Human Papillomavirus Elimination Research Articles

Pharmacological correction of immunological disorders in perimenopausal women with recurrent epithelial cervical dysplasia associated with human papillomavirus infection

Despite the successes achieved in implementing screening programs and treating diseases caused by human papillomavirus (HPV) infection, the frequency of cervical intraepithelial neoplasia (CIN) of moderate and high grades associated with high-risk human papillomavirus (HR-HPV) remains between 9% to 21%. Vaginal dysbiosis and the development of immunodeficient states due to persistent HR-HPV infection require effective immunomodulatory and antiviral therapy before cervical surgery in perimenopausal women with recurrent CIN II.The objective: to evaluate the effectiveness of antiviral and immunomodulatory therapy by determining the state of vaginal biocenosis, immunological status and papillomavirus load of the cervical mucosa before surgical treatment in perimenopausal women with recurrent CIN II.Materials and methods. A prospective study was conducted on 98 women aged 40 to 55 years old, including 60 patients with morphologically verified recurrent CIN II associated with high-risk HPV, forming the main group. The control group comprised 38 women with negative HPV test results and without significant gynecological or somatic pathology. In the main group, a complex consisting of a blend of plant extracts of sod pike grass (Deschampsia caespitosa), ground cinquefoil grass (Calamagrostis epigeios), and echinacea purpurea grass (Echinaceae purpureae) was administered orally.Vaginal microbiota was assessed using Hey-Іson criteria, and immunological status was examined in patients using solid-phase enzyme-linked immunosorbent assay to determine IgG, IgM, IgA antibodies in serum and cervical mucus, levels of interleukin-1β (IL-1β), interferons alpha (IFN-α), gamma (IFN-γ), tumor necrosis factor alpha (TNF-α). Additionally, the DNA of high-risk HPV in cervical mucosa was quantitatively assessed using real-time PCR. The investigations were conducted before and after the applied therapy.Results. The investigation of vaginal content revealed the presence of bacterial vaginosis in 65.0% of patients in the main group, the frequency of which decreased by 2 times after treatment, with the number of women with an intermediate type of vaginal content increasing by 2.8 times (51.7%) and those with normal microbiota increasing by 2.5 times. Disruptions in cellular and humoral immunity systems were identified. After treatment, there was an increase in viral load in the significant «threshold» category (3–5 lg) by 1.25 times and in the «above threshold for progression» category (>5 lg) by 2.3 times, reflecting natural HPV clearance. No direct correlation was found between viral load activity and the degree of CIN or positive morphological changes regarding regression of cervical intraepithelial lesions.Conclusions. The use of a complex containing a blend of plant extracts of sod pike grass (Deschampsia caespitosa), ground cinquefoil grass (Calamagrostis epigeios), and echinacea purpurea grass (Echinacea purpureae) improves the state of vaginal biocenosis, indicators of cellular and humoral immunity, and promotes HPV elimination, it has adequate safety and tolerability, which determines the feasibility of its use in the complex treatment of cervical intraepithelial neoplasia at the preparatory stage before surgery and in the postoperative period to prevent complications and relapses.

Concomitant human papillomavirus (HPV) vaccination and screening for elimination of HPV and cervical cancer.

HPV vaccination with concomitant HPV-based screening of young women has been proposed for faster cervical cancer elimination. We describe the baseline results of a population-based trial of this strategy to reduce the incidence of HPV. All 89,547 women born 1994-1999 and resident in the capital region of Sweden were personally invited to concomitant HPV vaccination and HPV screening with 26,125 women (29.2%) enrolled between 2021-05-03 and 2022-12-31. Baseline HPV genotyping of cervical samples from the study participants finds, compared to pre-vaccination prevalences, a strong decline of HPV16 and 18 in birth cohorts previously offered vaccination, some decline for cross-protected HPV types but no decline for HPV types not targeted by vaccines. Our dynamic transmission modelling predicts that the trial could reduce the incidence of high-risk HPV infections among the 1994-1998 cohorts by 62-64% in 3 years. Baseline results are prevalences of HPV infection, validated transmission model projections, and power estimates for evaluating HPV incidence reductions at follow-up (+/-0.1% with 99.9% confidence). In conclusion, concomitant HPV vaccination and HPV screening appears to be a realistic option for faster cervical cancer elimination. Clinicaltrials.gov identifier: NCT04910802; EudraCT number: 2020-001169-34.

