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OBJETIVO: Presentar un análisis relacional de cómo mujeres diagnosticadas con el virus del papiloma humano (VPH), displasia del cuello del útero o neoplasias del cuello uterino, reciben y/o acceden a la información y cómo la viven en sus relaciones cercanas. MATERIAL Y MÉTODOS: En 2008 se realizaron 34 entrevistas cualitativas a mujeres en dos clínicas de colposcopía de la Secretaría de Salud, en Hermosillo, Sonora. El análisis se basó en la teoría fundamentada. RESULTADOS: Existe una franca analogía entre cáncer cervicouterino (CaCu) y muerte, una amplia desinformación sobre VPH y displasias y una práctica persistente entre los médicos de no ofrecer información oportuna y clara a las pacientes. Existe una apreciación estigmatizante hacia la infección por VPH que afecta las relaciones cercanas de las mujeres. CONCLUSIÓN: A pesar de la necesidad de las pacientes de obtener información, no la exigen al médico, lo que contribuye a su desconfianza y angustia.OBJECTIVE: To present a relational analysis of how women who are diagnosed with the human papilloma virus (HPV), cervical dysplasia or cervical neoplasia receive or seek information, and how they experience this process within their immediate relationships. MATERIALS AND METHODS: In 2008, 34 qualitative interviews were carried out with women at two Secretary of Health colposcopy clinics in Hermosillo, Sonora. Analysis was based on grounded theory. RESULTS: There is a patent analogy between cervical cancer and death, much disinformation about HPV and dysplasias, and a persistent lack of timely and clear information given to patients by doctors. There is a stigma attached to HPV infection which affects women's immediate relationships. CONCLUSION: Despite patients' need to obtain information, they do not demand it from their doctor, which contributes to their anguish and distrust.

Background:  Uptake of human papillomavirus (HPV) vaccine in the United States is slow, and the effectiveness of the vaccine has not been assessed in high-risk adolescent populations.Methods:  We conducted a longitudinal study of 1139 sexually active, inner-city adolescent women receiving the 3-dose quadrivalent (4vHPV) vaccine. Cervical and anal specimens collected semiannually were tested using an L1-specific polymerase chain reaction assay. Postvaccination incidence of 4vHPV vaccine and nonvaccine HPV types, and risk of cervical cytological abnormalities, were assessed in relation to time to completion of all 3 vaccine doses.Results:  Compared to vaccine naive women at enrollment, vaccinated women had significantly lower incidence rate ratios of cervical infection with HPV6/11/16/18 (0.2; 95% confidence interval [CI], .1-.4) and the related types HPV31 and HPV45 (0.4 [95% CI, .2-1.0] and 0.3 [95% CI, .1-.6], respectively), as well as significantly lower incidence rate ratios of anal infection with HPV6/11/16/18 (0.4; 95% CI, .2-.7). Notably, we observed higher risks of cervical HPV6/11/16/18 infection (hazards ratio [HR], 2.9; 95% CI, 1.0-8.0) and associated cytological abnormalities (HR, 4.5; 95% CI, .7-26.0) among women immunized at ≥15 years of age who took ≥12 months (vs <12 months) to complete the 3-dose regimen.Conclusions:  Among adolescents immunized at ≥15 years of age, a longer time to complete the 3-dose schedule was associated with an increased risk of anogenital HPV6/11/16/18 infection and an increased incidence of associated cervical cytological abnormalities. [ABSTRACT FROM AUTHOR]

Cervical neoplasia is one of the most prevalent malignant neoplasms worldwide. Ribonucleotide reductase 1 (RRM1) is thought to play an essential role in modulating the development and progression of cervical neoplasia. Two novel genetic polymorphisms, RRM1 −756T>C and −269 C>A, are significantly correlated with RRM1 expression. Some epidemiological studies have demonstrated that genetic variants play a crucial role in susceptibility to cervical cancer. The present study aimed to identify the genetic polymorphisms RRM1 −756T>C and −269 C>A in patients with cervical neoplasia and healthy controls. In total, 493 subjects, comprising 324 healthy controls and 169 patients with cervical neoplasia, were enrolled for this study. The allelic discrimination of the RRM1 −756T>C (rs11030918) and −269C>A (rs12806698) polymorphisms was assessed using the ABI StepOne™ real-time polymerase chain reaction system and analyzed using Software Design Specification (SDS), Version 3.0, software with TaqMan assays. The risk of cervical cancer was examined, revealing adjusted odds ratios and 95% confidence intervals of 1.25 [0.51, 3.08] and 1.09 [0.43, 2.78] for individuals with CC alleles of RRM1 −756T>C and for individuals with AA alleles of RRM1 −269C>A genetic polymorphisms, respectively, compared to individuals with wild-type RRM1 genetic polymorphisms. No significant genetic interaction effect was observed in susceptibility to cervical neoplasia, and no association was found between genetic polymorphisms and clinical statuses of invasive cervical cancer. The genetic polymorphisms RRM1 −756T>C and −269C>A may not be a factor for susceptibility to cervical neoplasia. [ABSTRACT FROM AUTHOR]

