HPV E6/E7mRNA association with interleukin 10 (rs1800872) polymorphism in a group of Macedonian women.

Interleukin 10 (IL-10) is an immunosuppressive cytokine and its genetic variants could have an indirect impact on viral biology and human papillomavirus (HPV) E6/E7 messenger RNA (mRNA) expression as well. This study evaluates the association between IL-10-592 C/A (rs1800872) single-nucleotide polymorphism and HPV E6/E7 mRNA expression in a group of women from the Republic of North Macedonia. Using a commercial test, 272 women's cervical samples were analyzed for HPV E6/E7 mRNA and HPV DNA presence. The cases were stratified into three groups: double-positive (n = 108, positive for both tests), negative (n = 51, negative for HPV E6/E7 mRNA and HPV DNA positive), and the control group (n = 113, negative for both tests). The IL-10-592 C/A polymorphism was analyzed using polymerase chain reaction-restriction fragment length polymorphism. The results showed the CC genotype and the C allele frequencies of IL-10-592C/A were significantly higher in double-positive (59.3% and 78.2%) compared to negative group (39.2% and 65.7%), (p = 0.018, confidence interval [CI] = 2.25; 1.14-4.45 and p = 0.016, CI = 1.88; 1.11-3.16, respectively). The CC genotype and C allele of rs1800872 polymorphism were shown to be associated with HPV E6/E7 mRNA but not with HPV DNA positivity, which implies a possible role of this polymorphism in the course of the infection only after HPV onset, and lack of association with the susceptibility to HPV.

Management of patients with positive margin after conization for high-grade cervical intraepithelial lesions.

BACKGROUND AND OBJECTIVE: To evaluate the clinical efficacy and safety of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in the treatment of patients with positive margin in comparison to regular follow-up, and a repeat cervical conization. MATERIALS AND METHODS: A retrospective analysis was conducted using 83 patients with pathologically confirmed high-grade cervical intraepithelial neoplasia (CIN) with a positive margin after conization. The management methods and patient prognosis were analyzed and compared. RESULTS: Thirty-five, 33, and 15 patients were treated for regular follow-up, ALA-PDT, and a repeat cervical conization, respectively. About 33.3% (5/15) patients had residual lesions of low-grade CIN and above after recognization. The clinical characteristics of patients in the three groups were similar. The residual lesion rates of patients selected for follow-up, ALA-PDT, and recognization were 34.3% (12/35), 9.1% (3/33), and 0% (0/15), respectively, at 6-month follow-up (p = 0.004). The HPV clearance rates were 31.3%, 66.7%, and 84.6%, respectively (p = 0.01). Further analysis showed that a positive margin in the inscribed margin of the cervical canal (p = 0.022) and persistent HR-HPV positive tests after initial conization (p = 0.003) significantly increased the risk of residual disease. At 2-year follow-up, the recurrence rates of lesions were 3.3% and 26.1% in the ALA-PDT and follow-up groups, respectively (p = 0.021). Notably, the recurrence rates were not significantly different between the ALA-PDT and recognization groups (3.3% vs. 6.7%) (p = 0.561). CONCLUSION: ALA-PDT is an effective treatment for patients with a positive margin after cervical conization for high-grade CIN. Compared with regular follow-up, ALA-PDT can reduce residual and recurrence rate. Moreover, there was no significant difference in the efficacy between AlA-PDT and recognization.

Risks for cervical abnormalities in women with non-16/18 high-risk human papillomavirus infections in south Shanghai, China.

The study was aimed to analyze the prevalence characteristics of non-16/18 high-risk human papillomaviruses (HR-HPV) and the related risks for cervical abnormalities in south Shanghai. A total of 2291 HPV women who had been referred for a colposcopy due to HPV infection from @@@@@2016.12 to 2019.6 were enrolled. Combined with liquid-based thin-layer cell test (TCT) and pathological results of cervical biopsy, the infection spectrum and pathogenic risk of non-16/18 HR-HPV in local population were investigated. The results showed that the single HR-HPV infection rate was significantly higher than that of multiple infection, and the five most frequently detected types were HPV16, HPV52, HPV18, HPV53, HPV58 in the group. The total proportion of non-16/18 HR-HPV infection was 68.22%, more than twice of HPV16/18. In cases with high-grade cervical intraepithelial lesions (HSIL) or cervical cancer, non-16/18 HR-HPV infections account for 50.84% (single infection: 28.57%, multiple infection: 22.27%). The risk of cervical abnormalities caused by single HPV infection was ranked as HPV16 > HPV52 > HPV18 = HPV58 > HPV51 > HPV53 = HPV56 > others. Notably, among non-16/18 HR-HPV infected patients with HSIL/cancer lesions, the omission diagnostic rate of TCT was 62.81%. The infection rate of non-16/18 HR-HPV in whole study population was much higher than that of 16/18 type, and the infection rate of the former was also slightly higher in patients with HSIL and cancer. Due to the high omission diagnostic rate of TCT, we suggest patients with persistent non-16/18 HPV infection should undergo colposcopy biopsy to reduce missed detection of HSIL and cancers.

