HPV-associated Cervical Intraepithelial Neoplasia Research Articles

Цервикальная интраэпителиальная неоплазия. Клинический разбор

Cervical intraepithelial neoplasia (CIN) is the most relevant topic in cervicology due to the risk of progression to cervical cancer and its rejuvenation. The relationship of precancer with human papillomavirus (HPV) expands the range of examination in CIN. Modern approaches to the diagnosis and management of patients with CIN, including the possibilities of immunomorphology, are considered. A clinical examples of the management of a patients with HPV-associated CIN is given.

Analysis of the Results of Severe Intraepithelial Squamous Cell Lesions and Preinvasive Cervical Cancer Phototheranostics in Women of Reproductive Age.

(1) Purpose: To investigate the efficacy and safety of using PDT in the treatment of severe intraepithelial squamous lesions of the cervix and preinvasive cervical cancer associated with HPV in women of reproductive age. (2) Methods: The examination and treatment of 45 patients aged 22–49 years with morphologically confirmed HPV-associated cervical intraepithelial neoplasia of a severe degree (17 patients) and preinvasive cervical cancer (28 patients) were performed. All patients underwent PDT of the cervix using a chlorin e6 photosensitizer; after which, the affected areas of the cervix were evaluated using video and spectral fluorescence diagnostics. PDT effectiveness was assessed on the basis of colposcopy data, a cytological examination of exo- and endocervix and PAP test scrapings or the liquid cytology method, and polymerase chain reaction for HPV carriage 4 weeks after PDT, as well as on the basis of histological and immunohistochemical studies of biopsy materials 5 weeks after PDT. The expression levels of the Ki-67 and p16 markers in the affected areas of the cervix were also assessed. (3) Results. All patients included in the study tolerated the intravenous administration of the photosensitizer well, with no side effects or allergic reactions observed. In 88.2% of patients with CIN III/HSIL and in 85.7% of women with preinvasive cervical cancer, the effect of the treatment was noted after the first PDT procedure, while complete regression of the dysplasia foci was observed in 15 women (88.2%) with CIN III/HSIL and in 25 patients (89.3%) with preinvasive cervical cancer. Partial regression to the form of LSIL/CIN I was noted in two cases (11.8%) in the CIN III/HSIL group and in three cases (10.7%) in the group of patients with preinvasive cervical cancer. After PDT, a statistically significant decrease in the expression of the Ki-67 and p16 levels relative to the initial values was noted. (4) Conclusions. The results obtained indicate the high efficiency of PDT with intravenous administration of the chlorin photosensitizer for the treatment of intraepithelial lesions of the cervix with a selective effect on pathologically altered tissue. The use of this approach makes it possible to preserve the normal anatomical and functional characteristics of the cervix, which is especially important for maintaining the fertility of patients.

Manageable risk factors for progression of HPV-associated cervical intraepithelial neoplasia

Objective: to identify informative markers of the progression of cervical intraepithelial lesions of low degree.Materials and methods: the dynamics of the results of the cytological study of cervical epithelium, genotyping of human papilloma viruses of high carcinogenic risk (HPV) with an assessment of the viral load, an immunocytochemical study of the expression of protein p16 (p16INK4α), serum folic acid in 90 HPV-positive patients of reproductive age was analyzed. 43 of the 90 patients (47.8%) who made up group I had regression of the disease. Group II included 30 of 90 patients (33.3%) with disease persistence - no significant changes in the results of laboratory and instrumental research methods. Group III was 17 out of 90 patients (18.9%) with disease progression. Statistical processing of the results was carried out using parametric and non-parametric analysis methods using IBM SPSS Statistics 28.0.1.1 (developed by IBM Corporation), STATISTICA 13.5.0.17 (developed by StatSoft.Inc) and MedCalc 20.027. Results: factors that significantly distinguish patients with persistence or progression of low grade cervical intraepithelial lesions from women with regression of the disease are: earlier age of sexual onset, detection of atypical changes in low grade cervical epithelium, clinically significant HPV viral load, detection of p16INK4a protein expression, serum folic acid below 3.1 ng/ml. Conclusions: deficiency of serum folic acid in HPV of positive patients should be considered as a pathogenetically significant risk factor for the implementation of infection into the clinical form of the disease, which is confirmed by its correlation with the cytological detection of LSIL, progressive increase in the copy of HPV, and p16INKα expression. The patient management strategy, which provides a personalized assessment of the risk of progression of cervical intraepithelial lesions, expands the monitoring of patients with cervical neoplasias associated with HPV.