Little is known about the incidence and risk of cervical intraepithelial neoplasia (CIN) grade 3, adenocarcinoma in situ and invasive cervical cancer (CIN3+) among migrants living with HIV in a European setting. We assessed the cumulative incidence (CuI) and hazard ratio (HR) of CIN2+ and CIN3+ in a cohort of women living with HIV (WLWH) ( n = 893) identified from the Swedish national HIV register and HIV-negative women ( n = 205,842) identified from the Swedish Population Register, matched on region of birth and age. Data was collected between 1993 and 2011 by linking our cohort with the Swedish National Cervical Screening Registry, collecting all cytological and histological results since 1993. The CuI of CIN3+ was 13.1% [95% confidence interval (CI) 8.9-17.2] for WLWH and 2.1% (95% CI 2.0-2.2) for HIV-negative after 18 years of follow-up. WLWH had more than eight times higher, age and region of birth matched, risk of CIN3+ than HIV-negative (HR 8.8: 95% CI 6.9-11.3). WLWH born in the East region, dominated by Thai women, had a two times higher risk of CIN3+ compared with WLWH born in Sweden (HR 2.47: 95% CI 1.2-5.0), which remained after adjusting for immunosuppression. Our results showed a substantially increased risk of CIN3+ among WLWH, which differed depending on birth region. Early HIV diagnosis and attendance to cervical cancer screening, with focus on migrants, is of crucial importance to minimize the incidence of cervical intraepithelial neoplasia. [ABSTRACT FROM AUTHOR]

Aim of the study: To evaluate the diagnostic capacity of tele-cervicography for the detection of cervical neoplasia as an adjunctive test with Papanicolaou (Pap) smears. Material and methods: Pap smear and tele-cervicography were performed on each subject. Histologic results were obtained for all patients. Results: Of the 863 females who had a tele-cervigram, 252 (29.2%) had a positive result. Of the 60 histologically confirmed cases of high-grade squamous intraepithelial lesions (HSILs), 56 (93.3%) were detected by tele-cervicography, including 16 (26.7%) with a positive grade of 1 and 40 (66.7%) with a positive grade of 2. With the positive threshold of tele-cervicography set as any positive grade (P0 to P3), the overall sensitivity was 94.0% (95% CI: 88.0-97.3%), the specificity was 80.9% (95% CI: 80.0-81.5%), and the positive likelihood ratio was 4.94 (95% CI: 4.23-5.77) for the detection of HSILs or cancer. The combination of tele-cervicography with Pap smear testing for the detection of HSILs or cancer resulted in an increase in sensitivity from 84.6% (Pap only: cutoff = atypical squamous cells of undetermined significance or more severe) to 98.3% (Pap plus tele-cervicography: cutoff = P0 or more severe). Conclusions: The sensitivity of tele-cervicography was higher than that of cytology for the detection of cervical neoplasia, and combining the two tests increased the sensitivity. Tele-cervicography can be considered a useful complementary tool to cytology. [ABSTRACT FROM AUTHOR]

The CDKN1A gene product is a p53 downstream effector, which participates in cell differentiation, development process, repair, apoptosis, senescence, migration, and tumorigenesis. The objective of our study was investigated the importance of two polymorphisms in the CDKN1A gene, rs1801270 (31C>A) and rs1059234 (70C>T), for the development of cervical lesions in a Southeastern Brazilian population (283 cases, stratified by lesion severity, and 189 controls). CDKN1A genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and/or DNA sequencing. CDKN1A 31A allele presents a genetic pattern of protection for the development of high-grade cervical lesions (CC vs CA genotype: OR = 0.60; 95 % CI = 0.38-0.95; p = 0.029; CA+AA vs CC genotype: OR = 0.60; 95 % CI = 0.39-0.93; p = 0.021). Allele distributions of the CDKN1A 70C>T polymorphism were also different between the two study groups, with the CDKN1A 70T allele being less prevalent among cases. Moreover, the double heterozygote genotype combination 31CA-70CT decreases the chance of developing high-grade squamous intraepithelial lesion (HSIL) and cancer (OR = 0.55; 95 % CI = 0.32-0.93; p = 0.034) by 50 %, representing a protective factor against the development of more severe cervical lesions. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to investigate the association between Toll-like receptor 2 (TLR2) gene polymorphisms and human papillomavirus (HPV)-related cervical neoplasia in Korean women.Material and Methods: Peripheral blood samples collected from 127 patients with HPV-related cervical neoplasia and 175 healthy women were genotyped for the TLR2 -16934, +1350, intron1, and 3' untranslated region (UTR) polymorphisms using the polymerase chain reaction and restriction fragment length polymorphism method.Results: The TLR2 -16934 A/A, intron1 A/A, and +1350 T/C genotypes were more frequent in patients than in controls [odds ratio (OR) = 2.1, 95% CI = 1.302-3.475, p = 0.002; OR = 1.9, 95% CI = 1.168-3.169, p = 0.010; and OR = 1.9, 95% CI = 1.211-3.123, p = 0.006, respectively]. The frequencies of the TLR2 + 1350 C and 3'UTR G alleles were also higher in patients (OR = 2.0, 95% CI = 1.236-3.121, p = 0.004 and OR = 1.7, 95% CI = 1.005-3.076, p = 0.046, respectively). The genotype frequencies of TLR2 -16934 A/A and intron1 A/A increased with increasing oncogenic risk of the HPV genotype, as follows. low-risk type < high-risk type < HPV-16 and/or HPV-18 type (p = 0.008).Conclusions: Our study provides the first evidence that TLR2 gene polymorphisms are associated with high-risk type HPV-related cervical neoplasia and may play an important role in susceptibility to HPV infection. Further large-scale and functional studies are needed to confirm the role of TLR2 gene polymorphisms in HPV-related cervical neoplasia. [ABSTRACT FROM AUTHOR]

