Intraepithelial Squamous Cell Carcinoma Research Articles

CD4+ and CD8+ cell populations in HIV-positive women with cervical squamous intra-epithelial lesions and squamous cell carcinoma

IntroductionThis study aimed to analyse cervical lymphocytic populations in HIV+ and HIV− patients and correlate different cervical lesions with HIV viral load and presence of high-risk HPV types. Material and methodsA total of 132 histological specimens from 40 HIV+ and 72 HIV− patients were evaluated for CD4+ and CD8+ T cell distribution, presence of high-risk HPV types, peripheral blood HIV viral load and CD4+/CD8+ ratio. ResultsHigh-grade squamous intraepithelial lesions (HSIL) and squamous cell carcinoma (SCC) from HIV+ patients had lower CD4+ T cell scores compared with HIV− patients. In all lesion groups, HIV+ patients presented higher epithelial and stromal CD8+ T cell scores. HIV viral load was more often detectable in patients with SCC than in those with low-grade squamous intraepithelial lesion (LSIL) (p = 0.0409). HSIL HIV+ patients had lower circulating CD4+ T cell counts (p = 0.0434) and CD4+/CD8+ ratio (p = 0.0378) compared with LSIL HIV+ patients. High-risk HPV types other than 16 and 18/45 were more prevalent in the HIV+ group. DiscussionThese results support an imbalance between cervical CD4+ and CD8+ T lymphocytes of HIV+ patients with SIL and SCC, with increased CD8+ infiltrate density with lesion severity, even in patients with immune system recovery under cART.

Immunohistochemical expression of p16INK4A in the lesions of uterine cervix

Background: Cervical cancer is the major cause of cancer deaths among women. Globally, around 5,70,000 new cases of cervical cancer and 3,11,000 deaths occurred in the year 2018. In India, Cervical cancer is a leading cause of cancer related mortality among women and the number of deaths is 60,000 per year among 97,000 diagnosed patients, especially those from lower socioeconomic group. Human Papilloma Virus (HPV) plays a crucial role in causing cervical dysplasia. This is done by upregulating p16INK4A, a cyclin dependent kinase inhibitor through interaction with cellular regulatory proteins. Hence p16INK4A can be used as a biomarker, since it is directly related variable for the presence of HPV. This study was conducted to evaluate the expression of p16INK4A in benign, premalignant and malignant cervical lesions and to assess its utility in diagnosing and grading cervical lesions.
 Methods: A total of 80 cervical specimens categorized histopathologically into nonspecific cervicitis, low grade squamous intraepithelial neoplasia (LSIL), high grade squamous intraepithelial neoplasia (HSIL) and squamous cell carcinoma cervix were included in this prospective study of one-year duration. Immunohistochemical study of p16INK4A were interpreted qualitatively and semi-quantitatively by Allred scoring system (0 to 8 points) which measures the proportion of stained cells and intensity of staining of cells. The collected data were statistically analyzed by ANOVA and chi square test.
 Result: Qualitative method showed absence of p16INK4A expression in all nonspecific cervicitis. 16.7% (2/12) LSIL, 100% (12/12) HSIL and 100% (28/28) squamous cell carcinoma cases showed p16INK4A positivity. Allred scoring of p16INK4A showed 66% (8/12) HSIL and 85.7% (24/28) squamous cell carcinoma cases with score 3 positivity. Hence high-grade lesions showed higher expression of this marker.
 Conclusion: IHC expression of p16INK4A showed increasing degree of expression from benign to premalignant and malignant lesions suggesting its diagnostic and prognostic value in the cervical cancer management

The expression of p16 and galectin-3 in cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma (SCC) uterine cervix