Immunological substantiation of complex therapy in patients with mild HPV-associated cervical intraepithelial neoplasia

Introduction. As is known, the development of invasive cervical cancer is preceded by cervical intraepithelial neoplasia of varying severity, which is a pathological process in which cells with varying degrees of atypia and impaired differentiation appear in the thickness of the stratified squamous epithelium of the cervix.Objective. To study the effect of complex therapy in patients with mild HPV-associated cervical intraepithelial neoplasia on the dynamics of local cytokine status and autoimmunity parameters.Materials and methods. The study included 86 patients aged 35 to 40 years with morphologically verified mild cervical intraepithelial neoplasia. The main group consisted of 52 patients who, along with radio wave destruction of the cervix, were prescribed an immunostimulating drug with antiviral activity “Groprinosin-Richter” 1000 mg 3 times a day for 10 days 10–14 days before destruction and similar 2 courses after 10–14 days after it. The comparison group included 34 patients who underwent only radio wave destruction of the cervix.Results. An analysis of the outcomes of low-grade squamous intraepithelial lesions after 6 months showed that in the main group, CIN I regression was observed in 92.3% of patients, persistence – in 7.7% of cases, while in the comparison group, CIN I regression was noted in 73,5% of cases, persistence – in 26.5% of patients.Conclusions. Conducting complex therapy, including radio wave destruction and the use of a drug with immunostimulating and antiviral activity “Groprinosin-Richter” in patients with low-grade HPV-associated cervical intraepithelial neoplasia, leads to the elimination of the initial imbalance of cytokines and normalization of autoantibody levels, helping to reduce the likelihood of HPV persistence and CIN progression to invasive cervical cancer uterus.

Изменение факторов иммунного ответа при терапии цервикальных интраэпителиальных неоплазий

Th e aim of the research. Assessment of changes in immune response factors during antiviral therapy of cervical intraepithelial neoplasia of severity grades I and II against the background of human papillomavirus. Material and methods. An outpatient examination of 232 female subjects of reproductive age was carried out. Among these, 172 women were with a histologically confi rmed diagnosis of mild to moderate cervical intraepithelial neoplasia (CIN I-II) associated with papillomavirus infection. During the work, each patient underwent cytological and colposcopic examination as well as real-time HPV typing with viral load evaluation. To establish the fi nal diagnosis, if necessary, a multifocal biopsy of the cervix was used. Within the framework of the designated goal, changes in the cervical zone were studied and analysed by means of assessing caspase-3, caspase-9, IFN-γ, IL-18. Results. As part of the study, changes in the caspase and cytokine profi le were analysed in HPV-associated cervical intraepithelial neoplasia of grades I-II, which substantiated the use of immune system correction for successful treatment of patients with mild to moderate dysplastic processes. Conclusion. The results obtained in the study make it possible to optimise management of patients with HPV-associated cervical intraepithelial neoplasia of severity degrees I-II.