Background: Precursors to anal squamous cell carcinoma may be detectable through screening; however, the literature suggests that population-level testing is not cost-effective. Given that high-grade cervical neoplasia (CIN) is associated with an increased risk of developing anal cancer, and in light of changing guidelines for the follow-up and management of cervical neoplasia, it is worthwhile to examine the costs and effectiveness of an anal cancer screening program delivered to women with previously-detected CIN.Methods: A model of anal cancer screening and treatment was constructed, to estimate the cost-effectiveness of a population of CIN II/III+ women who were screened using anal cytology vs. one that received no anal cancer screening. Costs were based on Canadian estimates, and survival was based on estimates taken from the scientific literature. Effectiveness was measured in terms of life years gained (LYG) and quality-adjusted life years (QALYs). The model was run for 50 cycles, with each cycle representing one year.Results: Incremental cost (screened vs. unscreened) was $82.17 per woman in the model. Incremental effectiveness was 0.004 LYG, and was equivalent to zero in terms of QALY. An ICER of $20,561/LYG was calculated, while no meaningful incremental cost-effectiveness ratio (ICER) could be calculated for quality-adjusted survival.Conclusion: Our analysis suggests that anal cancer screening is cost-effective in terms of overall survival in women with a previous diagnosis of CIN II or CIN III as part of regular follow-up, but may not contribute meaningfully-different quality-adjusted survival due to the adverse effects of screening-related interventions. [ABSTRACT FROM AUTHOR]

HIV-infected women are at increased risk of cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC), but it has been difficult to disentangle the influences of heavy exposure to HPV infection, inadequate screening and immunodeficiency. A case-control study including 364 CIN2/3 and 20 ICC cases matched to 1,147 controls was nested in the Swiss HIV Cohort Study (1985-2013). CIN2/3 risk was significantly associated with low CD4+ cell counts, whether measured as nadir [odds ratio (OR) per 100-cell/μL decrease = 1.15, 95% CI: 1.08, 1.22], or at CIN2/3 diagnosis (1.10, 95% CI: 1.04, 1.16). An association was evident even for nadir CD4+ 200-349 versus ≥350 cells/μL (OR = 1.57, 95% CI: 1.09, 2.25). After adjustment for nadir CD4+, a protective effect of >2-year cART use was seen against CIN2/3 (OR versus never cART use = 0.64, 95% CI: 0.42, 0.98). Despite low study power, similar associations were seen for ICC, notably with nadir CD4+ (OR for 50 vs. >350 cells/μL= 11.10, 95% CI: 1.24, 100). HPV16-L1 antibodies were significantly associated with CIN2/3, but HPV16-E6 antibodies were nearly exclusively detected in ICC. In conclusion, worsening immunodeficiency, even at only moderately decreased CD4+ cell counts, is a significant risk factor for CIN2/3 and cervical cancer. [ABSTRACT FROM AUTHOR]

Background: In the past, cervical cancer has been linked to Human Papilloma Virus (HPV) infection. Previously, we found that pre-neoplastic breast and ovarian lesions may be associated with lamin A/C deficiency, resulting in abnormal nuclear morphologies and chromosomal instability. Ultimately, these phenomena are thought to lead to cancer. Here, we assessed lamin A/C deficiency as an indicator for the risk to develop cervical cancer. Methods: The expression of lamin A/C was assessed by Western blotting in cervical uterine smears (CUS) of 76 adult women from Benin concomitant with nuclear morphology assessment and HPV genotyping using microscopy and PCR-based assays, respectively. In vitro analyses were performed to uncover the mechanism underlying lamin A/C expression alterations observed in vivo. The presence of cervical intra-epithelial neoplasia (CIN) was assessed by colposcopy. Results: Normal lamin A/C expression (group A) was observed in 39 % of the CUS, weak lamin A/C expression (group B) was observed in 28 % of the CUS and no lamin A/C expression (group C) was observed in 33 % of the CUS tested. Infection with oncogenic HPV was found to be significantly higher in group C (36 %) than in groups A (17 %) and B (14 %). Two years after our first assessment, CIN was observed in 20 % of the women in group C. The in vitro application of either a histone deacetylase inhibitor (trichostatin) or a protein kinase inhibitor (staurosporine) was found to restore lamin A/C expression in cervical cancer-derived cells. Conclusion: Lamin A/C deficiency may serve as an independent risk factor for CIN development and as an indicator for preventive therapy in cervical cancer. [ABSTRACT FROM AUTHOR]

High-risk human papillomavirus (HR-HPV) persistent infection is responsible for the development of the majority of cervical cancers. The therapy against HPV-associated cancer requires knowledge of the viral gene expression mechanisms. In this study, the polyadenylated polycistronic transcripts containing full-size E1 ORF and produced from the early P14 promoter were detected for the first time in cervical tumors with episomal forms of the HPV16 genome. P14-initiated mRNAs were revealed also in precancerous lesions. The amount of P14-initiated transcripts was significantly less compared to transcripts initiated from the major P97 HPV16 promoter in cervical intraepithelial neoplasms and squamous cell carcinomas. The ratios of P97/P14-transcripts determined by qRT-PCR were unique for each clinical sample and varied in quite wide ranges independent of disease progression stages or tumor grade. These data suggest that the levels of P14- and P97-transcripts are regulated independently from each other in cervical neoplasms. [ABSTRACT FROM AUTHOR]