Scientific approaches toward improving cervical cancer elimination strategies.

At the 2023 EUROGIN workshop scientific basis for strategies to accelerate the elimination of cervical cancer and its causative agent, human papillomavirus (HPV) were reviewed. Although some countries have reached key performance indicators toward elimination (>90% of girls HPV vaccinated and >70% of women HPV screened), most are yet to reach these targets, implying a need for improved strategies. Gender-neutral vaccination, even with moderate vaccination coverage was highlighted as a strategy to achieve elimination more rapidly. It is more resilient against major disturbances in vaccination delivery, such as what happened during the coronavirus pandemic. Further, an analysis of ethical/legal issues indicated that female-restricted vaccination is problematic. Extended catch-up of vaccination with concomitant screening, and outreach to vulnerable groups were highlighted. Although birth cohorts with high coverage of HPV vaccination at school are protected against HPV, and HPVs have a very low reproductive rate in women above age 35, adult women below age 30 have inadequate direct protection. In addition to herd protection from gender-neutral vaccination, this group can be protected by offering concomitant catch-up HPV vaccination and HPV screening. Furthermore, hepatitis B vaccination experiences indicate that elimination cannot be achieved without prioritizing vulnerable/migrant populations. The long-lasting durability of vaccination-induced antibody responses suggests prolonged protection with HPV vaccines when adequately administrated. Finally, cost-effectiveness modelling suggests that high-coverage HPV vaccination in multiple population segments will be resource-saving due to reduced need for screening. In summary, the workshop found that strategically optimal deployment of vaccination will accelerate elimination of HPV and cervical cancer.

Фототераностика тяжелых дисплазий и преинвазивного рака шейки матки

Due to the high prevalence of pre-cancerous cervical diseases and cervical cancer, the search, pathogenetic reasoning and evaluation of the efficacy of new approaches to the diagnosis and treatment of these pathologies, including those aimed at fertility preservation, are extremely relevant. Objective. To study the clinical efficacy and safety of phototheranostics as a method of diagnosis and treatment of severe dysplasia and pre-invasive cervical cancer. Patients and methods. An open-label, retrospective-prospective, randomized, comparative, clinical trial involving 94 reproductive-aged patients with morphologically confirmed severe cervical intraepithelial neoplasia (CIN) and pre-invasive cervical cancer was conducted. All patients were divided into two groups: group 1 (comparison) included 49 patients who underwent cervical conization with curettage of the remaining cervical canal; group 2 (study) included 45 patients who underwent phototheranostics: photodynamic therapy (PDT) with simultaneous laser-induced fluorescence excitation. Results. After the first course of phototheranostics, most women in the study group had normal cytological results, which were observed 6, 9, and 12 months after treatment. In these periods, all patients who underwent phototheranostics had a normal colposcopic picture, while in the comparison group, some patients showed signs of cervical lesions. Morphological confirmation of the complete therapeutic effect was considered to be elimination of human papillomavirus (HPV) and normalization of the proliferative activity of the epithelial layer (assessed by the levels of Ki-67 and phosphohistone markers) during phototheranostics. Conclusion. The study demonstrated the high clinical efficacy of phototheranostics in the treatment of CIN and pre-invasive cervical cancer: 85–88% of women achieved the desired therapeutic effect after the first session of phototheranostics, and after the second session, all patients in the study group had complete regression of cervical mucosal lesions. In the study group, higher pregnancy rates and favourable outcomes in patients planning pregnancy confirmed that the use of PDT contributes to fertility preservation in women treated for CIN and pre-invasive cervical cancer, which is associated with the preservation of anatomo-functional characteristics of the cervix when using phototheranostics. Key words: PDT, HPV, photodynamic therapy, fluorescence diagnosis, cervical dysplasia, photosensitizers, pre-invasive cervical cancer, phototheranostics, pregnancy after PDT

Empowering Women's Health: Insights Into HPV Vaccination and the Prevention of Invasive Cervical Cancer.

