of squamous intraepithelial lesions has not been established. The aim of this study was to analyze the role of p16 and Ki67 immunohistochemical staining in assisting cervical squamous intraepithelial lesions. This study performed immunohistochemical staining for p16 and Ki67 on 1024 cervical biopsy specimens at our hospital to compare the differences between p16 and Ki67 in different cervical lesions using the chi-squared test and Fisher’s exact test. This study also evaluated the value of Ki67 for the diagnosis of low-grade squamous intraepithelial lesions (LSILs) using the receiver operating characteristic curve. The results indicated that Ki67 had high specificity and sensitivity in distinguishing LSIL from normal cervix. p16 was diffusely and strongly positive in some LSILs, and some problems were encountered in the interpretation of p16 staining. Therefore, we believe that Ki67 can be used as an immunohistochemical marker to help in the diagnosis of LSIL, to distinguish lesions that are difficult to morphologically determine and to avoid misdiagnosis. The practical application of p16 staining is still problematic. It may be necessary to find other auxiliary means to distinguish this small proportion of cervical lesions.

Поиск маркеров при ВПЧ-ассоциированных поражениях шейки матки методом хромато-масс-спектрометрии

Study Objective: To study the lipid composition of cervical epithelium in HPV-associated lesions in order to search for markers for early noninvasive diagnosis of squamous intraepithelial lesions (SIL) of the cervix. Study Design: cross-sectional prospective cohort study. Materials and Methods. The study included 124 patients aged 21 to 45 years old. For scraping of the epithelium in the cervix and cervical canal, a cervical brush was used. The lipidic extract from a scraping sample was analysed with the use of chromatography-mass spectrometry (positive and negative ions). Possible markers were searched for with the help of the Mann-Whitney test and analysis of views for hidden structures; logistic regression variables were selected based on the Akaike information criterion. The models were tested with cross validation of a separate item. Study Results. We have identified lipids belonging to cholesterol esters, phosphatidylcholines, ceramides and sphingomyelins, which allow differentiating between normal conditions, cervicitis, high- and low-grade SIL, and cervical cancer. The model accuracy for positive and negative ion modes was 70% and 71%, respectively. The final model accuracy was 79% and demonstrated high predicative value for cervicitis and cervical cancer and moderate predicative value for low-grade SIL vs. norm. Conclusion. The potential for non-invasive cervical SIL differentiation using lipid markers has been demonstrated. Keywords: neoplastic lesions, cervical cancer, lipids, diagnosis.

Non-human papilloma virus associated adenocarcinomas of the cervix uteri. Cytologic features and diagnostic agreement using whole slide digital cytology imaging.

Non-Human Papilloma Virus associated adenocarcinomas (NHPVAs) are uncommon tumors of the cervix uteri which often show a deceptive morphology. Therefore, their diagnostic assessment may be challenging. Slide digital cytology imaging may be an useful tool to improve cytological diagnostic accuracy. However, this novel technology has not been applied to NHPVAs associated cytologies yet. The study included 31 whole slide digital cytology cases from 10 women with a proven histological diagnosis of NHPVA. As a control group, three further digital slides, from two women with a histological diagnosis of squamous intraepithelial lesion (SIL), were included. The digitally scanned cytological slides were revised to assess the concordance rate among three observers and to find out the most relevant NHPVA cytological criteria. Overall diagnostic agreement between observers was 67.60% (K = 0.50; P < 0.0001). At the consensus diagnosis 34 cases were re-classified as at least suspicious for glandular lesion (n = 24), SIL (n = 2) and negative (n = 8). The most relevant cytologic features for atypical glandular cells or adenocarcinoma at consensus were evident nucleoli, nuclear overlapping and atypical enlarged nuclei. The diagnosis of NHPVA in digital cytology is feasible using criteria which are also used in conventional microscopy. Our study shows a moderate agreement for the cytological diagnosis of NHPVAs using whole slide digital cytology approach. These results are discussed taking into account the most relevant differential diagnostic issues.