Objective: Establishing the prevalence of premalignant and malignant cervical lesions amongst women living in the CARMEN initiative demonstration area, Bucaramanga, Colombia. Methodology: A cross-sectional study of 8,015 randomly selected women. Patients having abnormal cytology results received individualised diagnosis/treatment (colposcopy, biopsy, or conisation). Histopathological findings were correlated with demographical data and their sexual and reproductive history. Results: 8,071 women answered the survey but only 2,698 had up-to-date Pap smears (34.9%; 95%CI 17.2%-29.8%); 1,660 accepted updating their smears. 2.2% (95%CI 1.8%-2.6%) had Pap smears positive for cervical lesions, this being higher in those living with more mature women. Pre-malignant and malignant cervical lesion prevalence was 1.1% (95%CI 0.8%-1.4%). Women with pre-malignant or malignant cervical lesions were younger, had begun their sexual intercourse earlier and had had more sexual partners than healthy women. Conclusions: Pre-malignant and malignant cervical lesion prevalence is higher than in other parts of the world. Pap smear coverage is very low. Early detection of cervical cancer must be intensified.Objetivo: Establecer la prevalencia de lesiones premalignas y malignas entre las mujeres que viven en el área demostrativa de la iniciativa CARMEN de Bucaramanga, Colombia. Metodología: Estudio trasversal de 8.015 mujeres seleccionadas al azar. Las pacientes con citología anormal fueron estudiadas y tratadas de manera individualizada según un protocolo que incluía colposcopia, biopsia o conización. Se hizo correlación histopatológica con las variables sociodemográficas y la historia sexual y reproductiva Resultados: 8.071 mujeres contestaron la encuesta, pero solo 2.698 tenía una citología reciente (34,9%; IC 95% 17,2%-29,8%); 1.660 actualizaron su citología. 2,2% de estas fueron positivas, siendo más alta entre las mujeres que viven con otras mujeres adultas. La prevalencia de lesiones premalignas y malignas del cuello uterino fue 1,1% (IC 95% 0,8%-1,4%). Las mujeres con lesiones cervicales premalignas o malignas eran más jóvenes, habían iniciado relaciones sexuales más temprano y habían tenido más compañeros sexuales que las mujeres sanas. Conclusiones: La prevalencia de lesiones cervicales premalignas y malignas es superior a la que se informa en otras partes del mundo, mientras que la cobertura de citología cérvicovaginal es muy baja. Es necesario intensificar las actividades que buscan la detección temprana de cáncer cervical.

In the last two decades, the cervical cancer puzzle has become a coherent description that includes the identification of human papillomavirus (HPV) as the sexually transmitted etiologic agent and the characterization of the major determinants of HPV acquisition. Triage studies have consistently shown that HPV testing is more sensitive that repeated cytology in identifying underlying high-grade lesions in women with atypical scamous cells of undetermined significance (ASCUS). Studies that reflect primary screening conditions have shown that the sensitivity of HPV tests is higher than standard cytology in detecting high-grade lesions whereas the specificity is similar only in women aged 30-35 and above. HPV vaccines have an intrinsic attraction as a preventive strategy in populations with limited resources. However, vaccines designed to widespread use are still in development and testing phases. Time is ripe for exploring in depth the clinical implications of current achievements and to devise novel strategies for the prevention of cervical cancer.En las ultimas dos décadas, el enigma del cáncer cervical (CaCu) ha comenzado a ser dilucidado y actualmente se ha identificado a la infección por virus de papiloma humano (VPH) como su agente etiológico transmitido sexualmente, y se han caracterizado los principales determinantes de infección por VPH. Estudios epidemiológicos han mostrado consistentemente que las pruebas de determinación de ADN de VPH son más sensibles que la citología repetida para la identificación de lesiones de alto grado en mujeres con diagnóstico de células escamosas atípicas de significado indeterminado (ASCUS). Diversos estudios que evalúan el tamizaje primario en CaCu, han mostrado que la sensibilidad de las pruebas de VPH es más alta que la citología estándar para detectar lesiones de alto grado, donde la especificidad es similar sólo en mujeres con edades entre 30 y 35 años o mayores. Las vacunas de VPH tienen una atracción intrínseca como una estrategia preventiva en poblaciones con recursos limitados, sin embargo, el diseño de vacunas para uso generalizado están en fase de desarrollo y prueba. Actualmente, se deben de desarrollar investigaciones que exploren las implicaciones clínicas de la puesta en práctica de nuevas estrategias para la prevención de CaCu.

Objectives: We investigated HPV genotypes in a large cohort of patients with definitive cervical histologic diagnosis., Methods: HPV testing was performed by real-time PCR assay, including 18 high-risk HPV (hrHPV) and 3 low-risk HPV (lrHPV). Totally 61,422 patients with documented HPV genotyping results within 6 months before cervical histologic diagnoses were included., Results: HrHPV positive rate was 55.1% among all tested cases with the highest in adenosquamous carcinoma (94.1%), followed by squamous cell carcinoma (SCC) (93.7%), cervical intraepithelial neoplasia 2/3 (CIN2/3) (92.8%). HrHPV positive rates were significantly higher in high-grade squamous lesions than in those in glandular lesions. HPV16 was the most common genotype followed by HPV52 and HPV58 in CIN2/3. The most frequent hrHPV genotype in adenocarcinoma in situ (AIS) was HPV18, followed by HPV16, HPV45 and HPV52. In SCC cases, HPV16 was the most common type followed by HPV58, HPV52, HPV18 and HPV33. However, HPV18 showed significantly higher prevalence in adenocarcinoma and adenosquamous carcinoma than in that in SCC. Theoretically, the protective rates of 2/4-valent and 9-valent vaccine were 69.1% and 85.8% for cervical cancers., Conclusions: The prevalence of HPV genotypes in Chinese population was different from that in Western population. Some hrHPV types were identified in cervical precancerous lesions and cancers, which are not included in current HPV vaccines. These data provide baseline knowledge for future HPV vaccine development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhong, Li, Sun, Xiao, Li, Zhou, Cong, Sui, Tao and Zhao.)