This review article provides a comprehensive analysis of the role of human papillomavirus (HPV) vaccination in empowering women's health by preventing invasive cervical cancer. Cervical cancer remains a significant global health concern, with HPV infection identified as a primary causative factor. The review synthesizes current research findings, epidemiological data, and clinical outcomes to offer a nuanced understanding of the impact of HPV vaccination on cervical cancer prevention. The article explores the biology of HPV, emphasizing its association with cervical carcinogenesis and the development of precancerous lesions. It delves into the epidemiology of HPV infection, highlighting the global prevalence and the burden of cervical cancer, particularly in low-resource settings. The socio-economic factors influencing HPV transmission and cervical cancer incidence are also discussed. The focus of the review is on the efficacy and safety of HPV vaccines, including an examination of vaccine types, dosages, and long-term effectiveness. Insights into the immunological responses triggered by vaccination, as well as the duration of protection against HPV infection and associated cancers, are presented. Special attention is given to addressing myths and misconceptions surrounding HPV vaccination, aiming to enhance public awareness and acceptance. Additionally, the review discusses the impact of vaccination programs on population-wide HPV prevalence and the subsequent reduction in cervical cancer rates. It explores challenges related to vaccine accessibility, affordability, and coverage, especially in underserved populations. Strategies for improving vaccine uptake and ensuring equitable distribution are considered, with a focus on empowering women through education and healthcare access. Furthermore, the article touches upon emerging trends in HPV research, such as the development of next-generation vaccines, therapeutic interventions for existing infections, and the potential for global HPV elimination. The integration of HPV vaccination into comprehensive women's health programs is advocated, emphasizing the importance of a holistic approach to cervical cancer prevention. In conclusion, this review provides a multifaceted exploration of HPV vaccination as a pivotal tool in empowering women's health by preventing invasive cervical cancer. The synthesis of current knowledge underscores the need for continued research, education, and global collaboration to ensure the widespread success of HPV vaccination initiatives, ultimately contributing to the advancement of women's health worldwide.

Elimination of Human Papillomavirus and Cervical Pathological Microbiota with Photodynamic Therapy in Women from Mexico City with Cervical Intraepithelial Neoplasia I.

Cervical carcinoma (CC) is the second cause of cancer death in Mexican women. It starts with premalignant lesions known as Intraepithelial Cervical Neoplasia (CIN) that can develop due to infection by Human Papillomavirus (HPV) and other microorganisms. Current CIN therapy involves invasive methods that affect cervix integrity and fertility; we propose the use of photodynamic therapy (PDT) as a strategy with few side effects. In this work, the effectiveness of PDT for CIN I, HPV and pathogenic vaginal microbiota elimination in 29 women of Mexico City with CIN I, CIN I + HPV and HPV diagnosis was determined. After 6 months of PDT application, HPV infection was eliminated in 100% of the patients (P< 0.01), CIN I + HPV in 64.3% (P< 0.01) and CIN I in 57.2% (P> 0.05). PDT also eliminated pathogenic microorganisms: Chlamydia trachomatis in 81% of the women (P< 0.001) and Candida albicans in 80% (P< 0.05), without affecting normal microbiota since Lactobacillus iners was eliminated only in 5.8% of patients and the opportunistic Gardnerella vaginalis in 20%. These results show that PDT was highly effective in eradicating HPV and pathogenic microorganisms, suggesting that PDT is a promising therapy for cervical infections.