P16 Immunostaining Can Eliminate Approximately 20% Inaccurate Diagnosis of Low-Grade Squamous Intraepithelial Lesions (SIL) in Cervical Biopsies

Abstract Introduction/Objective Differentiating low-grade SIL from reactive changes on light microscopy has remained controversial. P16 immunostaining is widely accepted in high-grade SIL unlike in low-grade SIL. We focused on the use of p16 immunostaining in eliminating inaccurate diagnosis of low-grade SIL on light microscopy. Methods A retrospective study on 60 cervical biopsies results over a 2 year-period was conducted using 35 suspicious cases for low-grade SIL (bi-nucleation and some nuclear atypia) and 25 low suspicion cases (enlarged nuclei but nuclear atypia cannot differentiate from reactive changes). All cases were stained for p16, significant nuclear expression of p16 was determined as low- grade SIL. Results After p16 immunostaining, 30/35 (85%) cervical biopsies from the suspicious group were found to be truly positive for low-grade SIL while 5/35 (15%) biopsies negative for p16 immunostaining were regarded as reactive changes. In the low suspicious group, 7/25 (28%) were found to be positive for low-grade SIL and 18/25 (72%) biopsies were negative, favoring reactive changes. The overall percentage of all 60 biopsies that showed a changed diagnosis based on p16 immunostaining was 20% (5 were truly negative in the suspicious group and 7 were truly positive in the low suspicious group). Using a 2 x 2 table with p16 as a gold standard for all biopsies, sensitivity and specificity of light microscopy for low-grade SIL were only 81% and 78% respectively. Conclusion Our study showed that p16 immunostaining can also be utilized to eliminate inaccurate diagnosis of low- grade SIL up to 20% in cervical biopsies.

Risk Factors for Malignant Transformation of Squamous Intraepithelial Lesions

Squamous intraepithelial lesions (SIL) are persistent white and white-red lesions that may represent precursor lesions for invasive squamous cell carcinoma (SCC). SILs encompass epithelial hyperplasia/hyperkeratosis, dysplasia, and carcinoma in situ. Specific indicators within SILs would be helpful for risk determination and treatment decisions. The purpose of this study was to determine the risk of SIL transformation to SCC using clinical appearance, histology, and immunohistochemical staining of biomarkers. A retrospective cohort study was conducted of patients diagnosed with oral cavity SILs between 2002 and 2012. Subjects were identified using billing records and pathology reports. Subjects were included if they had a new diagnosis of SIL via biopsy, histologic blocks/slides available for review, and > 5 years of follow-up after biopsy. Subjects with an existing or previous diagnosis of SCC at time of SIL diagnosis were excluded. Subjects were divided into two groups: 1) Those with SILs who did not transform to SCC and 2) those who transformed. Predictor variables included demographics (gender, age) and medical history (history of tobacco, alcohol, betel nut use, immune status, history of radiation). Macroscopic lesion related variables were site, size, and clinical appearance (described as white, red, heterogenous red-white, ulcerated, or nodular). Microscopic lesion variables were severity of dysplasia, location of atypia within epithelium (lower one-third, lower two-third, or full thickness), mitotic index, and amount of apoptosis, nuclear pleomorphism, rete peg complexity, lichenoid chronic inflammation, and hyperkeratosis. Mitotic index was quantified as the number of mitotically active cells recorded per high-powered field (hpf, 400x). Apoptotic abundance, nuclear pleomorphism, and rete-peg complexity were graded on a semi-quantitative scale 1-5. Lichenoid inflammation and hyperkeratosis were assessed as present or absent. Immunohistochemical lesion variables were p53 and Ki-67 immunoreactivity and measured as amount of positively stained cells per hpf. The primary outcome variable was presence of SCC on a subsequent biopsy (i.e., transformation to SCC). All diagnostic slides were reviewed and rated by a head and neck pathologist (WCF). Statistical results were analyzed using a Chi2 test, Fisher exact test, and 2-tailed t-test. Statistical results were considered significant with a 95% confidence interval if they had a P-value less than .05. A total of 60 subjects (45%, 27 female) were included of which 38 (63%, 17 female) did not transform to SCC whereas 22 (37%, 10 female) transformed. Mean ages of groups 1 and 2 were 58.2 ± 12.0 and 63.1 ± 15.1 years, respectively (P = .202). There were no differences in medical history and lesion location. Mean size of the SIL in groups 1 and 2 was 234 mm2 and 228 mm2, respectively, (P = .957). Transformation was significantly higher for heterogeneous red/white lesions: 5 (13%) in group 1, 9 patients (42%) in group 2 (P = .014). Patients with severe dysplasia were more likely to transform with 10 in group 2 (45.5%) and 2 in group 1 (5.3%) [P = .0003]. Atypia limited to the lower one-third was less likely to transform (P = .0173). Increased apoptosis (P = .043) and rete peg complexity (P = .014) were associated with SCC transformation. There was no difference in immunohistochemical staining of Ki-67 between groups (P = .305). In conclusion, SILs that transformed to SCC were more likely to have a red-white appearance, severe dysplasia, atypia throughout the epithelium, greater apoptosis, and rete peg complexity. Ki-67 immunoreactivity was not associated with transformation. Ongoing evaluation of p53 will be reported. The presence of these factors may influence decision to excise a SIL vs surveillance.