Cervical cancer is the most prevalent cancer among women in India. The main cause of cervical cancer is persistent human papilloma viral (HPV) infection. HPV inactivates the pRb tumour suppressor protein; thus p16 expression, which is controlled by a negative feedback mechanism, is relatively increased. Galectin-3 is directly and indirectly connected to cancer cell activity and contributes to oncogenesis, angiogenesis, cancer progression and metastasis. Thus, the aim of this study was to study the expression of p16 and galectin-3 in Cervical Intraepithelial Neoplasia (CIN) and Squamous Cell Carcinoma (SCC) and to correlate p16 and galectin-3 expression. On hundred and eighteen newly-diagnosed untreated cases of CIN and SCC of uterine cervix were included in the study. Expression of p16 and galectin 3 was more pronounced in invasive SCC and High-grade Intraepithelial Lesion (HSIL), as compared to Low-grade Intraepithelial Lesion (LSIL).Thus, it may be used in clinical setting to monitor cervical lesions and to predict their progression. Impact statement What is already known on this subject? p16 overexpression is a surrogate biomarker of HPV infection and useful in evaluating HPV-associated squamous and glandular neoplasia of the lower gynaecologic tract. Increased galectin‐3 expression is seen in SCC cervical, with less consistent results in CIN. What do the results of this study add? The results of our study adds to the growing literature that p16 and galectin-3 expression have direct statistically significant correlation with a degree of dysplasia and SCC cervix. Expression of p16 and galectin-3 was more pronounced in invasive SCC and high-grade intraepithelial lesion (HSIL), as compared to low-grade intraepithelial lesion (LSIL). What are the implications of these findings for clinical practice and/or further research? This correction of p16 and galectin-3 expression with degree of dysplasia and SCC cervix can be used for screening and early detection of cervical lesions and thus aid their early treatment and increased survival.

Classification of adeno carcinoma, high squamous intraephithelial lesion, and squamous cell carcinoma in Pap smear images based on extreme learning machine

ABSTRACT Cervical cancer is a malignant tumour that attacks the female genital area originating from epithelial metaplasia in the squamous protocol junction area. One method of diagnosis of cervical cancer is to do a Pap smear examination by taking a cervical cell smear from the woman’s cervix and observing its cell development. However, examination of cervical cancer from Pap smear results usually takes a long time. This is because medical practitioners still rely on visual observations in the analysis of the results of Pap smear so that the results are subjective. Therefore, we need a programme that can help the classification process in establishing a diagnosis of cervical cancer with high accuracy results. In this study, a cervical cancer classification program was developed using a combination of the Grey Level Co-occurrence Matrix (GLCM) and Extreme Learning Machine (ELM) methods. There are three classes of cervical cell images classified, namely adenocarcinoma, High Squamous Intraepithelial Lesion (HSIL) and Squamous Cell Carcinoma (SCC). From the results of the training program obtained an accuracy 100% and from the testing program obtained an accuracy of 80%.

Coinfection of High-Risk Human Papillomavirus and Lower Genital Tract Pathogens in the Development of High-Grade Cervical Lesions.

Purpose This study investigated the infection status and relationship between other common lower genital tract infectious pathogens and high-risk human papillomavirus (HR-HPV) in the high-grade cervical lesions. Methods Overall, 882 patients were enrolled in this retrospective study, of which 339 patients (≥HSIL group) were confirmed with high-grade squamous intraepithelial lesions (HSIL) or cervical squamous cell carcinoma (SCC), while 543 patients (≤LSIL group) were diagnosed with low-grade squamous intraepithelial lesions (LSIL) or normal cervical pathology diagnosis. Cervical swab specimens were tested for HPV, pathogenic bacteria (PB), U. urealyticum (UU), M. hominis (MH), and C. trachomatis (CT) in both groups. Results The infection rates of HR-HPV, PB, UU (at high density), and CT were higher in the ≥HSIL group than in the ≤LSIL group (P < 0.001); however, higher infection rates with MH were not observed (P > 0.05). PB, UU, and CT were associated with HR-HPV infection (P < 0.001). The PB and UU infection rates in the ≥HSIL group were significantly different from those in the ≤LSIL group, regardless of whether there was an HR-HPV infection at the same time (P < 0.05). However, this was not the case for the CT (P > 0.05). Furthermore, 259 pathogenic bacterial strains were detected in 882 cases. The difference in the distribution of pathogenic bacterial flora in the different grades of cervical lesions had no statistical significance, which was prioritized over Escherichia coli (P > 0.05). Conclusion PB, UU, and CT infection is associated with susceptibility to HR-HPV, HR-HPV coinfection with these pathogens might increase the risk of high-grade cervical lesions, and PB and UU might be independent risk factors for cervical lesions.