Противовирусный препарат аллоферон в лечении пациенток с цервикальными интраэпителиальными неоплазиями: обзорный анализ исследований

Aim: Analysis of the published results of scientific studies evaluating the effect of the antiviral drug alloferon on the reduction of viral load (VL) or the elimination of human papillomavirus (HPV) of high carcinogenic risk both in monotherapy of mild cervical intraepithelial neoplasia (CIN) and in complex treatment of severe CIN, as well as to evaluate the effect of the drug on the dynamics of clinical manifestations of CIN. Key points. Eight published domestic studies of the antiviral drug alloferon in the treatment of CIN of varying severity were analyzed. The selection of relevant publications in the scientific citation database PubMed and Google Scholar was carried out to assess the antiviral and immunomodulatory effect of this drug and a cumulative analysis of the results of the treatment of 646 patients with CIN of varying degrees (361 received alloferon, and 285 were in the control group). The average age is 31 years. VL was calculated per 100,000 human cells: less than 3 lg per 105 cells — low, clinically insignificant concentration: from 3 to 5 lg per 105 cells — average, clinically significant concentration: more than 5 lg per 105 cells — high. The effect of the drug on the dynamics of clinical manifestations of CIN was assessed by the results of a cytological study and/or extended colposcopy. Conclusion. The analysis of studies showed the high efficiency of alloferon against HPV in monotherapy (85%: elimination of HPV — 32%, a significant decrease in VL — 53%). Efficiency in complex therapy (93%: elimination of HPV — 89.7%, reduction in VN — 3.3%). The clinical efficacy of the drug in CIN 1 in monotherapy is 79.9%, and in the complex treatment of CIN 2 — 96.8%. Keywords: human papillomavirus, cervical intraepithelial neoplasia, recurrence, antiviral therapy, immunomodulatory therapy, alloferon.

Long-term effect of antiviral therapy for grade II cervical intraepithelial neoplasia

BACKGROUND: The production of many molecular markers at different grades of cervical intraepithelial neoplasia is currently being studied to predict the outcome of the disease and build an individual prognosis. However, no clear criteria for the course of neoplasia are available at this time.&#x0D; AIM: This study aimed to assess the efficiency of the antiviral immunomodulator Allokin-alpha (Alloferon) in the treatment of cervical intraepithelial neoplasia of moderate severity from the perspective of long-term follow-up.&#x0D; DESIGN: Prospective study.&#x0D; MATERIALS AND METHODS: We examined 86 women of reproductive age with grade II cervical intraepithelial neoplasia (CIN II) associated with human papillomavirus (HPV). In the CIN II group, all patients underwent excision of the affected area. According to the study design, 43 women were followed up after excision (Group 1a), while 43 participants were treated surgically and used the study drug (Group 1b). By cytological and colposcopic examination, the efficiency of the chosen therapy was assessed after 3, 12, and 18 months. However, the main criteria for the efficiency of treatment were the absence of HPV or a decrease in the viral load below significant values and the absence of recurrence of the pathological process.&#x0D; RESULTS: The combination of excision and the use of Allokin-alpha (Alloferon) showed significant advantages over monosurgical treatment.&#x0D; CONCLUSIONS: The data obtained indicate high HPV elimination and reduced probability of recurrence after excisional treatment in patients with CIN II when using Allokin-alpha (Alloferon).

Genetic deletion of HPV E7 oncogene effectively regresses HPV driven oral squamous carcinoma tumour growth

The major HPV oncogenes, E6 and E7, are known for its notoriety in driving the carcinogenic process in human papilloma virus (HPV) driven cancers. It is well-established that the removal of E7 dampens HPV cancer cell growth and proliferation. This has made E7 an attractive target for HPV cancers. Seminal work from our laboratory employed a CRISPR editing approach to delete E7 which resulted in the effective elimination of HPV+ cervical cancer tumours in vivo. We have also successfully delayed HPV+ tumour growth in vivo with aurora kinase (AURK) inhibitors, an effect which is strongly sensitized by the presence of E7. Unlike our previous observations in cervical cancer cells, in vitro targeting of E6/E7 have only resulted in partial killing of HPV+ oral squamous carcinoma (OSC) cells. However, the effect of sustained removal of E7 on HPV+ OSC tumour growth have not been explored. In this study, we investigated a staggered combination of aurora kinase inhibition, using alisertib, followed by CRISPR editing of E7, to determine if this would lead to better HPV+ OSC killing. Remarkably, genetic deletion of E7 alone was sufficient to effectively regress established HPV+ OSC tumours in vivo suggesting that E7 is essential in the maintenance of HPV+ OSC cancers.