Comparison of Diagnostic Methods in Detection of Squamous Cell Abnormalities in Iranian Women with Abnormal Pap's Smear Test and Associated Demographic and Issues.

Premalignant lesions of cervix have increased dramatically in recent years. Early diagnosis and management of abnormalities have an effective role in preventing the invasion of the disease and also in timely treatment. This study aimed to compare diagnostic methods in the detectionof squamous cell abnormalities with abnormal Pap smear test. This cross-sectional study was performed on 1000 women with abnormal Pap smears in 2007-2018. Sampling was performed with simple method. All samples were subjected to an immediate assessment of colposcopy and histopathology if suspected. The checklist included demographic information as well as symptoms, cytopathology, colposcopy and histopathology findings. Data analysis was performed using descriptive and statistical analysis (P<0.05). A significant relationship between histopathology and Pap smear findings was found (P=0.009), also there was a significant correlation between histopathology and colposcopy findings (P=0.001). However, there was no significant relationship between clinical symptoms and histopathology findings (p=0.8). Sensitivity , specificity , positive and negative predictive value of Pap smear were 43%, 65.9%, 75.4%, 32.2% and of colposcopy were 74.7%, 39.5%, 75%, 39.1%, and of clinical symptoms were 72.6%, 28.1%, 71.1%, 29.7%, respectively. Pap smear findings have the appropriate diagnostic accuracy in comparison with colposcopy and histopathology findings for screening and diagnosis of squamous intra-epithelial lesions. Also, there was higher sensitivity of colposcopy compared with Pap smear to detect cervical lesions. Therefore, it is advisable to use these methods simultaneously.

FOXP3 immunoregulatory gene variants are independent predictors of human papillomavirus infection and cervical cancer precursor lesions.

FOXP3 is a marker of the T regulatory (Treg) cell subset and drives its function and homeostasis. Its expression maintains the host immunosuppressive state that favors persistence of human papillomavirus (HPV) infection and squamous intraepithelial lesion (SIL) appearance. The present study evaluated the effects of the rs3761548 and rs2232365 intronic single-nucleotide variants (SNVs) and their haplotypes on HPV infection and SIL diagnosis in HPV-infected and -uninfected women. HPV DNA-based detection in cervical specimens was performed by PCR. FOXP3 variants were genotyped by PCR-restriction fragment length polymorphism and haplotype recombination sites were inferred for 208 HPV-infected and 218 HPV-uninfected women diagnosed or not with low- or high-grade intraepithelial lesions of cervix. Case-control analyses were carried out by logistic regression adjusted for several socio-demographic, sexual lifestyle, and clinical data. The homozygous genotype of the rs3761548 variants (A/A) (related to decreased FOXP3 expression) may exert a protective role against HPV infection in women (ORAj: 0.60; 95% CI 0.36-0.99; p = 0.049) and was an independent predictor of protection against HSIL development (ORAdj: 0.28; 95% CI 0.11-0.68; p = 0.006). In addition, the homozygous genotype (G/G) of the rs2232365 variants (related to increased FOXP3 expression) was independently associated with the HPV infection (ORAdj: 2.10; 95% CI 1.06-4.15; p = 0.033). Haplotype analysis revealed no significant associations in our study. Our results reveal the significant and independent associations between FOXP3 genetic variants and susceptibility to HPV infection and SIL diagnosis and their role as biomarkers of HPV infection and cervical lesion management.

Expectant Management of High-Grade Anal Dysplasia in People with HIV: Long-term Data.