Significant decrease of a master regulator of genes (REST/NRSF) in high-grade squamous intraepithelial lesion and cervical cancer

BackgroundThe repressor element 1-silencing transcription factor (REST) is a regulator of gene expression, and the Ras association domain family member 1 A (RASSF1A) is an important tumor suppressor gene involved in cancer development. Although extensive characterization of the roles of REST and RASSF1A in cancer development have been reported in cellular models, the link between them and their possible role in the development of squamous intraepithelial lesions (SIL) and squamous cell carcinoma (SCC) of the cervix have not been explored. The aim of this study was to evaluate the expression of REST and RASSF1A in cervical cytological and histological samples from patients diagnosed with SIL or SCC and in CC-derived cell lines. MethodsWe analyzed the expression of REST and RASSF1A by immunocyto/histochemistry in cervical samples from patients (n = 271) and in cancer cell lines. Data analyses were performed using the Kruskal–Wallis test and generalized linear models. ResultsWe identified binding sites for REST in RASSF1A and observed a significant reduction in REST and RASSF1A nuclear expression in samples from patients with high-grade SIL (HSIL) and SCC. For REST, we observed an average decrease of 334 and 423 r.u.d. for HSIL (n = 21) and SCC (n = 18) compared with non-LSIL (n = 72), whereas for RASSF1A, this decrease was 126 and 217 r.u.d., respectively (p < 0.001). ConclusionOur results provide evidence of the altered expression of REST and RASSF1A in SIL and SCC, with a significant decrease in HSIL, SCC, and SCC-derived cell lines; findings that can contribute to the diagnosis, prognosis, and post-treatment follow-up of patients diagnosed with SIL or SCC.

Diagnostic spectro-cytology revealing differential recognition of cervical cancer lesions by label-free surface enhanced Raman fingerprints and chemometrics

Herein we have stepped-up on a strategic spectroscopic modality by utilizing label free ultrasensitive surface enhanced Raman scattering (SERS) technique to generate a differential spectral fingerprint for the prediction of normal (NRML), high-grade intraepithelial lesion (HSIL) and cervical squamous cell carcinoma (CSCC) from exfoliated cell samples of cervix. Three different approaches i.e. single-cell, cell-pellet and extracted DNA from oncology clinic as confirmed by Pap test and HPV PCR were employed. Gold nanoparticles as the SERS substrate favored the increment of Raman intensity exhibited signature identity for Amide III/Nucleobases and carotenoid/glycogen respectively for establishing the empirical discrimination. Moreover, all the spectral invention was subjected to chemometrics including Support Vector Machine (SVM) which furnished an average diagnostic accuracy of 94%, 74% and 92% of the three grades. Combined SERS read-out and machine learning technique in field trial promises its potential to reduce the incidence in low resource countries.

HPV16 induces penile intraepithelial neoplasia and squamous cell carcinoma in transgenic mice: first mouse model for HPV‐related penile cancer