Incidence of cervical intraepithelial lesions and human papilloma virus infection in female renal transplant recipients.

BACKGROUND: Female renal transplant recipients (RTR) are at high risk of human papillomavirus (HPV)-related anogenital premalignancies and cancer. The aim of this study was to estimate the incidence of cervical intraepithelial lesions (IL) and HPV infection, and their associated factors, in Mexican RTR. METHODS: This is a prospective cohort study conducted between January 2011 and December 2017. Demographic, clinical, and gynecological data were collected using a previously designed questionnaire. Gynecological examination, cervical cytology, and detection of high- and low-risk HPV DNA were undertaken prior to and after the renal transplant (RT). Colposcopically guided biopsies were obtained from patients who presented high grade squamous intraepithelial lesions (HSIL) during the follow-up period. Diagnoses were established according to the Bethesda system. RESULTS: Among 130 RTR, 62 were eligible for our study. The overall incidence of IL was 17.7% (95% CI, 8% to 27%), (11/62 patients), at 25.6 ± 10.7 months post-RT. Nine out of the eleven affected patients had low-grade squamous intraepithelial lesions (81.8%) and only two had HSIL (18.2%). The incidence of HPV infection, determined in a subgroup of 30 RTR, was 53.3% (95% CI, 35% to 71%), (16 out of 30 patients), at 18.3 ± 8.9 months post-RT. High-risk HPV genotypes were present in 62.5% of HPV positive cases (10/16). In 11 patients (36.6%), HPV infection was not associated to IL. CONCLUSIONS: HPV infection and cervical IL are common in the early posttransplant period. Our findings support the need of screening for cervical cancer to detect precancerous changes in RTR and the need of strengthening the knowledge of medical personnel on this issue.

Cervical adenocarcinoma in situ: Human papillomavirus types and incidence trends in five states, 2008-2015.

Primary prevention through the use of human papillomavirus (HPV) vaccination is expected to impact both cervical intraepithelial neoplasia (CIN) and adenocarcinoma in situ (AIS). While CIN is well described, less is known about the epidemiology of AIS, a rare cervical precancer. We identified AIS and CIN grade 3 (CIN3) cases through population-based surveillance, and analyzed data on HPV types and incidence trends overall, and among women screened for cervical cancer. From 2008 to 2015, 470 AIS and 6,587 CIN3 cases were identified. The median age of women with AIS was older than those with CIN3 (35 vs. 31 years; p < 0.01). HPV16 was the most frequently detected type in both AIS and CIN3 (57% in AIS; 58% in CIN3), whereas HPV18 was the second most common type in AIS and less common in CIN3 (38% vs. 5%; p < 0.01). AIS lesions were more likely than CIN3 lesions to be positive for high-risk types targeted by the bivalent and quadrivalent vaccines (HPV16/18, 92% vs. 63%; p < 0.01), and 9-valent vaccine (HPV16/18/31/33/45/52/58, 95% vs. 87%; p < 0.01). AIS incidence rates decreased significantly in the 21-24 year age group (annual percent change [APC] overall: -22.1%, 95% CI: -33.9 to -8.2; APC among screened: -16.1%, 95% CI: -28.8 to -1.2), but did not decrease significantly in any older age group. This report on the largest number of genotyped AIS cases to date suggests an important opportunity for vaccine prevention of AIS, and is the first to document a decline in AIS incidence rates among young women during the vaccine era.

Positive staining of the immunoligand B7-H6 in abnormal/transformed keratinocytes consistently accompanies the progression of cervical cancer.