Human papillomavirus-associated cervical intraepithelial neoplasia in the presence of iodine deficiency

Introduction. Cervical cancer holds one of the top positions in the oncological diseases ranking among the female population in the presence of iodine deficiency in the territory of the Republic of Bashkortostan. It's commonly believed that it is caused by the development of cervical intraepithelial neoplasia (CIN) associated with highly oncogenic strains of the human papillomavirus (HPV). The article pays special attention to the risk factors for the development of precancerous and cancerous diseases of the cervix and their timely treatment.The aim of the study was to improve the diagnosis and therapy of HPV-associated CIN in the presence of iodine deficiency in the Republic of Bashkortostan.Materials and methods. 256 women aged between 21 and 45 years with identified HPV-associated CIN I were enrolled in our study. The first stage of treatment known as preoperative was carried out in the outpatient setting. At stage 2, the patients were offered a radio-wave surgery treatment of the cervix.Results and discussion. The video colposcope analysis showed that the average time of epithelialization of the cervix after exposure to the destruction depended on the age and duration of the disease. For instance, complete epithelialization of the cervix in the group of patients aged between 21 to 38 years was reported in 72% of cases by Day 40, and in 62% of cases in the group of 39-45 years old on Day 40. The complete elimination of the virus was observed in 236 patients out of 256 cases (92%) 70 days after the end of therapy.Сonclusion. The study proves the effectiveness of the combination treatment of patients with HPV-associated CIN.

Vulvovaginitis and their correction in patients with cervical HPV-associated diseases in the light of the doctrine of pathomorphosis

Background. Biological pathomorphosis of the leading pathogens of the vaginal microecological system with the occurrence of vulvovaginitis in human papillomavirus (HPV)-associated cervical intraepithelial neoplasia (CIN) is a fundamental prerequisite for optimizing the complex treatment of this disease.
 Aim. Optimization of treatment of vulvovaginitis based on the study of the pathomorphism of their pathogens in patients with HPV-associated CIN.
 Materials and methods. A two-stage examination of 211 patients with HPV-associated CIN I was carried out from 2013 to 2020. To study the pathomorphosis of the disease, the patients were divided into 2 groups, the 1st group was examined in 20132016, the 2nd in 20172020. The study of microbiocenosis was carried out by RT-PCR using Femoflor-16 reagents. At the second stage, a study of the clinical efficacy of treatment of vulvovaginitis with the complex drug nifuratel 500 mg + nystatin 200 thousand IU (Macmiror Complex) in comparison with metronidazole 500 mg.
 Results and discussion. It was revealed that patients with HPV-associated CIN I over the last 8 years have a pathomorphosis of pathogens. In particular, the change in the dominance of anaerobic dysbiosis with the highest bacterial replication of Gardnerella vaginalis in association with Clostridium, Megasphaera spp. and Fusobacterium on the mixed nature of microflora, manifested in the form of vulvaginitis with the dominance of Atopobium vaginae in association with G. vaginalis, Ureaplasma (urealyticum + parvum) and the addition of the intestinal group Enterobacteriaceae spp. and Escherichia coli. The use of the complex drug nifuratel 500 mg + nystatin 200 thousand IU (Macmiror Complex) demonstrated a higher (4 times) clinical efficacy, a 12-fold decrease in the recurrence of the inflammatory process compared with metronidazole in the treatment of vulvovaginitis in patients with CIN I.
 Conclusions. 1. The structure of the cervico-vaginal microbiota in HPV-associated CIN I degree is characterized by dysbiotic disorders in 68.3% of cases. During the last 8 years, there was a pathomorphosis of the microecological status from the dominant anaerobic (in 74.2% of cases, =9.39 at p=0.001) to the dominant mixed (in 60.8% of cases, =8.54 at p=0.001 ) with the addition of the intestinal group Enterobacteriaceae spp. and E. coli in 60.8% of patients (=9.59 at p=0.001), which indicated a change in the dominant causative agents of vulvovaginitis in CIN I. 2. Comparative analysis of the clinical efficacy of complex drugs has demonstrated an increase in clinical efficacy when using the drug nifuratel 500 mg + nystatin 200 thousand IU by 4 times, a decrease in the recurrence of the inflammatory process by 12 times, compared with standard therapy with metronidazole, which allows us to recommend inclusion of the drug nifuratel 500 mg + nystatin 200 thousand IU in the therapy of vulvovaginitis in patients with CIN I.