Penile cancer is an under-studied disease that occurs more commonly in developing countries and 30-50% of cases show high-risk human papillomavirus (HPV) infection. Therapeutic advances are slow, largely due to the absence of animal models for translational research. Here, we report the first mouse model for HPV-related penile cancer. Ten-week-old mice expressing all the HPV16 early genes under control of the cytokeratin 14 (Krt14) gene promoter and matched wild-type controls were exposed topically to dimethylbenz(a)anthracene (DMBA) or vehicle for 16 weeks. At 30 weeks of age, mice were sacrificed for histological analysis. Expression of Ki67, cytokeratin 14, and of the HPV16 oncogenes E6 and E7 was confirmed using immunohistochemistry and quantitative PCR, respectively. HPV16-transgenic mice developed intraepithelial lesions including condylomas and penile intraepithelial neoplasia (PeIN). Lesions expressed cytokeratin 14 and the HPV16 oncogenes E6 and E7 and showed deregulated cell proliferation, demonstrated by Ki67-positive supra-basal cells. HPV16-transgenic mice exposed to DMBA showed increased PeIN incidence and squamous cell carcinoma. Malignant lesions showed varied histological features closely resembling those of HPV-associated human penile cancers. Wild-type mice showed no malignant or pre-malignant lesions even when exposed to DMBA. These observations provide the first experimental evidence to support the etiological role of HPV16 in penile carcinogenesis. Importantly, this is the first mouse model to recapitulate key steps of HPV-related penile carcinogenesis and to reproduce morphological and molecular features of human penile cancer, providing a unique in vivo tool for studying its biology and advancing basic and translational research. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

STAT1 expression and HPV16 viral load predict cervical lesion progression.

Cervical cancer is the fourth leading cause of cancer-associated mortality worldwide. However, its underlying molecular mechanisms are unclear. It is important to explore these mechanisms in order to identify novel diagnostic and prognostic biomarkers. The present study determined the association between STAT1 and human papillomavirus (HPV)16 in cervical lesions. STAT1 expression was detected by immunohistochemistry. Quantitative PCR was used to detect HPV16 viral load and STAT1 expression in cervical lesions. The potential associations among STAT1 expression, HPV16 viral load and the severity of cervical lesions in patients were analyzed using receiver operating characteristic (ROC) curves. The Cancer Genome Atlas database was used to analyze STAT1 expression and survival. High STAT1 expression was observed in 10.71 (3/28), 41.18 (14/34), 53.06 (26/49) and 90.00% (27/30) of normal tissue, low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL) and cervical squamous cell carcinoma samples, respectively. The HPV16 copy number gradually increased with the progression of cervical lesions, with the highest copy number observed in cervical cancer samples. In addition, STAT1 expression was positively correlated with HPV16 viral load. Furthermore, ROC curve analysis demonstrated that the combination of STAT1 expression and HPV16 viral load was able to differentiate between LSIL/HSIL and cervical cancer samples. Bioinformatics analysis revealed that STAT1 expression was associated with improved survival in cervical cancer. Additionally, STAT1 expression was positively associated with the progression of cervical lesions, and HPV16 viral load may affect STAT1 expression. Overall, these findings indicate that STAT1 may be an indicator of the status of cervical lesions.

Invasive conjunctival melanoma mimicking ocular surface squamous neoplasia: a case series

BackgroundConjunctival melanoma is the second most common conjunctival malignant tumour after squamous cell carcinoma, usually arising from primary acquired melanosis and less commonly from a conjunctival naevus or de novo....

High Risk Human Papilloma Virus Genotype Distribution in Cervical Intraepithelial and Invasive Carcinoma

Background: High-risk (HR) Human Papillomavirus (HPV) is an established cause of cervical cancer. HPV genotype detection is significant in preventing cervical cancers through targeted vaccination our study aimed to identify HRHPV16/18 and non 16/18 in cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma (SCC). Methods: A retrospective study was performed at Pathology Department, BMSI, JPMC, Karachi. About 96 cases of CIN and SCC were included. Analysis of HPV genotypes was performed by DNA extraction, PCR amplification and flow-through hybridization technique. The probes used had a cluster of 13 HRHPV into a group of 3 as HPV HR 1, 2 and 3. Chi square/ Fischer Exact test were applied to observe the association of morphological types of the lesion and expression of HPV genotypes. Results: HPV DNA positivity was 44% in our series. HPV HR 1 was observed in majority of cases (61.9%), followed by HPV 16 in 23.8%, HPV HR 3 in 9.5%, and HPV HR 2 in 4.7% cases respectively. The unique finding was absence of HPV 18 in the series. High grade lesions and invasive cancers showed positivity for HPV HR 1 and HPV 16, while low grade lesions were positive for HPV HR 1, 2 and 3 respectively. Conclusion: HPV HR1 are major causative agents for low and high grade intraepithelial and invasive SCC, followed by HPV 16. Absence of HPV 18 was the novel finding. Our results differ from studies within and outside the region, suggestive of diversified genetic makeup and impact of detection techniques on results.