Objetivos: comparar o desempenho das amostras do canal cervical e fundo de saco vaginal para o exame colpocitológico no diagnóstico da neoplasia do colo uterino. Métodos: foram constituídos três grupos seqüenciais: grupo 1) 10.048 mulheres com amostras da ectocérvice e fundo de saco, utilizando espátula de Ayre; grupo 2) 3.847 mulheres com amostras da ectocérvice, fundo de saco e canal cervical, utilizando espátula de Ayre e escova cytobrush; grupo 3) 4.059 mulheres com amostras da ectocérvice e canal cervical, utilizando espátula de Ayre e escova cytobrush. A metodologia estatística utilizou análise de variância (ANOVA) e comparação de proporções. Resultados: os percentuais de exames alterados dos grupos 2 (2,6%) e 3 (2,4%), incluindo todas as lesões escamosas e glandulares, foram significativamente maiores que no grupo 1 (2%). Os percentuais de diagnóstico da lesão intra-epitelial escamosa de baixo grau (LIE-BG) não foram estatisticamente diferentes entre os três grupos (1,27; 1,25 e 1,07%). Por outro lado, os percentuais de diagnóstico da lesão intra-epitelial escamosa de alto grau (LIE-AG) foram significativamente maiores nos grupos 2 (0,81%) e 3 (0,77%) do que no grupo 1 (0,54%). A diferença entre os percentuais dos grupos 2 e 3 não foi estatisticamente significante. Conclusões: a amostra do canal cervical melhora o desempenho do exame colpocitológico para o diagnóstico da lesão intra-epitelial escamosa de alto grau, ao passo que a amostra de fundo de saco não interfere significativamente nos percentuais de diagnóstico das lesões intra-epiteliais.Purpose: to compare the performance of cervical canal and vaginal cul-de-sac samples for colpocytology testing, in order to diagnose cervical neoplasia. Methods: three sequential groups were constituted: group 1 - 10,048 women with ectocervix and cul-de-sac samples collected with the use of an Ayre spatula; group 2 - 3,847 women with ectocervix, cul-de-sac and cervical canal samples taken with an Ayre spatula and a cytobrush, and group 3 -- 4,059 women with ectocervix and cervical canal samples, using an Ayre spatula and a cytobrush. ANOVA (analysis of variance) and comparison of proportions were utilized for the statistical analysis. Results: the rates of abnormal tests in groups 2 (2.6%) and 3 (2.4%), including all squamous and glandular lesions, were significantly higher than in group 1 (2.0%). The diagnosis rates of low-grade squamous intraepithelial lesion (LGSIL) were not statistically different between the three groups (1.27, 1.25 and 1.07%). On the other hand, the diagnosis rates of high-grade squamous intraepithelial lesion (HGSIL) were statistically higher in groups 2 (0.81%) and 3 (0.77%) than in group 1 (0.54%). The difference between the rates of the second and the third groups did not present any statistical significance. Conclusions: the cervical canal sampling improves the performance of cytologic testing for the diagnosis of HGSIL, while cul-de-sac sampling does not change significantly the performance in diagnosing cervical neoplasia.

Objetivos: avaliar a utilização da conização por cirurgia de alta freqüência por alça (CAF) na neoplasia intra-epitelial cervical (NIC), a importância do comprometimento das margens de ressecção e o seguimento das pacientes. Métodos: foram avaliadas 95 mulheres submetidas à CAF por NIC entre janeiro de 1996 e dezembro de 1997. Para análise estatística, utilizamos o coeficiente de concordância kappa e o teste de tendência de Cochran Armitage. Resultados: dos 63 casos submetidos à biópsia dirigida antes da conização, o cone por CAF apresentou lesões mais graves que a biópsia em 24 casos, sendo um caso microinvasor, e em 8 mulheres a biópsia eliminou a lesão. Entre as pacientes submetidas à conização com biópsia prévia compatível com cervicite ou NIC 1, 14/25 (56%) apresentavam NIC 2 ou 3. Das 32 mulheres que não tinham biópsia prévia, 15 apresentavam NIC 2 ou 3, e quatro, carcinoma microinvasor no cone. Em relação às margens do cone, 25 casos (26%) apresentaram margens endocervicais comprometidas e quanto maior o grau da lesão cervical maior a possibilidade de presença de lesão nas margens (p = 0,024). Dessas pacientes, 2 de 10 submetidas a novo procedimento apresentavam doença residual na peça cirúrgica. Entre as 70 pacientes com margens livres foram realizadas três conizações a frio e uma histerectomia e duas apresentavam doença residual na peça cirúrgica. Conclusões: a conização por CAF sem biópsia prévia depende da combinação entre o diagnóstico citológico e a experiência do colposcopista e, em princípio, deve ser reservada para os casos em que a colpocitologia e a colposcopia são concordantes e compatíveis com NIC 2 ou 3. Por outro lado, a ampliação cirúrgica pós-CAF no tratamento da NIC não é determinada exclusivamente pelo comprometimento das margens, mas sim pelo seguimento, excluindo-se os casos de microinvasão e lesões glandulares que se beneficiam com a avaliação histológica posterior.Purpose: to evaluate conization by the loop electrosurgical excision procedure (LEEP) for the diagnosis and treatment of cervical intraepithelial neoplasms (CIN), the importance of the margins and follow-up of these women. Methods: 95 women who underwent conization by LEEP for CIN and microinvasive carcinoma from January 1996 to December 1997 were evaluated. For statistical analysis, we used the kappa agreement coefficient and the tendency test of Cochran Armitage. Results: among 63 cases who underwent colposcopically directed biopsy before the conization, the cone presented the same grade of lesion in 20 and no residual disease in 8. The cone lesion presented a higher grade in 24 cases and one of them was a microinvasive carcinoma. Among the 25 women who underwent the cone biopsy with a previous biopsy suggestive of cervicitis or CIN 1, 56% had CIN 2 or 3 in the cone. Among the 32 women without previous biopsy, 15 had CIN 2 or 3, and four had microinvasive carcinoma in the cone. Regarding the margins of the cone, 25 cases presented some grade of CIN in the endocervical margins and 2/10 who underwent a second procedure presented residual disease on histological analysis. Among the 70 women with free cone margins, 2/4 who underwent a second procedure had residual disease on histological analysis. Conclusion: conization by LEEP without previous directed biopsy depends on the experience of the colposcopist. The second resection after LEEP for the diagnosis and treatment of CIN depends not only on the presence of disease in the cone margins but also on the follow-up. A second histological analysis is recommended in cases with microinvasive carcinoma and glandular lesion and affected margins.