Клинико-иммунологическое обоснование комплексного решения профилактики и терапии цервикальной интраэпителиальной неоплазии, ассоциированной с вирусом папилломы человека

A clinical and immunological analysis of the use of antiviral agent Inosine Pranobex (IP) as postoperative drug therapy in patients with cervical intraepithelial neoplasia (CIN) associated with human papillomavirus (HPV) is performed. It is known that IP has a high anti-relapse activity adapted to the mechanisms of HPV elimination (through the sequence of oncoproteins E5, E6 and E7, a decrease in the synthesis of interferons (IFNs) occurs and resistance of HPV-infected cells to IFN is formed). In this work, a number of statements justifying the priority of IP in the treatment of patients with CIN associated with HPV is covered, namely that IP induces trained immunity, differentiation of the Th1 subset of CD4+ T cells and proliferation of CD8+ T cells. Conclusion. Inosine Pranobex should be considered as the medication of choice for postoperative monotherapy in patients with HPV-associated CIN. Inosine Pranobex is characterized by mechanisms of action in both virus-infected cells and through the activation of innate and adaptive immune cells. Key words: CIN, human papillomavirus, inosine pranobex, clinical and immunological aspects, trained immunity

The Role of the Cervicovaginal and Gut Microbiome in Cervical Intraepithelial Neoplasia and Cervical Cancer.

The microbiome, which refers to the microbiota within a host and their collective genomes, has recently been demonstrated to play a critical role in cancer progression, metastasis, and therapeutic response. The microbiome is known to affect host immunity, but its influence on human papilloma virus (HPV) gynecologic malignancies remains limited and poorly understood. To date, studies have largely focused on the cervicovaginal microbiome; however, there is growing evidence that the gut microbiome may interact and substantially affect therapeutic response in gynecologic cancers. Importantly, new developments in microbiome sequencing and advanced bioinformatics technologies have enabled rapid advances in our understanding of the gut and local tumor microbiota. In this review, we examine the evidence supporting the role of the microbiome in HPV-associated cervical intraepithelial neoplasia (CIN) and cervical cancer, explore characteristics that influence and shape the host microbiota that impact HPV-driven carcinogenesis, and highlight potential approaches and considerations for future and ongoing research of the microbiome's effect on HPV-associated cancer.

Особенности консервативной иммунопротивовирусной терапии пациенток с ВПЧ-ассоциированными цервикальными интраэпителиальными неоплазиями I степени

Особенности консервативной иммунопротивовирусной терапии пациенток с ВПЧ-ассоциированными цервикальными интраэпителиальными неоплазиями I степени

The specific features of cervical intraepithelial neoplasia associated with persistent HPV infection

Aim. Of the study was to assess the clinical and laboratory features of cervical intraepithelial neoplasia (CIN) with persistent human papillomavirus infection and the development of prognostic criteria for persistence of HPV. Materials and methods. The prospective study included 63 patients with HPV-associated CIN. Assessment of persistence of HPV was based on detection of HPV when retesting 12 months. Depending on the results of retesting there were 2 groups: group 1A (main group, n=26), including patients with CIN and HPV persistence after treatment, mean age - 33.69±1.92 years; group 1B (comparison, n=37) - patients with CIN without HPV persistence after treatment, mean age - 34.43±2.09 years. Results. According to the results of the first HPV genotyping (before treatment) among patients of group 1A there was a predominance of two or more HPV types (34.6% vs 16.2% of patients of group 1B; p0.05). According to the results of the second genotyping (12 months after complex treatment) there was a 3.5-fold prevalence of patients with mono-infection against HPV co-infection in group 1A (p

Toll-like receptors: Important immune checkpoints in the regression of cervical intra-epithelial neoplasia 2.