The correlation of HPV16 and HPV18 with local vaginal immunity after the treatment of cervical intraepithelial neoplasia

BackgroundThis study aimed to investigate the correlation between the level of HPV16 and HPV18 in patients with cervical lesions and the local vaginal immunity after receiving treatment with different degrees of cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC).MethodsOne hundred and thirty-six patients with LSIL (grade 1 CIN or CIN 1), 263 patients with HSIL (grade 2 and 3 CIN or CIN 2 and 3), and 33 patients with CSCC pathologically confirmed between November 2012 and September 2016 were assigned to the test group and 100 healthy women in the same period were assigned to the control group. ELISA was used to determine the levels of SIgA, IgG, IL-2, and IL-10 and the IL-2/IL-10 ratio in vaginal lavage fluid in the test group (before treatment and 3, 6, and 12 months after treatment) and the control group, respectively. Gene chip technology was adopted to test the HPV infection in the test group (before treatment and 3, 6, and 12 months after treatment) and the control group, respectively.ResultsThe results showed that the levels of SIgA, IgG, and IL-10 were positively correlated with the degree of cervical lesions and IL-2/IL-10 was negatively correlated with the degree in all patients before treatment. The levels of SIgA, IgG, and IL-10 were positively correlated with the degree of cervical lesions and IL-2/IL-10 was negatively correlated with the degree in HPV16 and HPV18-infected patients before receiving the treatment.ConclusionsThe recovery after the treatment of HPV infection is time-dependent and the immune system of patients with CIN starts to recover in the 6th month after treatment, early intervention is not recommended. However, the immune system is approximately in a normal sate at 12 months after treatment, at which time the efficacy can be evaluated, and clinical intervention can be initiated if necessary. The level of local immune factors in the vagina can be monitored to determine the progression and prognosis of patients’ cervical lesions.

Comparative transcriptomic profiling in HPV-associated cervical carcinogenesis: Implication of MHC class II and immunoglobulin heavy chain genes

AimWe aimed to determine the biological processes and pathways involved in cervical carcinogenesis associated with high-risk human papillomavirus (HPV) infection. Materials and methodsTotal RNA was extracted from three formalin-fixed paraffin-embedded (FFPE) samples each of normal cervix, HPV-infected low-grade squamous intraepithelial lesion (LSIL), high-grade SIL (HSIL) and squamous cell carcinoma (SCC). Transcriptomic profiling by microarrays was conducted followed by downstream Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. ResultsWe examined the difference in GOs enriched for each transition stage from normal cervix to LSIL, HSIL, and SCC, and found 307 genes to be differentially expressed. In the transition from normal cervix to LSIL, the extracellular matrix (ECM) genes were significantly downregulated. The MHC class II genes were significantly upregulated in the LSIL to HSIL transition. In the final transition from HSIL to SCC, the immunoglobulin heavy locus genes were significantly upregulated and the ECM pathway was implicated. ConclusionDeregulation of the immune-related genes including MHC II and immunoglobulin heavy chain genes were involved in the transitions from LSIL to HSIL and SCC, suggesting immune escape from host anti-tumour response. The extracellular matrix plays an important role during the early and late stages of cervical carcinogenesis.

Comparison of papanicolaou smear and human papillomavirus (HPV) test as cervical screening tools: can we rely on HPV test alone as a screening method? An 11-year retrospective experience at a single institution.