BACKGROUND: B7-H6 has been revealed as an endogenous immunoligand expressed in a variety of tumors, but not expressed in healthy tissues. Heretofore, no studies have been reported describing B7-H6 in women with cervical cancer. To investigate this question, our present study was conducted. RESULTS: This retrospective study comprised a total of 62 paraffinized cervical biopsies, which were distributed in five groups: low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), squamous cervical carcinoma (SCC), uterine cervical adenocarcinoma (UCAC), and a group of cervicitis (as a control for non-abnormal/non-transformed cells). Cervical sections were stained by immunohistochemistry to explore the expression of B7-H6, which was reported according to the immunoreactive score (IRS) system. We observed a complete lack of B7-H6 in LSIL abnormal epithelial cells. Interestingly, B7-H6 began to be seen in HSIL abnormal epithelial cells; more than half of this group had B7-H6 positive cells, with staining characterized by a cytoplasmic and membranous pattern. B7-H6 in the SCC group was also seen in the majority of the sections, showing the same cytoplasmic and membranous pattern. Strong evidence of B7-H6 was notably found in UCAC tumor columnar cells (in 100% of the specimens, also with cytoplasmic and membranous pattern). Moreover, consistent B7-H6 staining was observed in infiltrating plasma cells in all groups. CONCLUSIONS: B7-H6 IRS positively correlated with disease stage in the development of cervical cancer; additionally, B7-H6 scores were found to be even higher in the more aggressive uterine cervical adenocarcinoma, suggesting a possible future therapeutic target for this cancer type.

Association of TNF-a (rs361525 and rs1800629) with susceptibility to cervical intraepithelial lesion and cervical carcinoma in women from Republic of North Macedonia.

Cervical cancer (CCa) is one of the most common malign diseases in women associated with human papillomavirus (HPV). The virus is an initiating factor, but not sufficient for the development of cervical intraepithelial lesions (CIN) and CCa. The disease might be a result of the influence of host's genetic factors and polymorphisms in inflammatory-related genes that modify the immune response to HPV and attribute to cancer susceptibility. We carried out a study to determine the association between TNF-a-238G/A and TNF-a-308 G/T polymorphisms with HPV-positive CIN and CCa in women living in the Republic of North Macedonia. Using multiplex SNaPshot analysis for single nucleotide polymorphisms (SNPs), we analysed the genotype and allele distributions of TNF-a-238G/A and TNF-a-308 G/T in 134 cases (HPV-positive and histologically confirmed CIN and CCa) and in 113 controls (cytological and HPV-negative women). For further analysis, the case group was stratified in three subgroups (all cases: CINs+ CCa- group; CIN2+ -group and CIN1- group). Data analysed using the odds ratio (OR) and chi-square test showed the frequency of AA genotypes and A alleles are not significantly higher in cases compared to the controls for both SNPs: AA of TNF-a-238 (0.7% versus 0%) and TNF-a-308 (1.5% versus 0.9%) as well as A allelic frequency (3.0% versus 1.7%) and (13.1% versus 10.6), respectively. The comparison of the case's subgroups with the control group did not show a statistically significant difference. Compared to controls, TNF-a-238G/A and TNF-a-308 G/T are not associated with the risk of HPV associated CIN or CCa in the studied women.

CCR5 genetic variants and epidemiological determinants for HPV infection and cervical premalignant lesions.

Human papillomavirus (HPV) infection can lead to the development of productive epithelial lesions and cervical cancer. Most cervical HPV infections are solved by cell-mediated immunity within 1-2 years, and it is known that chronic inflammation predisposes to lesions progression and tumour development. In this context, we highlight the CC chemokine receptor 5 (CCR5) which is involved in leucocytes chemotaxis to sites of inflammation, controlling the immune response. The CCR5 rs333 genotyping of 164 HPV infected women and 185 non-infected women was performed using polymerase chain reaction (PCR). HPV infection was more frequent among women under 34 years old (p < 0.001), single (p = 0.001), that received 1 minimum wage or less (p = 0.002), tobacco smokers (p = 0.007), who had the first sexual intercourse before 17 years old (p = 0.038) and that had 4 or more sexual partners during lifetime (p = 0.001). No significant difference regarding genotypes and alleles distribution according to HPV infection was observed. CCR5/CCR5 genotype was observed in 94.1% of HPV non-infected women and in 89% of infected ones, CCR5/Δ32 in 5.9% of HPV infected and in 10.4% of non-infected women, and Δ32/Δ32 was observed in only one (0.6%) infected patient. CCR5 genotypes were also not associated with cervical lesions development among HPV infected women (p = 0.167). Since CCR5 may control the antitumour immune response and cervical lesions and the studied rs333 polymorphism is not very frequent, other studies are necessary, in order to establish CCR5 role on HPV infection and squamous intraepithelial lesions development.