Cervical cancer development has been mainly associated with persistent human papillomavirus (HPV) infections. However, HPV infection is unlikely to be sufficient to cause cervical cancer, and the contribution of other sexually transmitted infections (STIs) could be the determining factor for cervical lesion-progression. The aim of this study was to estimate the prevalence of STIs associated with HPV-positivity in 201 cervical samples from patients who underwent annual routine gynecological exams. The overall prevalence of STIs was 57.7%, and the most frequent infection was Ureaplasma spp (UP) (39.8%), followed by Gardnerella vaginalis (GV) (25.9%), α-HPV (18.4%), Chlamydia trachomatis (CT) (1.5%), and Mycoplasma genitalium (MG) (0.5%). The highest prevalence rate of multiple non-HPV infections was observed for the age-range 31-40; for papillomavirus infection, the age-range was 21-30. In normal cervical samples, HPV16 was the most prevalent genotype (24.3%), followed by genotypes 58 (13.5%) and 52 (10.8%). Intriguingly, HPV18 was not detected in the study population, and genotypes 52 and 58 were found exclusively in samples with abnormal cytology. Papillomavirus infection with oncogenic types was significantly associated with GV ( P = 0.025) and strongly associated with multiple non-HPV pathogens ( P = 0.002). The following variables correlated significantly with cytological diagnosis of low-grade squamous intraepithelial lesion (LSIL): GV ( P = 0.028), multiple non-HPV infections ( P = 0.001), and high-risk HPV positivity ( P = 0.001). Epidemiological data from this study will contribute to the molecular detection of sexually transmitted pathogens from screening programs to identify those women who are at risk for developing cervical lesions. J. Med. Virol. 87:2098-2105, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The purpose of this paper is to critically examine the literature and present a comprehensive model of three pathways through which IPV increases the risk for cervical cancer. The first pathway is increased exposure to cervical cancer risk factors among IPV victims, including smoking, psychosocial stress, risky sexual behaviors, and sexually transmitted infections (STDs/STIs), particularly human papillomavirus infection. The second pathway is poor compliance with cervical cancer screening. The third pathway is delay/discontinuation in treatment for cervical dysplasia and neoplasia. Control imposed by the abusive partner, competing life priorities, and limited access to financial/support resources restrict a woman's ability to seek cancer services. Higher rates, severity, and duration of IPV among low-income, Black, and Hispanic women may explain the pervasive cervical cancer disparities. [ABSTRACT FROM AUTHOR]

Background: Parity is well established as a risk factor for cervical cancer. It is not clear, however, how pregnancy influences the natural history of HPV infection and cervical neoplasia. Our objective was to study the risk of HPV infection and cervical squamous intraepithelial lesions (SIL) after pregnancy.Methods: We used the Ludwig-McGill cohort study which includes 2462 women recruited in Sao Paulo, Brazil in 1993-97 and followed for up to 10 years. Cellular specimens were collected every 4-6 months for Pap cytology and HPV detection and genotyping by a polymerase chain reaction protocol. Study nurses recorded pregnancy occurrence during follow-up. HPV and Pap results from pregnant women were available before and after, but not during pregnancy. The associations between pregnancy and post-partum HPV infection/SIL were studied using generalized estimating equation models with logistic link. Adjusted odds ratios (OR) were estimated with empirical adjustment for confounding.Results: We recorded 122 women with a history of pregnancy during follow-up. Of these, 29 reintegrated the cohort study after delivery. No association between HPV and pregnancy was found. A single SIL case (high grade SIL) occurred post-partum. Likewise, there was no association between pregnancy and risk of low grade SIL or any-grade SIL at the next visit (adjusted OR = 0.84, 95 % CI: 0.46-15.33) after controlling for confounders.Conclusions: No associations were found between pregnancy and HPV or LSIL. The single observed case of HSIL post-partum was more than would be expected based on the rate of these abnormalities among non-pregnant women. As this association was found with only one case, caution is required in the interpretation of these results. [ABSTRACT FROM AUTHOR]

Epigenetic alterations of human papillomavirus (HPV) genome play an important role in virus life cycle and carcinogenic progression. The aim of the current study was to investigate the correlation between the grade of cervical pathology and DNA methylation status within the L1 gene and the long control region (LCR) of HPV16, HPV18 and HPV51. HPV genomes were analyzed using bisulfite DNA modification procedure with the subsequent amplification of target DNA regions and sequencing. A collection of 202 cervical specimens was analyzed: 157 HPV16-positive specimens, 21 HPV18-positive specimens and 24 HPV51-positive specimens. This study revealed that methylation of CpG was significantly more prevalent in L1 gene as compared to LCR region of all three studied HPV types and the degree of DNA methylation level correlated with the severity of cervical neoplasia. An increased DNA methylation level of HPV16 promoter region in case of cervical cancer was determined. [ABSTRACT FROM AUTHOR]