Both ablation and expectant management of high-grade squamous intraepithelial lesions have been proposed. Expectant management would be reasonable if 1) the rate of high-grade squamous epithelial lesion progression to anal squamous cell carcinoma were low, and 2) anal squamous cell carcinoma arising under surveillance had a better prognosis than anal squamous cell carcinoma presenting without an identified precursor. This study aims to quantify aspects of high-grade squamous epithelial lesion/anal squamous cell carcinoma clinical evolution in a surgical practice. This is a retrospective cohort study. This study was performed in 1 colorectal surgeon's practice over a 20-year period. Consecutive patients with high-grade squamous intraepithelial lesion and anal squamous cell carcinoma were included. We looked at the rate and timing of progression to anal squamous cell carcinoma, and the stage, treatment, and outcome of anal squamous cell carcinoma. We reviewed a comparison group of HIV-positive patients presenting de novo with anal squamous cell carcinoma (no prior history of high-grade squamous intraepithelial lesion). With consideration of only HIV-positive patients, 341 patients had a mean 5.6 years follow-up from high-grade squamous intraepithelial lesion diagnosis to the most recent documented anal examination. Twenty-four of these surveillance patients developed anal squamous cell carcinoma, yielding a progression rate of 1.3% per patient-year. Mean follow-up was 7.3 years from the initial cancer diagnosis to the most recent contact. Forty-seven patients who presented de novo with anal squamous cell carcinoma developed 74 lesions, with a mean follow-up of 5.7 years after initial diagnosis. This de novo group had higher anal squamous cell carcinoma-specific mortality (3% per patient-year vs 0.05%). Our study did not show a significantly higher rate of high stage (stage III or IV) at anal squamous cell carcinoma diagnosis in the de novo group in comparison with the surveillance group (25.5% vs 8.3% (p = 0.09)). This study was retrospective in nature and had a predominately male population. The progression of untreated high-grade squamous intraepithelial lesion to anal squamous cell carcinoma approximates 1% per patient-year. Anal squamous cell carcinoma developing under surveillance tends to be of an earlier stage and to require fewer major interventions than anal squamous cell carcinoma presenting de novo. Cancer-specific mortality was lower for malignancies that developed under surveillance. We suggest that expectant management of patients with high-grade squamous intraepithelial lesion is a rational strategy for preventing anal cancer morbidity. See Video Abstract at http://links.lww.com/DCR/A699.

The pathological outcome of ThinPrep Pap tests diagnosed as glandular cell abnormalities alone versus combined glandular and squamous abnormalities.

Although the incidence of glandular cell abnormalities (GCA) on cervical cytology is low, the clinical and histologic findings are often significant. A combined diagnosis of squamous intraepithelial lesion (SIL) and GCA indicates concern for either two distinct lesions or single entity. The goal of this study is to evaluate the outcome of the diagnosis of GCA alone or in combination with squamous abnormality (SqA). From January 2012-June 2017, our laboratory processed 162 088 ThinPrep Pap tests. 998 (0.61%) cases were reported as GCA. Histologic follow-up was available in 569 cases after excluding adenocarcinoma, NOS and atypical endometrial cells. HPV results were available in 429 (67.2%) cases. The surgical follow-up on 271 cases with GCA alone diagnosis revealed negative/benign lesions in 183 (67.5%) cases, glandular lesions in 40 (14.8%) cases; SqA in 47 (17.3%) cases; combined in 1 (0.4%) case. Surgical follow-up on 298 cases with dual interpretation revealed negative/benign lesions in 108 (36.2%) cases, SqA in 159 (53.4%) cases, GCA in 21 (7.0%) cases and only 10 (3.4%) cases were combined lesions. The mean age was 44 ±13.36 years. The overall hrHPV-positive rate was 36.2%. Endometrial carcinoma was most common abnormality in patients >65 years (71.4%) especially with hrHPV-negative results. CIN 1-3 was the most common finding in patients <30 years (50%). A cytological diagnosis of GCA has a higher risk of glandular abnormality on surgical follow-up especially in the older and hrHPV-negative group (P < .0001) while a combined diagnosis has a higher risk of a squamous lesion especially in <30 years (P < .0001). The combination of cytology, hrHPV-status and patient age can significantly aid in the stratification of the patient into high risk for glandular/squamous lesions which results in appropriate management.

Routine Use of Adjunctive p16 Immunohistochemistry Improves Diagnostic Agreement of Cervical Biopsy Interpretation: Results From the CERTAIN Study.

The diagnosis of squamous intraepithelial lesions in cervical tissue specimens is subject to substantial variability. Adjunctive immunohistochemical (IHC) staining for p16 has been shown to add objective biomarker information to morphologic interpretation of hematoxylin and eosin (H&E)-stained tissues. In the CERvical Tissue AdjunctIve aNalysis (CERTAIN) study, we systematically analyzed the impact of adjunctive p16 IHC on the accuracy (agreement with reference pathology results) of diagnosing cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) in the United States. Eleven hundred cervical biopsies were divided into 4 sets of 275 cases by stratified randomization. All H&E slides from each set were interpreted by 17 to 18 individual surgical pathologists, for a total of 19,250 reads by 70 surgical pathologists. After a wash-out period and blinding to original results, cases were re-read by the same pathologists using H&E+p16-stained slides. Using expert consensus diagnoses on H&E+p16 as reference, adjunctive p16 IHC use significantly improved diagnostic agreement of surgical pathologists by 4.7% (95% confidence interval [CI], 3.9, 5.4; P<0.0001). This improvement was driven by an increase of 11.5% (95% CI, 9.3, 13.5; P<0.0001) in sensitivity and an increase of 3.0% (95% CI, 2.2, 3.7; P<0.0001) in specificity. Diagnostic performance was significantly increased as well when expert consensus diagnoses established on H&E only was used as reference. Furthermore, interobserver reliability improved significantly from moderate (H&E: κ=0.58) to substantial (H&E+p16: κ=0.73; P<0.0001). Adjunctive use of p16 IHC provides more accurate and reproducible diagnostic results in the interpretation of cervical biopsies, ensuring that more patients are treated correctly without treating more patients.