Conservative management of biopsy confirmed high-grade squamous intraepithelial lesions.

OBJECTIVES: Follow-up of women with biopsy-confirmed CIN2+ who were either treated immediately with LLETZ or managed conservatively to determine the rates of patients back on routine screening programme after a median of three years in two groups. METHODS: In this retrospective study, 310 patients were involved who had undergone biopsy with result of CIN2+ between January 2011 and December 2014. Depending on the management, i.e. based on whether cytology and colposcopy follow-up or immediate treatment were performed, they were divided in two groups. Then the number of patients back on routine screening up to 15/2/2016 as well as the results of last cytology were compared within both groups. RESULTS: A total of 310 women at average age of 30 years met the inclusion criteria. Of them, 230 (74 %) had immediate treatment whereas 80 (26 %) were managed conservatively. There were no statistically significant demographic differences between the two groups. The mean time of follow up was 1.091 days (2.98 years). The patients managed conservatively required more follow-up visits at colposcopy clinic (p<0.001). The last documented cytology in the immediate treatment group was negative in 93 % and low-grade/borderline in 7 % of patients, while in the conservative management group, it was negative in 84 %, low-grade/borderline in 15 % and high-grade in 1 % of patients (p = 0.015). Overall, the proportions of patients who are back on routine screening recall are 96 % and 87.5 % for the immediate treatment and conservatively managed groups, respectively (p=0.022). CONCLUSION: The conservative management of high-grade CIN with cytology and colposcopic follow up is an OPTION in selected group of patients, but it cannot be routinely recommended (Tab. 2, Ref. 20).

Could 25-OH vitamin D deficiency be a reason for HPV infection persistence in cervical premalignant lesions?

Vitamin D is an essential precursor to the steroid hormone calcitriol which mainly regulates calcium homeostasis. Moreover anti- proliferative, pro- apoptotic, anti- angiogenic effects of Vitamin D support the ideas of preventive role in various cancer. This study aimed to determine if there is a relationship between HPVDNA infection and cervical intraepithelial neoplasia and Vitamin D deficiency. As a result of the study the difference of 25-OH Vitamin D3 levels between HPVDNA positive group and the control group were statistically significant (p=0,009). According to results of our study, with the proven anti-inflammatory functions of Vitamin D, the deficiency of these molecule and its metabolites can be a possible reason for HPVDNA persistence and related cervical intraepithelial neoplasia.

Recurrence of cervical intraepithelial lesions after thermo-coagulation in HIV-positive and HIV-negative Nigerian women.

BACKGROUND: The burden of cervical cancer remains huge globally, more so in sub-Saharan Africa. Effectiveness of screening, rates of recurrence following treatment and factors driving these in Africans have not been sufficiently studied. The purpose of this study therefore was to investigate factors associated with recurrence of cervical intraepithelial lesions following thermo-coagulation in HIV-positive and HIV-negative Nigerian women using Visual Inspection with Acetic Acid (VIA) or Lugol's Iodine (VILI) for diagnosis. METHODS: A retrospective cohort study was conducted, recruiting participants from the cervical cancer "see and treat" program of IHVN. Data from 6 sites collected over a 4-year period was used. Inclusion criteria were: age ≥18 years, baseline HIV status known, VIA or VILI positive and thermo-coagulation done. Logistic regression was performed to examine the proportion of women with recurrence and to examine factors associated with recurrence. RESULTS: Out of 177 women included in study, 67.8 % (120/177) were HIV-positive and 32.2 % (57/177) were HIV-negative. Recurrence occurred in 16.4 % (29/177) of participants; this was 18.3 % (22/120) in HIV-positive women compared to 12.3 % (7/57) in HIV-negative women but this difference was not statistically significant (p-value 0.31). Women aged ≥30 years were much less likely to develop recurrence, adjusted OR = 0.34 (95 % CI = 0.13, 0.92). Among HIV-positive women, CD4 count <200cells/mm(3) was associated with recurrence, adjusted OR = 5.47 (95 % CI = 1.24, 24.18). CONCLUSION: Recurrence of VIA or VILI positive lesions after thermo-coagulation occurs in a significant proportion of women. HIV-positive women with low CD4 counts are at increased risk of recurrent lesions and may be related to immunosuppression.