BackgroundThe decrease in incidence of cervical dysplasia and carcinoma has not been as dramatic as expected with the development of improved research tools and test methods. The human papillomavirus (HPV) test alone has been suggested for screening in some countries. The National Cancer Screening Project in Korea has applied Papanicolaou smears (Pap smears) as the screening method for cervical dysplasia and carcinoma. We evaluated the value of Pap smear and HPV testing as diagnostic screening tools in a single institution.MethodsPatients co-tested with HPV test and Pap smear simultaneously or within one month of each other were included in this study. Patients with only punch biopsy results were excluded because of sampling errors. A total of 999 cases were included, and the collected reports encompassed results of smear cytology, HPV subtypes, and histologic examinations.ResultsSensitivity and specificity of detecting high-grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma (SCC) were higher for Pap smears than for HPV tests (sensitivity, 97.14%; specificity, 85.58% for Pap smears; sensitivity, 88.32%; specificity, 54.92% for HPV tests). HPV tests and Pap smears did not differ greatly in detection of low-grade squamous intraepithelial lesion (85.35% for HPV test, 80.31% for Pap smears). When atypical glandular cells were noted on Pap smears, the likelihood for histologic diagnosis of adenocarcinoma following Pap smear was higher than that of high-risk HPV test results (18.8 and 1.53, respectively).ConclusionsPap smears were more useful than HPV tests in the diagnosis of HSIL, SCC, and glandular lesions.

Clinicopathological Characteristics of Squamous Cell Carcinoma and High-grade Squamous Intraepithelial Lesions Involving Endocervical Polyps.

To investigate the clinicopathological characteristics of high-grade squamous intraepithelial lesions (HSILs) and squamous cell carcinomas (SCCs) involving endocervical polyps (ECPs). We collected the endocervical polypectomy cases and performed pathological examination and cytohistological correlation. During a period of 12 years, 21 (1.1%) HSILs and two (0.1%) SCCs involving ECPs were identified in 1,905 cases. Twelve (63.1%) of the 19 cases were cytohistologically concordant. In five HSILs and one SCC with polypectomy margin involvement, residual HSIL was identified in conization or hysterectomy specimens. Furthermore, in two HSIL patients and one SCC patient with negative polypectomy margins, residual HSILs were found in the conization specimens. The prevalence of HSIL and SCC involving ECP in our cohort was similar to the rates found in previous studies. The presence of residual HSIL in nonpolypoid cervical tissue regardless of the polypectomy margin involvement suggests that conization or hysterectomy is needed for diagnostic or treatment purposes.

Prevalence and Genotype Distribution of High-Risk Human Papillomavirus among Chinese Women in Sichuan Province.

The estimation of prevalence and genotype distribution of high-risk human papillomavirus (HR-HPV) is important in formulating strategies for the prevention and screening of cervical cancer. This study aimed to determine HR-HPV prevalence and genotype distribution among Chinese women living in Sichuan Province. A total of 3,089 women were recruited from the Third People's Hospital of Chengdu in Sichuan Province. HR-HPV genotyping was assessed using real-time quantitative polymerase chain reaction. Up to 720 women (23.3%) were HR-HPV positive. A total of 81.1% (584/720) of women had a single HR-HPV genotype, and 18.9% (136/720) had multiple genotypes. The most frequently detected HPV genotype was HPV52, followed by HPV58, HPV16, and HPV51. Age subgroup analysis showed 2 peaks for the frequencies of HPV infections, one for the group of women under 29 years old, and the other for the group of women over 50 years old. Among the women for whom cytology results were available, HPV16 was the most commonly detected genotype among women affected with high-grade squamous intraepithelial lesion (32.5%) and squamous cell carcinoma, followed by HPV58, HPV33, and HPV52. This is one of the largest studies to demonstrate HPV prevalence and genotype distribution among Chinese women in Sichuan. The prevalence and genotype distribution of HR-HPV was unique with higher frequencies of HPV52 and HPV58.

Minichromosome Maintenance Complex (MCM) Genes Profiling and MCM2 Protein Expression in Cervical Cancer Development.