Personalized tactics in cervical intraepithelial neoplasia of the cervix of varying severity

Purpose. To study the effectiveness of the drug diindolylmethane for the elimination of human papillomavirus (HPV) of high oncogenic risk in women with cervical intraepithelial neoplasia (CIN) of varying severity.&#x0D; Materials and methods. Conducted a comprehensive examination of 150 women, aged 20 to 49 years, with the presence of CIN. Verification of the diagnosis was carried out on the basis of data from clinical, cytological, colposcopic, and histological studies. HPV typing was carried out using the PCR (Kvant 21 test).&#x0D; Results. The obtained results emphasize the feasibility of using complex therapy for CIN of varying severity, including etiotropic correction of chronic cervicitis, with the parallel use of the drug diindolylmethane for 6 months, as well as destruction of the cervix in patients with CIN IIIII. The use of the drug diindolylmethane allows, with a statistical degree of certainty, to eliminate HPV of high oncogenic risk in patients with CIN of III.&#x0D; Conclusion. Despite the fact that we did not receive results indicating that it accelerates the elimination of HPV in patients with CIN III (p0.05), nevertheless, the use of diindolylmethane in patients with CIN III reduces the number of cases (p0.001) requiring expansion of surgical intervention (amputation of the cervix, extirpation of the uterus), which is important for patients of reproductive age.

Фотодинамическая терапия предрака и рака шейки матки с лазерным возбуждением флуоресценции с эффектом фотобличинга

Objective. To improve the efficacy of therapy for cervical intraepithelial neoplasia associated with human papillomavirus (HPV) infection using phototheranostics. Patients and methods. This study included 52 patients aged 22 to 53 years with morphologically confirmed diagnoses of cervical intraepithelial neoplasia of varying degrees, preinvasive, microinvasive and squamous cell cervical carcinomas. All women were carriers of HPV infection. Therapy control and HPV elimination were assessed by the results of polymerase chain reaction. Patients underwent photodynamic therapy (PDT) with simultaneous laser-induced fluorescence. Spectral fluorescence diagnostics of cervical neoplasms provided control of PDT at all stages of the procedure. The results of treatment were evaluated by extended colposcopy, cytological and histological examinations of biopsy material. Results. Treatment was found to be clinically effective, with 80.8% of patients showing regression of cervical lesions. Previously identified HPV types were not observed in 48 patients after the first PDT procedure, in 4 patients – after the second procedure. There was also a significant decrease in the expression of Ki67 and p16 markers in the cervical epithelium after PDT. Conclusion. The high clinical efficacy of phototheranostics, including PDT with the use of video and spectral fluorescence diagnostics, was shown both in terms of HPV elimination and treatment of cervical intraepithelial lesions. Key words: human papillomavirus, photodynamic therapy, cervical intraepithelial neoplasia, preinvasive cancer, cervical cancer, fluorescence diagnostics, photosensitizers

Эффективность локальной цитокинотерапии в комплексном лечении цервицита, ассоциированного с папилломавирусной инфекцией