Диагностика плоскоклеточных интраэпителиальных поражений и рака шейки матки на основании количественной оценки экспрессии микроРНК.

Диагностика плоскоклеточных интраэпителиальных поражений и рака шейки матки на основании количественной оценки экспрессии микроРНК.

HPV-associated disease of the anal canal: A pathology primer

Anal cancer is a rare disease. Screening for it in high-risk populations is based on the model borrowed from cervical cancer screening with cytology and high-resolution anoscopy-guided biopsy. Squamous cell carcinoma of the anus is associated with oncogenic HPVs, particularly type 16. Squamous intraepithelial lesions (SIL) are graded on both anal cytology and histology using 2 tiers. Low-grade SIL is reflective of a productive HPV infection; high-grade SIL is the potential precancer. High-risk HPV testing may not be an efficient screening or triage tool given the high prevalence of the virus in populations targeted for anal cancer screening. However, genotyping for HPV 16 may prove useful. On biopsy, p16 immunostaining is used to adjudicate equivocal diagnoses on routine H&E tissue sections; a positive p16 immunostain supports a diagnosis of high-grade SIL.

Prevalence of Primary HPV in Djibouti: Feasibility of Screening for Early Diagnosis of Squamous Intraepithelial Lesions.

In many African Sub-Saharan countries, human papilloma virus (HPV) prevalence data are not available. The current study estimated the prevalence of HPV virus in the female population of Djibouti. Approximately 1000 asymptomatic women 16 to 64 years old were enrolled from 3 of the main health structures of Djibouti in 2014 and 2015; 998 cervical samples were tested for HPV-DNA of high risk types, 499 during the first year, and 499 during the second. Positive samples were typed with an HPV genotyping kit. The women were an average age of 38.8 years (SD, 10.2); 54 women tested positive for HPV (prevalence rate, 5.4% [95% confidence interval, 4.0-6.8]). The highest prevalence was observed among the women younger than 35 years. HPV66 was the most prevalent (15.4% of the infections), followed by HPV31 and HPV52 (10.8% both) and HPV16 (9.2%). All 54 women who tested HPV-positive underwent a Pap test, which was positive in 8 cases (14.8%): 2 high-grade squamous intraepithelial lesion (HSIL) and 6 low-grade (LSIL). The HPV prevalence shows a curve by age similar to that of other African countries. The proportion of HPV16 is among the lowest ever seen in similar studies. The findings suggest to Djibouti the choice of a strategy of screening that includes forms of cytological triage, thus limiting recourse to colposcopy.

Precancerous squamous intraepithelial lesions by human papillomavirus infection and p53 R72P polymorphism in Mexican women

The aim was to determine the association between R72P polymorphism of p53 gene and the risk of developing squamous intraepithelial cervical lesions in HPV-16 and /or 18 infected women. Two groups of women were included in this study: 74 patients HPV-16 and /or 18 positive with a cytological and colposcopy diagnosis of squamous intraepithelial lesion and a group of unrelated 130 healthy blood-donors. The viral genotype, allele and genotype of the polymorphism frequencies were determined by PCR approached. The results were analyzed with the statistical programs DeFinetti and STAT intercooled v11.1. Patients with high-grade squamous intrahepitelial lesions (HG-SIL) were infected mainly by HPV-16 (60.72%) compared to low-grade lesions (LG-SIL) (39.28%) (OR 3.14; p= 0.037), with HPV-18 genotype 68.96% of LG-SIL and 31.04% were HG-SIL (OR=0.24, p=0.006). HG-SIL were more common in patients carrying both viral genotypes (70.59% vs 29.41%) (OR 2.8, p = 0.008). A statistically significant association was observed between the genotype R/R and HG-SIL (OR=11.25, IC 3.8-33.29, p= 0.000) compared to those with LG-SIL. The P/R genotype was significantly more frequent in patients LG-SIL, compared to HG-SIL (OR=0.27, p=0.00). In conclusion patients with the R/R genotype showed more susceptibility to HPV-16 infection and they have almost 12 times more risk probability of HG-SIL compared to women having the heterozygous genotype and HPV-18.