Objective:Minichromosome maintenance complex (MCM) proteins are essential for the process of DNA replication and cell division. This study aimed to evaluate MCM genes expression profiles and MCM2 protein in HPV-associated cervical carcinogenesis. Methodology: MCM2, 4, 5 and 7 genes expression profiles were evaluated in three cervical tissue samples each of normal cervix, human papillomavirus (HPV)-infected low grade squamous intraepithelial lesion (LSIL), high grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma (SCC), using Human Transcriptome Array 2.0 and validated by nCounter® PanCancer Pathway NanoString Array. Immunohistochemical expression of MCM2 protein was semi-quantitatively assessed by histoscore in tissue microarrays containing 9 cases of normal cervix, 10 LSIL, 10 HSIL and 42 cases of SCC. Results: MCM2, 4, 5 and 7 genes expressions were upregulated with increasing fold change during the progression from LSIL to HSIL and the highest in SCC. MCM2 gene had the highest fold change in SCC compared to normal cervix. Immunohistochemically, MCM2 protein was localised in the nuclei of basal cells of normal cervical epithelium and dysplastic-neoplastic cells of CIN and SCC. There was a significant difference in MCM2 protein expression between the histological groups (P = 0.039), and histoscore was the highest in HSIL compared to normal cervix (P = 0.010). Conclusion:The upregulation of MCM genes expressions in cervical carcinogenesis reaffirms MCM as a proliferative marker in DNA replication pathway, whereby proliferation of dysplastic and cancer cells become increasingly dysregulated and uncontrolled. A strong expression of MCM2 protein in HSIL may aid as a concatenated screening tool in detecting pre-cancerous cervical lesions.

Incidence of cervical high-grade squamous intraepithelial lesions and squamous cell carcinoma in women with high-risk human papillomavirus and normal cervical cytology: A retrospective analysis of 1858 cases stratified by age and human papillomavirus genotype.

To retrospectively analyse the incidence of high-grade squamous intraepithelial lesions (HSILs) and squamous cell carcinoma (SCC) in women of different ages with high-risk (HR) human papillomavirus (HPV) but with normal cytology test results stratified by age and HPV genotype. In total, 1858 women with HR-HPV infection but with a normal smear who received a colposcopy and biopsy between 2015 and 2016 at our institution were included. The pathological results were retrospectively analysed after stratifying by age and HPV genotype. Among the 1858 cases, the HSIL% in women aged 21-29years (10.54%) was significantly different from that in women aged 40-49years (19.85%; P<0.05), whereas there was no significant difference in the HSIL% among women aged 21-29years and those in the other age groups (P>0.05). In total, 295 cases had single HPV16 infection. The HSIL% in patients with HPV16/18 infection was >15%, and the 40-49-year age group had the highest percentage at 48.48%. For other HR-HPV infections, the HSIL and SCC incidence rate was 10.41%, and there was no significant difference among the age groups; thus, women with other types of viral infections, regardless of age, should be referred to colposcopy. Although HPV16 is the HPV with the highest risk, other HR-HPV infections can also cause a high percentage of HSILs and SCC in women with normal cytology. Therefore, it is necessary to refer HR-HPV-infected women aged ≥21years for colposcopy in a timely manner to exclude potential cervical intraepithelial neoplasia and cervical cancer.

Clinicopathological features of intestinal mucosal lesions in AIDS patients and their relation with CD4+ T lymphocytes