Objective. To study the efficacy of local cytokine therapy with Superlymph® 25 units in the complex treatment of chronic cervicitis (vaginitis) combined with other lower urinary tract infections and associated with human papillomavirus (HPV) infection. Patients and methods. We conducted a comprehensive examination of 123 women aged 18 to 35, who were divided into two clinical groups. The control group included 50 patients with clinical and laboratory parameters corresponding to the standard reference ranges. The study group included 73 patients diagnosed with HPV-associated cervicitis and lower urinary tract infections. The laboratory examination included a vaginal pH test using colposcopy (colpotest), bacterioscopic and bacteriological methods, and a real-time polymerase chain reaction method. HPV typing was performed using a “Quantum 21” test. Results. Local cytokine therapy in the complex treatment of chronic cervicitis in patients with lower urinary tract infections contributes to the statistically significant restoration of vaginal microbiocenosis, promotes the growth of Lactobacillus biotype (p &lt; 0.001), reduces cervicitis and cystitis recurrence rates during the year (p &lt; 0.001), accelerates HPV elimination and reduces viral load (p &lt; 0.001). Conclusion. The use of local cytokine therapy with Superlymph® 25 units in the complex treatment of chronic cervicitis (vaginitis) in patients with lower urinary tract infections contributes to the restoration of vaginal microbiocenosis and reduction of cervicitis and cystitis recurrence rates during the year. Key words: human papillomavirus, cervicitis, lower urinary tract infections, cytokine therapy

The effect of vaginal probiotic therapy on the outcome of papillomavirus infection

Aim. To study the effect of vaginal probiotic therapy on the outcome of human papillomavirus (HPV) infection.Materials and methods. The study included HPV-infected patients: 29 patients with normal vaginal flora and 146 patients with a deficiency of vaginal lactobacilli, of which 117 patients received vaginal probiotic therapy. In samples obtained before and after the therapy, the effect of the probiotic on the change in the ratio of living, apoptotic, and necrotic vaginal epithelial cells after preliminary exposure to oxidative stress was studied.Results. It was found that probiotics reduce the number of infected epithelial cells that survived the oxidative damage and shift the balance of cell death forms towards apoptosis. Vaginal probiotic therapy in patients with a deficiency of lactobacilli increased the frequency of HPV elimination by 2.5 times and reduced the likelihood of treatment failure from 1.5 to 4 times, depending on the viral load. The probiotic therapy made the structure of HPV outcomes in Lactobacillus-deficient patients similar to that in patients with normal vaginal flora.Conclusion. Vaginal probiotic therapy improves outcomes of HPV infection in patients with a deficiency of lactobacilli by reducing the number of survived infected cells and shifting the cell death pattern towards apoptosis.

Muramyl peptides in the complex treatment of cervical intraepithelial neoplasia associated with human papillomavirus

Research objective: the use of an immunomodulator III generation with a wide range of action (muramyl peptide drug Liastenum) to increase the effectiveness of treatment of cervical intraepithelial neoplasia grade I associated with human papilloma virus (HPV) and to reduce the recurrence of cervical pathology.Materials and methods. The study included 60 women with histologically confirmed cervical intraepithelial neoplasia associated with highly oncogenic HPV. The mean age of patients was 25.92 ± 0.61 years. The first group included 30 women who received traditional treatment, the second group included 30 women who additional received Liastenum 0.002 g intramuscularly 1 time per day, 5 injections per course, after that patients took 1 tablets Liastenum twice a day for 20 days.Traditional treatment included antibiotic therapy (doxycycline monohydrate), metronidazole, nystatin in standard dosage. Patients with herpes viruses received valaciclovir 500 mg twice/day for 5 days. Evaluation of treatment efficacy was performed at 6 and 12 months with co-testing, fluid cytology, HPV quantification, and colposcopy.Results. There was a significant decrease in the exposure level of highly oncogenic HPV in the second group compared to the first: after 12 months in the first group HPV was not detected in 2 women (6.67%), and in the second group HPV was no detected in 17 women (56.67%) (p &lt; 0.05). Improvement of the colposcopic picture occurred in 70% of patients in the second group, and in 12 (40.0%) of patients colposcopic conclusion on the Swedish scale was less than 3 points after 12 months of observation. Only 8 (26.67%) women received improvement of the colposcopic picture with a score of 3 points on the Swedish scale in the first group, which was significantly different from the second group (p &lt; 0.05).Conclusions. Advanced therapy with muramyl peptide Liastenum in the treatment of cervix for 12 months can increase the effectiveness of HPV elimination, improves the colposcopic picture by reducing the area of cervical lesions and normalized cytological picture in 70% of patients with cervical intraepithelial neoplasia grade I.