Inhibitory effect and mechanism of Lactobacillus crispatus on cervical precancerous cells Ect1/E6E7 and screening of early warning factors.

OBJECTIVE: To study the potential mechanism of Lactobacillus crispatus inhibiting cervical squamous intraepithelial lesion (SIL) and screen the early warning factors of SIL. METHODS: The effects of Lactobacillus crispatus on the proliferation, apoptosis, cross pore migration and invasion and cytokines of cervical precancerous cells Ect1/E6E7 were detected respectively. The effect of Lactobacillus crispatus on the expression of differential proteins screened in Ect1/E6E7 cells were detected by Western blot. RESULTS: Lactobacillus crispatus significantly inhibited the proliferation, induced apoptosis and inhibited cell migration of Ect1/E6E7 cells in a time-dependent manner (P < 0.05), but had no significant effect on cell invasion. Lactobacillus crispatus significantly promoted the secretion of Th1 cytokines and inhibited the secretion of Th2 cytokines by Ect1/E6E7 cells (P < 0.05). In addition, compared with SiHa cells in the control group, the expression of differential proteins PCNA, ATM, LIG1 and HMGB1 in Ect1/E6E7cells decreased significantly, while the expression of TDG and OGG1 proteins increased significantly (P < 0.05). ABCG2 protein in Ect1/E6E7 cells was slightly higher than that in SiHa cells, but the difference was not statistically significant. What is interesting is that Lactobacillus crispatus significantly inhibited the expression of ABCG2, PCNA, ATM, LIG1, OGG1 and HMGB1 proteins in Ect1/E6E7 cells, and promoted the expression of TDG protein. CONCLUSIONS: Lactobacillus crispatus may inhibit the function of Ect1/E6E7 cells through multiple pathways and exert the potential to reverse the progression of SIL.

Risk of human papillomavirus infection and cervical intraepithelial lesions in Chinese renal transplant recipients.

Objective: While human papillomavirus (HPV) infection in women is associated with cervical intraepithelial neoplasia and cervical cancer, HPV testing is not often performed in routine practice for renal transplantation patients. The genotype-specific prevalence of HPV and risk factors for HPV infection are still unclear. Methods: From 2010 to 2020, patients receiving renal transplantation surgery (referred to as RTRs), who had been screened for HPV infection one year after transplantation were enrolled. A comparison cohort of four age- and marital status-matched healthy individuals was selected for RTRs. The clinical characteristics and cervical screening results of RTRs were analyzed. Results: Our study included 196 female renal transplant recipients (RTRs), none of whom had been vaccinated against HPV. Overall high-risk HPV (hrHPV) infection and abnormal cytology rates in the RTR group were 23.5% and 20.9%, respectively. The odds ratios of hrHPV infection and cervical intraepithelial neoplasia grade 2+ in RTRs vs. non-RTRs were 3.033 (95% CI, 2.013-4.568) and 3.628 (95% CI, 1.863-7.067), respectively. The prevalence of HPV16 in RTRs was much higher (30.4% vs. 8.3%, P=0.002). The multi-infection rate was much higher in HPV-infected RTRs (23.9% vs. 1.14%, P<0.001). The only risk factor for hrHPV infection was the duration of immunosuppression, which increased with time. Conclusion: RTRs had significantly higher HPV infection rates and increased risks of HPV-related cervical premalignancies and cancers due to the immunosuppressed state. The duration of immunosuppression is a risk factor for transplant recipients. Female RTRs may benefit from more frequent cervical cancer screening after renal transplantation than healthy women. Prospective research on HPV infection dynamics in RTRs and optimal screening methods should be further explored in the future.

Development of cervical intraepithelial lesions and cervical cancer is not influenced by SOD2 RS4880 polymorhism.