Toll-like receptors (TLRs) are innate immune defenders thought to be critical for the clearance of human papillomavirus (HPV) infections hence preventing the development of HPV-associated high-grade cervical intra-epithelial neoplasia (CIN2 or 3), a potential cervical cancer precursor. However, the role of TLRs in the regression of established cervical lesions, such as CIN2, is hindered by a lack of prospective design studies. Using SYBR green real-time PCR assays, we have examined the gene expression of TLR2, TLR3, TLR7, TLR8 and TLR9, in cytobrush collected endocervical cells of 63 women diagnosed with CIN2 at study entry (baseline) and followed over a 3-year period. Wilcoxon rank-sum test was used to examine the association between TLR expression levels, measured at baseline, and CIN2 outcome (regression vs. persistence/progression) over time. HPV genotyping was performed using Roche Linear Array Assay detecting 37 HPV types. Women with CIN2 regression showed significantly higher baseline levels of TLR2 (p = 0.006) and TLR7 (p = 0.007), as well as a non-significant trend for a higher TLR8 expression (p = 0.053) compared to women with CIN2 persistence/progression. Six women with CIN2 regression, who presented with an HR-HPV DNA-negative CIN2 lesion at study entry, had significantly higher baseline levels of TLR2 (p = 0.005), TLR7 (p = 0.013) and TLR8 (p = 0.012), compared to women with CIN2 persistence/progression, suggesting their role in clearance of HPV prior to clearance of the lesion. Our results confirm a key role of TLRs in regression of CIN2 and support the potential use of TLR-agonists for treatment of these lesions.

Effect of inosine pranobex on p16, Ki-67 expression in patients with HPV-associated cervical intraepithelial neoplasia

The aim of the study - to determine the dynamics of expression of р16, Ki-67 in patients with HPV-associated cervical intraepithelial neoplasia (CIN) in the complex treatment with inosine pranobex. Materials and methods. The study included 62 patients with cervical HPV infection, the main group consisted of 47 patients with confirmed CIN 1 and CIN 2-3 associated to HPV high-risk, the comparison group - patients with latent HPV infection and 13 women of the control group. At the 2nd stage, a group of women with CIN 2-3 was divided into two groups: 2A (n=17) included patients who received excision treatment in combination with inosine pranobex; 2B group (n=9) patients after excision treatment (LEEP or LLETZ) without inosine pranobex. Traditional methods of examination of cervical pathology were used, including HPV genotyping, and dynamic immunocytochemical examination to determine p16, Ki-67. Results. Comparative analysis (n=75) allowed to establish the absence of differences in the expression of р16, Ki-67 and co-expression in HPV-associated CIN 1 relative to the comparison and control group. CIN 2-3 was characterized by a predominance of the levels of biomarkers in comparison with CIN 1 and latent infection (p

Combination treatment using cavitated Panavir solution in patients with HPV-associated cervical intraepithelial neoplasia

Combination treatment using cavitated Panavir solution in patients with HPV-associated cervical intraepithelial neoplasia

A polycomb-mediated epigenetic field defect precedes invasive cervical carcinoma.

Human papillomavirus (HPV)-associated cervical carcinoma is preceded by stages of cervical intra-epithelial neoplasia (CIN) that can variably progress to malignancy. Understanding the different molecular processes involved in the progression of pre-malignant CIN is critical to the development of improved predictive and interventional capabilities. We tested the role of regulators of transcription in both the development and the progression of HPV-associated CIN, performing the most comprehensive genomic survey to date of DNA methylation in HPV-associated cervical neoplasia, testing ~2 million loci throughout the human genome in biopsies from 78 HPV+ women, identifying changes starting in early CIN and maintained through carcinogenesis. We identified loci at which DNA methylation is consistently altered, beginning early in the course of neoplastic disease and progressing with disease advancement. While the loss of DNA methylation occurs mostly at intergenic regions, acquisition of DNA methylation is at sites involved in transcriptional regulation, with strong enrichment for targets of polycomb repression. Using an independent cohort from The Cancer Genome Atlas, we validated the loci with increased DNA methylation and found that these regulatory changes were associated with locally decreased gene expression. Secondary validation using immunohistochemistry showed that the progression of neoplasia was associated with increasing polycomb protein expression specifically in the cervical epithelium. We find that perturbations of genomic regulatory processes occur early and persist in cervical carcinoma. The results indicate a polycomb-mediated epigenetic field defect in cervical neoplasia that may represent a target for early, topical interventions using polycomb inhibitors.