Background: Pathological classification of cervical intraepithelial neoplasia (CIN) is problematic as it relies on subjective criteria. We developed an imaging method that uses spectroscopy to assess the fluorescent intensity of cervical biopsies derived directly from hematoxylin and eosin (H&E) stained tissues. Methods: Archived H&E slides were identified containing normal cervical tissue, CIN I, and CIN III cases, from a Community Hospital and an Academic Medical Center. Cases were obtained by consensus review of at least 2 senior pathologists. Images from H&E slides were captured first with bright field illumination and then with fluorescent illumination. We used a Zeiss Axio Observer Z1 microscope and an AxioVision 4.6.3-AP1 camera at excitation wavelength of 450-490 nm with emission captured at 515-565 nm. The 32-bit grayscale fluorescence images were used for image analysis. Results: We reviewed 108 slides: 46 normal, 33 CIN I and 29 CIN III. Fluorescent intensity increased progressively in normal epithelial tissue as cells matured and advanced from the basal to superficial regions of the epithelium. In CIN I cases this change was less prominent as compared to normal. In high grade CIN lesions, there was a slight or no increase in fluorescent intensity. All groups examined were statistically different. Conclusion: Presently, there are no markers to help in classification of CIN I-III lesions. Our imaging method may complement standard H&E pathological review and provide objective criteria to support the CIN diagnosis. [ABSTRACT FROM AUTHOR]

Background: The association between hormonal contraception and cervical cancer is controversial. These controversies may hamper the uptake of hormonal contraceptives. Objective: To determine the association between hormonal contraceptives and cervical neoplasia. Materials and methods: This was a case-control study in which Pap-smear results of 156 participants on hormonal contraceptives were compared with those of 156 participants on no form of modern contraception. Modern contraception is defined as the use of such contraceptives as condoms, pills, injectables, intrauterine devices, implants, and female or male sterilization. Those found to have abnormal cervical smear cytology results were subjected further to colposcopy. Biopsy specimens for histology were collected from the participants with obvious cervical lesions or those with suspicious lesions on colposcopy. The results were analyzed with descriptive and inferential statistics at a 95% level of confidence. Results: A total of 71 (45.5%), 60 (38.5%), and 25 (16.0%) of the participants on hormonal contraceptives were using oral contraceptives, injectable contraceptives, and implants, respectively. Cervical neoplasia was significantly more common among participants who were ≥35 years old (6% versus 1%, P<0.0001), rural dwellers (6% versus 3.5%, P<0.0001), unmarried (7.6% versus 3.5%, P<0.0001), unemployed (6.8% versus 3.5%, P<0.0001), less educated (6% versus 3.8%, P<0.0001), and had high parity (6.8% versus 3.6%, P<0.0001). There was no statistical significant difference in cervical neoplasia between the two groups of participants (7 [4.5%] versus 6 [3.8%], P=1.0). Conclusion: There was no association between hormonal contraceptives and cervical neoplasia in this study. [ABSTRACT FROM AUTHOR]

Background: Evidence suggests that Human Immunodeficiency Virus (HIV) infection is a risk factor for preinvasive and invasive lesions of cervix but confusion regarding pathogenesis and progression of cervical neoplasia in HIV-positive women still prevails. Aims: To find the incidence of cervical neoplasia in HIV positive and HIV-negative women and to study the impact of CD4 counts, duration of HIV infection, and treatment with highly active antiretroviral therapy (HAART) on the incidence of cervical lesions in HIV positive women. Materials and Methods: It was an observational case control study carried over a period of one year at the Department of Obstetrics and Gynaecology and Department of Medicine, King George Medical University, Lucknow. Cases were HIV-positive women and controls were HIV negative women. Those with previous diagnosis or treatment for cervical neoplasia, history of total hysterectomy or coexistent immunosuppressive conditions were excluded. All subjects had cervical screening by Pap smear. Colposcopy and cervical biopsy were done if indicated. Statistical Analysis Used: Chi square test, univariate, and multivariate analysis. Results: The incidence of cervical lesions in HIV-positive women (159.66 per 1000 screened women) was higher compared to HIV-negative women (15.15 per 1000 screened women) (P < 0.001). CD4 counts less than 500/mm3 were associated with an increased incidence of cervical neoplasia (P < 0.00I). The incidence of cervical lesions in HIV-positive women on HAART was 16.16% as compared to 15% in HIV-positive women not on HAART. Duration of HIV infection more than 2 years was associated with an increased incidence of cervical lesions in univariate analysis (P < 0.001). Conclusions: Seropositivity is associated with an increased incidence of cervical lesions. This risk is further enhanced by CD4 counts less than 500/mm3 and duration of HIV infection of more than two years. [ABSTRACT FROM AUTHOR]

Cervical cancer is the fourth most common cause of mortality worldwide. Persistent infection with high-risk human papillomaviruses (hrHPV) is a known significant risk factor in cervical neoplasia development (CN). Though HPV contributes to carcinogenesis, other factors provide an ideal niche for persistence of HPV, especially, coinfection with Chlamydia trachomatis (CT) which has been linked to CN development. CT infection is associated with inflammation, cell proliferation, EMT transition and anti-apoptotic processes. To better understand the correlation between HPV-CT coinfection and CN development, a literature review was conducted on the prevalence of HPV-CT coinfection focusing on the role of infection-induced inflammation as HPV-CT coinfection creates an environment for cellular transformation, activates an innate immune response and triggers EMT transition. Moreover, inflammation plays a crucial role in developing neoplasia as there is a decrease in effector cells and a change in the levels of players like ROS and miRs. CT infection induces chronic inflammation followed by cervical epithelial cell damage and increases susceptibility to HPV infection which may lead to cellular transformation. The literature search was performed based on a comprehensive investigation of publications in the PubMed journal database and Scopus, on the development of CN. We have reviewed the prevalence of HPV-CT infection and the factors increasing the risk of developing CN. • Chlamydia trachomatis infection may increase the persistence of HPV. • Prevalence of HPV- Chlamydia trachomatis coinfection is higher in younger women. • HPV-CT coinfection creates an environment for cellular transformation. [ABSTRACT FROM AUTHOR]