Some of the more than 200 known HPV types are essential for cervical cancer development, the third type of cancer most incident in the female population. However, for the malignant transformation occur, some cofactors are needed, as the reactive oxygen species (ROS), which can be neutralized by the antioxidant system. The SOD2 enzyme, encoded by the same name gene, is found in mitochondria and is part of the first line of defense against oxidative stress damage. Genetic polymorphisms can act by altering the efficiency of the enzyme, among which the most studied is the rs4880. Thus, the purpose of the present study was to evaluate the association of this polymorphism with HPV infection and the development of low and high grade squamous intraepithelial lesions (LSIL and HSIL) and cervical cancer, in 407 women attended by the public health system in Brazil. HPV detection in cervical secretion samples was carried out by polymerase chain reaction (PCR) and blood samples were used for polymorphism genotyping through PCR followed by restriction fragment length polymorphism (RFLP). PCR and restriction products were subjected to 10% polyacrylamide gel electrophoresis. HPV negative group (control) included 158 women and the HPV positive group (case) 249 women. The infected group was divided into No Lesion (n = 90), LSIL (n = 20), HSIL (n = 67) and cervical cancer (n = 72). The data found on socio-epidemiological characteristics and habits corroborated with data found in the literature. The distribution of genotypes in the control group was 51.9% women TC, 29.8% TT and 18.3% CC. In the case group, the distribution was 55.0% women TC, 26.1% TT and 18.9% CC. This is the first study evaluating the influence of SOD2 rs4880 polymorphism on HPV infection, the development of cervical intraepithelial lesions and cervical cancer in a Brazilian population, although additional studies are needed to corroborate the results.

Distribution of Human Papillomavirus (HPV) Genotypes in HIV-Negative and HIV-Positive Women with Cervical Intraepithelial Lesions in the Eastern Cape Province, South Africa.

South African women have a high rate of cervical cancer cases, but there are limited data on human papillomavirus (HPV) genotypes in cervical intraepithelial neoplasia (CIN) in the Eastern Cape province, South Africa. A total of 193 cervical specimens with confirmed CIN from women aged 18 years or older, recruited from a referral hospital, were tested for HPV infection. The cervical specimens, smeared onto FTA cards, were screened for 36 HPV types using an HPV direct flow kit. HPV prevalence was 93.5% (43/46) in CIN2 and 96.6% (142/147) in CIN3. HIV-positive women had a significantly higher HPV prevalence than HIV-negative women (98.0% vs. 89.1%, p = 0.012). The prevalence of multiple types was significantly higher in HIV-positive than HIV-negative women (p = 0.034). The frequently detected genotypes were HPV35 (23.9%), HPV58 (23.9%), HPV45 (19.6%), and HPV16 (17.3%) in CIN2 cases, while in CIN3, HPV35 (22.5%), HPV16 (21.8%), HPV33 (15.6%), and HPV58 (14.3%) were the most common identified HPV types, independent of HIV status. The prevalence of HPV types targeted by the nonavalent HPV vaccine was 60.9% and 68.7% among women with CIN2 and CIN3, respectively, indicating that vaccination would have an impact both in HIV-negative and HIV-positive South African women, although it will not provide full protection in preventing HPV infection and cervical cancer lesions.

Identification of autophagy-associated miRNA signature for the cervical squamous cell cancer and high-grade cervical intraepithelial lesions.

Cervical cancer markedly threatens women's health worldwide and currently ranks fourth leading cause of cancer mortality in women according to recent global cancer statistics. Recent advances have proven that not only tumor suppressor and oncogenes but also non-coding RNAs including micro RNAs (miRNAs) have significant impact in the development and progression of cervical cancers. Previous studies have identified many cancer-specific miRNAs for the early detection of cervical cancers. However, the diagnostic and prognostic use of autophagy-associated miRNAs for the cervical squamous cell cancer (SCC) cases and high-grade squamous intraepithelial lesion (HSIL) have not been uncovered. In the present study, we revealed that miRNAs are differentially expressed in both cervical SCC and HSIL. A total of 35 HSIL, 35 cervical SCC and 30 healthy controls were enrolled for the present study. Total RNA including miRNAs were isolated from the FFPE tissue samples and miRNA expression levels were quantified by quantitative PCR. Predicted miRNA targets of autophagy related genes were determined using miRNA-target prediction algorithms. MiR-143, miR-372, miR-375 and miR-30c were markedly downregulated in HSIL and cervical SCC. MiR-130a was significantly upregulated in the cervical SCC group compared to HSIL and control groups. MiR-30a, miR-520e, miR-548c and miR-372 were significantly associated with the overall survival of cervical SCC patients and these miRNAs were determined to be significant diagnostic markers as revealed by ROC analysis. Together, these results indicate that autophagy-associated miRNAs are potentially valuable for the differential diagnosis and targeted therapy to cervical cancer.

The impact of concurrent HPV infections on the presentation of high grade cervical intraepithelial lesions.