'Drawing' a Molecular Portrait of CIN and Cervical Cancer: a Review of Genome-Wide Molecular Profiling Data.

In this review we summarize the results of studies employing high-throughput methods of profiling of HPV-associated cervical intraepithelial neoplasia (CIN) and squamous cell cervical cancers at key intracellular regulatory levels to demonstrate the unique identity of the landscape of molecular changes underlying this oncopathology, and to show how these changes are related to the 'natural history' of cervical cancer progression and the formation of clinically significant properties of tumors. A step-wise character of cervical cancer progression is a morphologically well-described fact and, as evidenced by genome-wide screenings, it is indeed the consistent change of the molecular profiles of HPV-infected epithelial cells through which they progressively acquire the phenotypic hallmarks of cancerous cells. In this sense, CIN/cervical cancer is a unique model for studying the driving forces and mechanisms of carcinogenesis. Recent research has allowed definition of the whole-genome spectrum of both random and regular molecular alterations, as well as changes either common to processes of carcinogenesis or specific for cervical cancer. Despite the existence of questions that are still to be investigated, these findings are of great value for the future development of approaches for the diagnostics and treatment of cervical neoplasms.

Systematic Review and Meta-Analysis of L1-VLP-Based Human Papillomavirus Vaccine Efficacy against Anogenital Pre-Cancer in Women with Evidence of Prior HPV Exposure

BackgroundIt is unclear whether L1-VLP-based human papillomavirus (HPV) vaccines are efficacious in reducing the likelihood of anogenital pre-cancer in women with evidence of prior vaccine-type HPV exposure. This study aims to determine whether the combined results of the vaccine trials published to date provide evidence of efficacy compared with control (hepatitis A vaccine/placebo).MethodsA systematic review and meta-analysis was conducted. Randomized-controlled trials (RCTs) were identified from MEDLINE, Embase, Web of Science, PubMed, Cochrane Central Register of Controlled Trials and references of identified studies. The bivalent vaccine containing HPV-16 and 18 VLPs from GlaxoSmithKline Biologicals (Rixenstart, Belgium), the quadrivalent vaccine containing HPV-6, 11, 16, and 18 VLPs from Merck & Co., Inc., (Whitehouse Station, NJ USA), and the HPV-16 monovalent vaccine from Merck Research Laboratories (West Point, PA USA) were evaluated.FindingsThree RCT reports and two post-trial cohort studies were eligible, comprising data from 13,482 women who were included in the vaccine studies but had evidence of HPV infection at study entry. Data on efficacy was synthesized using the Mantel-Haenszel weighted fixed-effect approach, or where there was heterogeneity between studies, the DerSimonian and Laird weighted random-effect approach. The mean odds ratio (OR) and 95% confidence interval (CI) for the association between Cervarix, Gardasil and HPV-16 monovalent vaccine and HPV-associated cervical intraepithelial neoplasia grade 3 or worse was 0·90 (95% CI: 0·56, 1·44). For the association between Gardasil and HPV-associated vulval/vaginal intraepithelial neoplasia grades 2–3, the overall OR and 95% CI was 2.25 (95% CI: 0·78, 6.50). Sample size and follow-up were limited.ConclusionsThere was no evidence that HPV vaccines are effective in preventing vaccine-type HPV associated pre-cancer in women with evidence of prior HPV exposure. Small effects of vaccination however cannot be excluded and a longer-term benefit in preventing re-infection remains possible.