We investigated the importance of two adjacent functional polymorphisms in the Murine Double Minute 2 ( MDM2) gene, SNP285 G > C and SNP309 T > G, for the development of cervical lesions in a Southeastern Brazilian population (293 cases and 184 controls). MDM2 genotyping was performed by PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism) and/or DNA sequencing. MDM2 SNP309 has potential as a biomarker of cervical neoplasia in non-smokers, patients with family history of cancer, or those who had late sexual debut (>16 years). Besides, this polymorphism may help identify women at risk of developing severe cervical lesion at a young age (<30 years). [ABSTRACT FROM AUTHOR]

Background: Hospital-based registries are important tools for policy formulations and region-specific data creation, particularly in case of cervical cancer, which is preventable by an effective screening program. Objective: To study the epidemiological characteristics and trends in cervical neoplasia in an urban population over a decade. Materials and Methods: Data were collected from the histopathological records of patients from January 2000 to December 2009. Results: A total of 1315 gynecological malignancies were reported with cancer cervix being the most common (70.4%) with a progressive increase in the number from 56 in 2000 to 157 in 2009. Squamous cell cancer was the predominant variant with majority in advanced stage. The mean age was 50.1 years with doubling of cases in the ≤35-year category. Of 742 colposcopic biopsies performed, cervical intraepithelial neoplasia (CIN) 1 was diagnosed in 34.9%, CIN 2 in 11.8%, CIN 3 in 7.8%, and microinvasive cancer in 0.8% cases. Conclusion: Though screening programs are in place, their effectiveness can be judged only by such reporting systems that aid in modifying the current cancer control strategies. [ABSTRACT FROM AUTHOR]

Background A community-based randomized trial was conducted in Costa Rica to evaluate the HPV-16/18 AS04-adjuvanted vaccine ( NCT00128661 ). The primary objective was to evaluate efficacy of the vaccine to prevent cervical intraepithelial neoplasia 2 or more severe disease (CIN2+) associated with incident HPV-16/18 cervical infections. Secondary objectives were to evaluate efficacy against CIN2+ associated with incident cervical infection by any oncogenic HPVs and to evaluate duration of protection against incident cervical infection with HPV-16/18. Vaccine safety and immunogenicity over the 4-year follow-up were also evaluated. Methods We randomized (3727 HPV arm; 3739 control arm), vaccinated (HPV-16/18 or Hepatitis A) and followed (median 53.8 months) 7466 healthy women aged 18–25 years. 5312 women (2635 HPV arm; 2677 control arm) were included in the according to protocol analysis for efficacy. The full cohort was evaluated for safety. Immunogenicity was considered on a subset of 354 (HPV-16) and 379 (HPV-18) women. HPV type was assessed by PCR on cervical specimens. Immunogenicity was assessed using ELISA and inhibition enzyme immunoassays. Disease outcomes were histologically confirmed. Vaccine efficacy and 95% confidence intervals (95%CI) were computed. Results Vaccine efficacy was 89.8% (95% CI: 39.5–99.5; N = 11 events total) against HPV-16/18 associated CIN2+, 59.9% (95% CI: 20.7–80.8; N = 39 events total) against CIN2+ associated with non-HPV-16/18 oncogenic HPVs and 61.4% (95% CI: 29.5–79.8; N = 51 events total) against CIN2+ irrespective of HPV type. The vaccine had an acceptable safety profile and induced robust and long-lasting antibody responses. Conclusions Our findings confirm the high efficacy and immunogenicity of the HPV-16/18 vaccine against incident HPV infections and cervical disease associated with HPV-16/18 and other oncogenic HPV types. These results will serve as a benchmark to which we can compare future findings from the ongoing extended follow-up of participants in the Costa Rica trial. Trial registration : Registered with clinicaltrials.gov: NCT00128661 . [ABSTRACT FROM AUTHOR]

Background: The importance of human papillomavirus (HPV) viral load in the pathogenesis of cervical cancer among HIV-infected and HIV-uninfected women has not yet been established. Methods: In this cross-sectional study, HPV-16 viral loads were measured using previously-collected and frozen cervical swab samples from 498 HPV-16 positive Senegalese women (368 HIV-seronegative, 126 HIV-1 and/or HIV-2 seropositive). The real-time polymerase chain reaction assay was used to quantify HPV-16 E7 copy number normalized by human cellular DNA (β-actin), and viral loads were log10 transformed. Associations between HPV-16 viral load, degree of cervical abnormality, and HIV status were assessed using multinomial and linear regression methods. Results: Compared to women with normal cytology, the likelihood of CIN1 (ORa: 1.21, 95% CI 0.93-1.57), CIN2-3 (ORa: 2.38, 95% CI 1.72-3.29) and cancer (ORa: 2.12, 95% CI 1.52-2.96) was found to increase for each 1-unit log10 increase in HPV-16 viral load. Compared to HIV-negative women, HIV-positive women had higher average HPV-16 viral load values (βa: 0.39, 95% CI 0.03-0.75), even after accounting for degree of cervical abnormality. Conclusion: In our study of women including those with cancer, HPV-16 viral load was associated with a higher likelihood of cervical abnormalities. However, substantial overlaps across categories of disease severity existed. Higher viral load among HIV-infected individuals may indicate that HIV infection influences HPV viral replication factors. [ABSTRACT FROM AUTHOR]