OBJECTIVES: We investigate how concurrent high-risk (hr) HPV (human papillomavirus) genotypes affect CIN2-3 risk and evaluate the relationship of different genotype combinations with cervical epithelial lesions. MATERIAL AND METHODS: This study included HPV positive patients between the ages of 30 and 60 who underwent liquid-based cervical smears and HPV screening through community-based, cervical cancer screening programs between June 2015 and June 2017. The impact of the increase in hrHPV types was calculated by estimating how it changed the odds ratio of CIN2-3 risk. RESULTS: The rate of multiple concurrent HPV infections was 48.7% in the CIN2-3 group and 58.4% in the CIN1 group. Among patients in the CIN2-3 and CIN1 groups, the most common HPV coinfection was respectively HPV 16+31 and HPV 16+51. The HPV 51 ratio in CIN1 patients was 28.9% and the HPV 51 ratio in the CIN2-3 patient was 6.6%. With every increase in the number of hrHPV infection types, the frequency of CIN2-3 decreased [OR: 0.72, 95% CI: 0.54-0.95]. For all hrHPV combinations, the addition of HPV 16 was associated with a higher risk of CIN2-3. CONCLUSIONS: An increase in number of hrHPV types is associated with lower CIN2-3 risk. Further cohort studies with larger samples are needed to clarify this relationship. The available evidence suggests that HPV 16 genotype plays an important role in patients with high-grade cervical lesions and has a negative impact on the cervix in concurrent multiple HPV infections.

Reliability of colposcopy during pregnancy.

OBJECTIVE: To investigate the reliability of colposcopy during pregnancy and to evaluate the concordance between colposcopic patterns and histopathological findings in these women. STUDY DESIGN: Multicenter observational study of women diagnosed with an abnormal cervical cytology, who subsequently underwent a colposcopic evaluation with cervical biopsy during pregnancy. The "colpo-histopathological concordance‿ was evaluated. The "colposcopic overestimation and underestimation‿ were evaluated as well. RESULTS: 69 women, fulfilling the study inclusion/exclusion criteria, constituted the study cohort. Among them, on colposcopic examination, 14 women (20.3%) showed "grade I abnormal colposcopic findings‿, 52 (75.4%) showed "grade II abnormal colposcopic findings‿ and the remaining 3 women (4.3%) had a "suspicious for invasion‿ colposcopy. The histopathological diagnosis showed 2 negative biopsies, 12 (17.4%) cases of CIN1, 50 (72.5%) cases of CIN2 and 5 (7.2%) cases of invasive cervical cancer. We found a colposcopic overestimation in 10 cases (14.5%), underestimation in 12 cases (17.4%), and a concordance in 47 cases (68.1%). A better reliability of colposcopy in women in the firsts two trimesters and in particular in women ≤20 weeks pregnant was found (Cohen's weighted kappa: 0.65). CONCLUSIONS: When performed by gynecologists with expertise, colposcopy is a reliable diagnostic tool, even during pregnancy. Whenever possible, a colposcopic evaluation during the first half of pregnancy is preferable.

Prevalence of HPV infection and cervical intraepithelial lesions in HIV positive and negative women in the city of Florianopolis / Prevalência da infecção pelo HPV e lesões intraepiteliais cervicais em mulheres HIV positivas e negativas na cidade de Florianópolis

Introduction: HPV infection is the most frequent sexually transmitted infection in women. The high oncogenic risk HPV, associated with others factors, there are a risk of progressing to a precancerous lesion of the cervix and even cancer. This evolution is related to the persistence of the infection and other factors, mainly those that interfere with the woman's immunity. The immunosuppression caused by HIV infection is an important factor for viral persistence and the appearance of these lesions. Objectives: To compare the prevalence of HPV infection and cervical intraepithelial lesions in HIV-positive and negative women and describe the possible associated risk factors. Methods: The sample consisted of 50 HIV positive women (study group) and 50 HIV negative women (control group) recruited from the public health system of Florianópolis during the months of January to April 2022. Cervical samples were collected for cytological analysis and for detection of high-risk oncogenic HPV DNA by polymerase chain reaction (PCR). Categorical variables were compared using the chi-square test, with a significance level set at 5% Results: HPV infection was more prevalent in the control group, however, HIV positive women had a higher frequency of intraepithelial lesions diagnosed on cytology. Factors such as greater number of sexual partners, depression and smoking were more frequent in the group of HIV positive women. The number of CD4 T cells less than 200 cels/mm3 was associated with a higher number of altered Pap smears and a positive HPV DNA test. The use of combination antiretroviral therapy and undetectable viral load were associated with a greater number of normal cytology and undetected HPV DNA. Conclusion: The prevalence of cervical intraepithelial lesions in HIV-infected women is higher than in women without infection. The presence of HIV infection was the most important risk factor associated with the development of cervical lesions. (AU)