Viral load as a factor of persistence of papillomavirus infection in cervical intraepithelial neoplasia grade I

Introduction. The viral antigenic load can influence the nature of the infectious response, leading to elimination of the virus or to chronicity of the process, and in some cases to the progressive course of the disease. The aim of the study was to investigate the relationship between the types of viral load of human papillomavirus and the age of a patient with cervical cervical intraepithelial neoplasia grade I. Material and methods. 86 patients with cervical papillomavirus-induced cervical intraepithelial neoplasia grade I by liquid oncocytology were examined. The frequency of human papillomavirus genotypes of high carcinogenic risk in this group of women was analyzed taking into account the viral load by polymerase chain reaction with real-time hybridization-fluorescence detection. The correlation between the viral load of the human papillomavirus and the age of the patient with further prediction of the regression or progression of cervical pathology was studied. Results. This study found that female patients under 30 years of age with cervical intraepithelial neoplasia grade I associated with papillomavirus infection showed a decrease in viral load after 12 months of follow-up in 30.2%, and in patients with cervical intraepithelial neoplasia grade I of older age — in 9.3%. Discussion. The management tactics for grade I cervical intraepithelial neoplasia associated with papillomavirus infection depends largely on the age of the patients and the degree of viral load. In young patients with immediate reproductive plans, a wait-and-see approach with dynamic observation for 12 months without drug therapy is possible in view of the probable spontaneous elimination of the human papillomavirus within a year. The results of the study suggest a higher rate of human papillomavirus elimination in cervical intraepithelial neoplasia grade I in women under 30 years of age. Conclusion. In cervical intraepithelial neoplasia of degree I in women under 40, infection with several types of the human papilloma virus (16, 18, 31, 51) with a clinically significant viral load (over 4.69±0.07 HPV per 100,000 cells) was found most frequently. In the group of the older reproductive age (40-49 years old), HPV HCC is less frequent in 6.90%. And the predominant role belongs to type 16, which was spread in 69.7% of cases.

Efficacy of immunological antivirus therapy for papillomavirus-associated grade I cervical intraepithelial neoplasia

AIM: The study aimed to assess the effectiveness of alloferon in human papillomavirus (HPV)-associated cervical neoplasia (grade I) based on the analysis of the cytokine profile in cervical mucus as well as markers of apoptosis in cervical epithelial cells.&#x0D; MATERIALS AND METHODS: The study enrolled 98 women, including 55 women of reproductive age with cervical intraepithelial neoplasia (CIN) associated with HPV infection and 43 conditionally healthy women without HPV infection. Factors of cytokine response and markers of apoptosis under normal and pathology conditions were assessed and compared.&#x0D; RESULTS: The imbalance of pro-inflammatory and anti-inflammatory cytokines, in favor of the latter, is an important factor that supports the persistence of HPV-associated grade I CIN. Reducing caspase-3 and caspase-9, increasing interleukin-18, and subsequent activation of interferon gamma against the background of alloferon use are favorable signs of substantial elimination of the HPV.&#x0D; CONCLUSIONS: The results of this study show considerable elimination of HPV in patients with grade I CIN when using immunological antivirus therapy.

EXPERIENCE OF IMMUNOCORRECTIVE TREATMENT IN THE MANAGEMENT OF PATIENTS WITH CERVICAL INTRAEPITHELIAL NEOPLASIA ON THE BACKGROUND OF GENITAL PAPILLOMAVIRUS INFECTION