Objective: To observe the histopathological features of different opportunistic infections and tumors of the intestinal mucosa in AIDS patients, and to explore the correlation between different lesions and CD4+ T lymphocyte levels. Methods: Colonic mucosal biopsy specimens of 263 patients with clinically diagnosed AIDS and abdominal pain, diarrhea, blood in the stool and other gastrointestinal symptoms were collected from Beijing Ditan Hospital from 2010 to 2018. There were 232 males and 31 females, with age range 10-81 (mean 40±13) years. HE staining, histochemical special staining, immunohistochemical staining, and in-situ hybridization were used to detect the expression of different opportunistic infection pathogens, tumors and CD4+ T lymphocytes. Peripheral blood was also taken for CD4+ T lymphocytes, CD8+ T lymphocytes, HIV viral load and routine indicators. Results: The cohort included 263 intestinal mucosal biopsy specimens. There were 175 cases (66.5%) of non-specific inflammation, and pathogens were detected in 41 cases (15.6%), including 20 cases(7.6%) of cytomegalovirus (CMV) infection, 12 cases (4.6%) of mycobacterial infection, eight cases (3.0%) of amoeba infestation, and one case (0.3%) of talaromycesmarneffei infection; there were also 41 (15.6%) neoplastic lesions including 25 cases (9.5%) of intraepithelial neoplasia, 10 cases (3.8%) of adenocarcinoma and squamous cell carcinoma, six cases (2.3%) of lymphoma; and six cases (2.3%) of ulcerative colitis. The peripheral blood CD4+T lymphocyte levels of patients with CMV, mycobacteria and talaromycesmarneffei were less than 200/μL; the peripheral blood CD4+ T lymphocyte level (P<0.01) and intestinal mucosa CD4+T lymphocytes (P<0.01) were all significantly lower than those in patients with non-specific inflammation. The peripheral red blood cells and hemoglobin levels of patients with CMV and mycobacterial infection (P<0.01), adenocarcinoma and squamous cell carcinoma (P<0.05) were significantly lower than those of non-specific inflammation patients. Conclusions: Pathologic examination of intestinal mucosa can identify specific infections and neoplastic lesions in AIDS patients; the most common lesions are non-specific inflammation, and CMV infection is the most common opportunistic infections; CMV, mycobacteria and talaromycesmarneffei infections are associated with decreased levels of CD4+ T lymphocytes in peripheral blood and intestinal mucosa; entamoeba histolytica infestation and non-HIV-related neoplastic lesions such as intraepithelial neoplasia, adenocarcinoma and squamous cell carcinoma are not associated with changes in AIDS immune function.

A Study of Pap Smears in HIV-Positive and HIV-Negative Women from a Tertiary Care Center in South India

Objectives: The aim of this work was to study the spectrum of epithelial abnormalities on Pap smears of HIV-positive women categorized as per the Bethesda System of Reporting Cervical Cytology, to correlate them with CD4 lymphocyte counts, and to compare them with the spectrum of abnormalities seen in a HIV-negative control group. Study Design and Methodology: The present study was a 6-year retrospective study conducted in the Department of Pathology at Kasturba Medical College, Mangalore, which included 150 Pap smears from HIV-positive and HIV-negative women, respectively. The Pap-stained slides of the cases were retrieved and studied. The data collected were tabulated and analyzed. A statistical study was performed using SPSS software. The χ² test was used to analyze the data and a p value < 0.05 was considered to be significant. Results: Pap smear abnormalities were twice as high in HIV-infected women (12%) as compared with HIV-negative women (6%; p = 0.006, RR = 2). Negative for intraepithelial lesion/malignancy was the most common finding (88%), which was further subdivided into inflammatory, atrophic smear, non-specific, candidiasis, and bacterial vaginitis groups. The percentage of epithelial abnormalities was 12%, including: atypical squamous cells of undetermined significance, 5.55%; atypical squamous cells, cannot exclude HSIL, 16.66%; low-grade squamous intraepithelial lesion, 5.55%; high-grade squamous intraepithelial lesion (HSIL), 61.11%, and squamous cell carcinoma, 11.11%. The highest incidence of intraepithelial lesions in HIV-positive females was in the age group of 34–49 years. CD4 cell counts fell in the range of 200–500 cells/mm³ in most of the HIV-positive patients (68.75%), but was not found to be statistically significant. Conclusion: Routine Pap smear examination is advocated in women with HIV as the prevalence of epithelial cell abnormalities was found to be 12%, which was twice as high as compared to the HIV-negative control group. Although there was no correlation of epithelial cell abnormalities with CD4 counts, a higher rate of the cases with epithelial abnormalities were observed to have CD4 cell counts of 200–500 cells/mm³.