Introdução: O Papilomavírus Humano (HPV) é a infecção de transmissão sexual mais frequente na mulher. O HPV de alto risco oncogênico, associado a outros fatores, apresenta risco de evoluir para uma lesão pré-cancerosa do colo de útero e até mesmo para o câncer. Essa evolução está relacionada à persistência da infecção e outros fatores, principalmente os que interferem na imunidade da mulher. A imunossupressão causada pela infecção HIV é um fator importante para a persistência viral e o aparecimento destas lesões. Objetivos: Comparar a prevalência da infecção pelo HPV e das lesões intraepiteliais do colo de útero em mulheres HIV positivas e negativas, e descrever os possíveis fatores de risco associados. Métodos: A amostra foi composta por 50 mulheres HIV positivas (grupo de estudo) e 50 mulheres HIV negativas (grupo controle) recrutadas no sistema público de saúde de Florianópolis durante os meses de janeiro a abril de 2022. Foram coletadas amostras cervicais para análise citológica e para detecção do DNA HPV de alto risco oncogênico por reação em cadeia da polimerase (PCR). As variáveis categóricas foram comparadas pelo teste qui-quadrado, com nível de significância estabelecido em 5%. Resultados: A infecção pelo HPV foi mais prevalente no grupo controle, entretanto, as mulheres HIV positivas tiveram uma maior frequência de lesões intraepiteliais diagnosticadas na citologia. Os fatores como maior número de parceiros sexuais, depressão e tabagismo foram mais frequentes no grupo de mulheres HIV positivas. O número de células TCD4 inferior a 200 células/mm3 esteve associado a maior número de colpocitologias alteradas e teste DNA HPV positivo. O uso da terapia antirretroviral combinada e a carga viral indetectável estiveram associadas a um número elevado de citologias normais e DNA HPV não detectado. Conclusão: A prevalência de lesões intraepiteliais do colo do útero em mulheres infectadas pelo HIV foi maior que em mulheres soronegativas. A presença de infecção pelo HIV foi o fator de risco mais importante associado ao desenvolvimento de lesões cervicais.Palavras-chave: HPV. HIV. coinfecção. lesões intraepiteliais escamosas cervicais. prevalência.. (AU)

Assessment of the association between the frequency of micronucleus and p16INK4a/Ki-67 co-expression in patients with cervical intraepithelial lesions.

Human papilloma virus (HPV) infection is the main etiological factor for cervical intraepithelial lesions (CIN). An important characteristic of this process is the loss of genome stability. Therefore, it is imperative to use biomarkers of DNA damage caused by genomic instability to identify high risk individuals. We investigated the frequency of micronuclei (MN) in peripheral blood lymphocytes (PBL) of 20 patients, diagnosed as histologically CIN 1 and 10 healthy controls. We also examined the frequency of other nuclear anomalies including nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) in PBL of patients with CIN 1 and healthy controls, and evaluated the benefits of p16INK4a and Ki-67 (p16INK4a/Ki-67) immunohistochemical double staining for identifying cervical squamous cells that express HPV E6/E7 oncogenes. We analyzed the association between the frequency of MN in PBL and the amount of p16INK4a/Ki-67 co-expression in CIN 1 patients to establish genomic instability. Among CIN 1 subjects, 15% exhibited diffuse p16INK4a/Ki-67 co-expression and were considered high positive, 25% of the CIN 1 cases exhibited p16INK4a/Ki-67 co-expression restricted to the lower part of the epithelium and were considered low positive and the remaining 60% of cases were negative. The frequency of MN, NPBs and NBUDs differed significantly among groups. We found a statistically significant positive correlation between p16INK4a/Ki-67 co-expression and the frequency of MN, NPBs and NBUDs in PBL. Our findings demonstrate the efficacy of p16INK4a/Ki-67 double immunostaining for histological samples with CIN 1. MN frequency in PBL might be useful for detecting genomic instability in cases of HPV infection and CIN.