Introduction. Human papillomavirus (HPV), its highly oncogenic types, is considered to be the initiating factor in the development of dysplasia and cervical cancer The role of immunomodulatory therapy in reducing the risk of cervical cancer in women with cervical intraepithelial neoplasia (CIN) associated with HPV infection remains in the focus of researchers. Aim of the study: to evaluate the effectiveness of the use of the immunomodulator Allokin-alfa in the complex treatment of cervical intraepithelial neoplasia against the background of genital papillomavirus infection. Materials and methods. We examined 60 women who received CIN1- 2 treatment on the background of HPV infection of high oncogenic risk in the multidisciplinary medical center of the Odessa National Medical University. The patients were divided into 2 groups: 1 (main) group consisted of 30 women who received cold plasma ablation of cervical dysplasia in combination with immunomodulatory therapy with alloferon, group 2 (comparison) consisted of 30 patients who received standard cold plasma ablative treatment without immunomodulators. The control group consisted of 30 healthy women. All women underwent cytomorphological examination of the cervical epithelium, HPV testing, colposcopy, and targeted biopsy. Immunological status was assessed by indicators of cellular and humoral immunity, the content of α- and γ-interferon. Results. In patients with CIN1-2 against the background of HPV, an increase in the level of serum Ig A, CD8 level, a decrease in the CD4 content and immunoregulatory index, CD19 content were revealed, which indicated immunosuppression. Immunocorrective therapy witn alloferon (Allokin-alfa) in complex, with cold plasma ablation, treatment of CIN1-2 promoted the normalization of the parameters of immunity and interferon status, which contributed to the acceleration of epithelialization, (OR — 15,48; 95% CІ: 2,05-136,45; р=0,0094). a decrease in the frequency of residual lesions, and a HPV elimination. Conclusions. Complex treatment of CIN1-2 using cold plasma ablation and immunocorrection by perioperative administration of alloferon (Allokin-alfa) is accompanied by better functional results, compared only with the use of cold plasma ablation: accelerated epithelialization, improved colposcopic picture, decreased frequency of relapses, elimination of HPV, normalization of immunе and interferon status.

Интравагинальная пробиотическая терапия как способ управления ВПЧ-инфекцией женских гениталий

Objective. To study the possibility of managing human papillomavirus (HPV) infection using intravaginal probiotic therapy. Patients and methods. In the first phase, a retrospective analysis of outpatient medical records of 125 patients for 2 years was caried out to assess the HPV infection outcomes depending on the initial viral load and the state of normal microbial flora. In the second phase (prospective analysis), 43 HPV-positive patients with Lactobacillus deficiency who received (n = 20) or did not receive (n = 23) intravaginal probiotic were selected. The dynamics of HPV viral load were evaluated during the study. The dynamics of Lactobacillus abundance under the influence of probiotic in the groups with different HPV infection outcomes were analyzed. Results. The outcome of HPV infection with HPV viral load of ≤5 lg DNA copies/106 cells depended on the state of normal microbial flora; the value of normal microbial flora with HPV viral load of 5 lg DNA copies/106 cells was not significant. Intravaginal probiotic therapy in combination with antiviral drug in HPV-positive patients with Lactobacillus deficiency was more effective in improving the HPV infection outcomes. A decrease in viral load or HPV elimination was more likely to occur if normal microbial flora was restored as a result of probiotic therapy. Conclusion. Adding intravaginal probiotic therapy with Lactoginal® to antiviral treatment is an effective way to manage HPV infection in the female reproductive tract. Key words: human papillomavirus, vagina, lactobacilli, cervix, epithelial cells

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

IMMUNONUTRITION IN CERVICAL CANCER: IMMUNE RESPONSE MODULATION BY DIET.

In the development of cervical cancer (CC), the immune response plays an essential role, from the elimination of human papillomavirus (HPV) infection to the response against the tumor. For optimal function of the immune response, various factors are required, one of the most important being an adequate nutrition. The complex interaction between nutrients and microbiota maintains the immune system in homeostasis and in case of infection, it provides the ability to fight against pathogen invasion, as occurs in HPV infection. The purpose of this article is to describe the role of diet, food, and specific nutrients in the immune response from the onset of infection to progression to precancerous lesions and CC, as well as the role of diet and nutrition during oncological treatment. The immunomodulatory role of microbiota is also discussed. A detailed analysis of the evidence leads us to recommend a nutritional pattern very similar to the Mediterranean diet or the prudent diet for an optimal immune response. Moreover, pre- and probiotics favorably modulate the microbiota and induce preventive and therapeutic effects against cancer.