Indoleamine 2,3-Dioxygenase Activity Contributes to Local Immune Suppression in the Skin Expressing Human Papillomavirus Oncoprotein E7

Chronic infection of anogenital epithelium with human papillomavirus (HPV) promotes development of cancer. Many pathogens evoke immunosuppressive mechanisms to enable persistent infection. We have previously shown that grafted skin expressing HPV16 E7 oncoprotein from a keratin-14 promoter (K14E7) is not rejected by a syngeneic, immunocompetent host. In this study we show that indoleamine 2, 3-dioxygenase (IDO) 1, an IFN-γ inducible immunoregulatory molecule, is more highly expressed by langerin−ve dermal dendritic cells from K14E7 skin than nontransgenic control skin. Furthermore, inhibiting IDO activity using 1-D/L-methyl tryptophan promotes K14E7 skin graft rejection. Increased IDO1 expression and activity in K14E7 skin requires IFN-γ and iNKT cells, both of which have been shown to negatively regulate T-cell effector function and suppress K14E7 graft rejection. Further, dendritic cells from K14E7 skin express higher level of IFN-γ receptor (IFN-γR) than dendritic cells from control skin. K14E7 transgenic skin recruits significantly higher number of dendritic cells, independent of IFN-γ and IFN-γR expression. Consistent with these observations in a murine model, we found higher expression of IDO1 and IFN-γ but not IDO2 in the cervical epithelium of patients with HPV-associated cervical intraepithelial neoplasia (CIN) 2/3. Our data support a hypothesis that induction of IDO1 in HPV infected skin contributes to evasion of host immunity.

P3.372 Systematic Review and Meta-Analysis of L1-VLP-based Human Papillomavirus Vaccine Efficacy Against Anogenital Pre-Cancer in Women with Evidence of Prior HPV Exposure

BackgroundIt is unclear whether L1-VLP-based human papillomavirus (HPV) vaccines are efficacious in preventing anogenital pre-cancer in women with prior vaccine-type HPV exposure. Participants in the phase III efficacy trials were...

Balance of apoptotic and anti-apoptotic marker and perforin granule release in squamous intraepithelial lesions. HIV infection leads to a decrease in perforin degranulation

Cell-mediated cytotoxicity plays an important role in the regulation to HPV-associated cervical intraepithelial neoplasia. HIV co-infection is related to poorer prognosis and more rapid clinical progression to cancer. We evaluated the presence of cervical inflammatory cells, apoptotic (Bax, Bcl-2, FasL, NOS2, perforin) markers and the degranulating expressing cell marker (CD107a) in low and high squamous intraepithelial lesions (LSIL and HSIL, respectively) from HIV-negative and -positive women. Higher percentage of cervical CD4+, CD8+ T cells and macrophage were observed in LSIL and HSIL groups when compared with control, especially in epithelium and basal layer of epithelium. However, progression from LSIL to HSIL did not change the frequency of inflammatory cells. HIV-infection lead to a reduction on cervical CD4+ T cell infiltration and an increased CD8+ T cell distribution in LSIL groups. A balance between pro- and anti-apoptotic protein expressions was verified. Bax-expressing cells were present in all groups and were rarely expressed in keratinocytes in the epithelium in LSIL and control groups, but notably decreased in HSIL group. However, its frequency was enhanced in the basal layer of the epithelium meanly in LSIL group. Bcl2-expressing cells in the epithelium and the stroma were enhanced in HSIL group when compared with LSIL group. HIV-infection did not interfere in both expressions NOS2 expression was located on keratinocytes in both LSIL and HSIL groups when compared with control group. There were few FasL cervical expressing cells in all groups. Indeed, perforin was identified in few cervical cells. However, CD107a, a surface marker for cellular degranulation was significantly higher in epithelium, basal layer of epithelium and stroma in LSIL and HSIL, respectively, when compared with control group. These results support that HIV infection may induce reduction on inflammatory cervical cell degranulation corroborating to carcinogenesis process. This is the first description on the role of HIV in downregulation of perforin degranulation in the cervical lesions and it might be related to carcinogenesis.