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1.
Lancet Oncol ; 24(12): 1321-1333, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37949086

RESUMO

BACKGROUND: To meet global cervical cancer elimination efforts, a wider range of affordable and accessible vaccines against human papillomavirus (HPV) are needed. We aimed to evaluate the immunogenicity and safety of a quadrivalent HPV vaccine (targeting HPV types 6, 11, 16, and 18), developed and manufactured by the Serum Institute of India (SIIPL). Here we report outcomes in the 9-14 years cohort. METHODS: This randomised, active-controlled, phase 2/3 trial was conducted at 12 tertiary care hospitals across India. Healthy participants aged 9-14 years or 15-26 years with no history of HPV vaccination were eligible for enrolment. Female participants were randomly assigned (1:1) with an interactive web response system, by use of a central computer-generated schedule and block randomisation (block sizes of 2, 4, 6, and 8), to receive the SIIPL quadrivalent HPV vaccine (Cervavac; SIIPL, Pune, India) or the comparator quadrivalent HPV vaccine (Gardasil; Merck Sharp & Dohme, Harleem, the Netherlands). Participants, investigators, laboratory technicians, and sponsors were masked to treatment allocation of female participants. Male participants were given the SIIPL quadrivalent HPV vaccine in an open-label manner. Study vaccines were administered intramuscularly with a two-dose schedule (at day 0 and 6 months) in the cohort aged 9-14 years, and with a three-dose schedule (at day 0, month 2, and month 6) in the cohort aged 15-26-years. Immunogenicity was assessed 30 days after the last dose by use of multiplexed ELISA. The primary outcome was the non-inferiority of immune response in terms of the geometric mean titre (GMT) of antibodies against HPV types 6, 11, 16, and 18 generated by the SIIPL quadrivalent HPV vaccine in girls and boys (aged 9-14 years) compared with the GMT generated by the comparator quadrivalent HPV vaccine in women aged 15-26 years at month 7 in the modified per-protocol population (ie, all participants who received all doses of study vaccines per assigned treatment group and had both day 0 and 1-month immunogenicity measurements after the last dose following protocol-defined window periods with no major protocol deviations). Non-inferiority was established if the lower bound of the 98·75% CI of the GMT ratio was 0·67 or higher. The co-primary outcome of occurrence of solicited adverse events (within 7 days of each dose) and unsolicited adverse events (up to 30 days after the last dose) was assessed in all participants who were enrolled and received at least one dose of study vaccine. The trial is registered with the Clinical Trials Registry - India (CTRI/2018/06/014601), and long-term follow-up is ongoing. FINDINGS: Between Sept 20, 2018, and Feb 9, 2021, 2341 individuals were screened, of whom 2307 eligible individuals were enrolled and vaccinated: 1107 (738 girls and 369 boys) in the cohort aged 9-14 years and 1200 (819 women and 381 men) in the cohort aged 15-26 years. No race or ethnicity data were collected. 350 girls and 349 boys in the SIIPL quadrivalent HPV vaccine group and 338 women in the comparator vaccine group were included in the modified per-protocol population for the primary endpoint analysis. The median follow-up for the analyses was 221 days (IQR 215-231) for girls and 222 days (217-230) for boys in the SIIPL quadrivalent HPV vaccine group, 223 days (216-232) for girls in the comparator vaccine group, and 222 days (216-230) for women in the comparator vaccine group. GMT ratios were non-inferior in girls and boys receiving the SIIPL quadrivalent HPV vaccine compared with women receiving the comparator vaccine: GMT ratios for girls were 1·97 (98·75% CI 1·67-2·32) for HPV type 6, 1·63 (1·38-1·91) for HPV type 11, 1·90 (1·60-2·25) for HPV type 16, and 2·16 (1·79-2·61) for HPV type 18. For boys the GMT ratios were 1·86 (1·57-2·21) for HPV type 6, 1·46 (1·23-1·73) for HPV type 11, 1·62 (1·36-1·94) for HPV type 16, and 1·80 (1·48-2·18) for HPV type 18. The safety population comprised all 1107 participants (369 girls and 369 boys in the SIIPL quadrivalent HPV vaccine group, and 369 girls in the comparator group). Solicited adverse events occurred in 176 (48%) of 369 girls and 124 (34%) of 369 boys in the SIIPL vaccine group and 179 (49%) of 369 girls in the comparator vaccine group. No grade 3-4 solicited adverse events occurred within 7 days of each dose. Unsolicited adverse events occurred in 143 (39%) girls and 147 (40%) boys in the SIIPL vaccine group, and 143 (39%) girls in the comparator vaccine group. The most common grade 3 unsolicited adverse event was dengue fever, in one (<1%) girl in the SIIPL vaccine group and three (1%) girls in the comparator group. There were no grade 4 or 5 adverse events. Serious adverse events occurred in three (1%) girls and three (1%) boys in the SIIPL vaccine group, and five (1%) girls in the comparator vaccine group. No vaccine-related serious adverse events were reported. There were no treatment-related deaths. INTERPRETATION: We observed a non-inferior immune response with the SIIPL quadrivalent HPV vaccine in girls and boys aged 9-14 years and an acceptable safety profile compared with the comparator vaccine. These findings support extrapolation of efficacy from the comparator vaccine to the SIIPL quadrivalent HPV vaccine in the younger population. The availability of the SIIPL quadrivalent HPV vaccine could help meet the global demand for HPV vaccines, and boost coverage for both girls and boys globally. FUNDING: Biotechnology Industry Research Assistance Council, Department of Biotechnology (DBT), Government of India, and Serum Institute of India.


Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Humanos , Masculino , Feminino , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/epidemiologia , Índia , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/efeitos adversos , Colo do Útero , Papillomavirus Humano 6 , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Método Duplo-Cego , Anticorpos Antivirais
2.
J Am Chem Soc ; 145(43): 23503-23518, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37873979

RESUMO

In cells, the formation of RNA/DNA hybrid duplexes regulates gene expression and modification. The environment inside cellular organelles is heterogeneously crowded with high concentrations of biomolecules that affect the structure and stability of RNA/DNA hybrid duplexes. However, the detailed environmental effects remain unclear. Therefore, the mechanistic details of the effect of such molecular crowding were investigated at the molecular level by using thermodynamic and nuclear magnetic resonance analyses, revealing structure-dependent destabilization of the duplexes under crowded conditions. The transition from B- to A-like hybrid duplexes due to a change in conformation of the DNA strand guided by purine-pyrimidine asymmetry significantly increased the hydration number, which resulted in greater destabilization by the addition of cosolutes. By quantifying the individual contributions of environmental factors and the bulk structure of the duplex, we developed a set of parameters that predict the stability of hybrid duplexes with conformational dissimilarities under diverse crowding conditions. A comparison of the effects of environmental conditions in living cells and in vitro crowded solutions on hybrid duplex formation using the Förster resonance energy transfer technique established the applicability of our parameters to living cells. Moreover, our derived parameters can be used to estimate the efficiency of transcriptional inhibition, genome editing, and silencing techniques in cells. This supports the usefulness of our parameters for the visualization of cellular mechanisms of gene expression and the development of nucleic acid-based therapeutics targeting different cells.


Assuntos
Oligonucleotídeos , RNA , Oligonucleotídeos/química , RNA/química , Sequência de Bases , Conformação de Ácido Nucleico , DNA/química , Termodinâmica
3.
Asian Pac J Cancer Prev ; 24(10): 3495-3500, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37898855

RESUMO

AIM: To evaluate the feasibility and efficacy of switching to a self-sampling based screening as compared to ongoing provider-collection based screening using HPV DNA test and assess the compliance of HPV positive women for further treatment during the COVID 19 pandemic. METHOD: The study participants were women aged 30-60 years from rural and semi-urban communities around Kolkata, who underwent screening followed by HPV testing by Hybrid Capture II test. In the pre pandemic era, the women who attended the health centres where trained health workers that collected cervical samples. Following lockdown, the health workers distributed the self-sampling device to the women during home visits and counselled them to collect their samples by themselves. Thereafter the self collected screened positive women were brought to the hospital for further treatment instead of community clinics. RESULTS: From April 2018 to March 2020, 12,718 women underwent screening using either HPV DNA test or visual inspection with acetic acid. HPV samples were either provider collected (62.7%) or self-collected (37.2%). The HPV positivity and CIN2+ detection rate were 5.4% and 2%. From April 2020 to February 2022, 10,792 women underwent screening using self-sampling only. The HPV positivity rate and CIN2+ detection rate were found to be 5.1% and 1.9 % . CONCLUSION: Cervical cancer screening by HPV self-sampling advocates participation of more women especially in rural areas, while accelerating progress towards elimination of cervical cancer.


Assuntos
COVID-19 , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Masculino , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Pandemias/prevenção & controle , Detecção Precoce de Câncer , Papillomaviridae/genética , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/prevenção & controle , Controle de Doenças Transmissíveis , Programas de Rastreamento , Manejo de Espécimes , Esfregaço Vaginal
4.
Nucleic Acids Res ; 51(9): 4101-4111, 2023 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-36718808

RESUMO

RNA performs various spatiotemporal functions in living cells. As the solution environments significantly affect the stability of RNA duplexes, a stability prediction of the RNA duplexes in diverse crowded conditions is required to understand and modulate gene expression in heterogeneously crowded intracellular conditions. Herein, we determined the nearest-neighbor (NN) parameters for RNA duplex formation when subjected to crowding conditions with an ionic concentration relevant to that found in cells. Determination of the individual contributions of excluded volume effect and water activity to each of the NN parameters in crowded environments enabled prediction of the thermodynamic parameters and their melting temperatures for plenty of tested RNA duplex formation in vitro and in cell with significant accuracy. The parameters reported herein will help predicting RNA duplex stability in different crowded environments, which will lead to an improved understanding of the stability-function relationship for RNAs in various cellular organelles with different molecular environments.


Assuntos
Conformação de Ácido Nucleico , Estabilidade de RNA , RNA , RNA/química , RNA/genética , RNA/metabolismo , Temperatura , Termodinâmica , Água/química , Água/metabolismo
5.
Cytojournal ; 19: 23, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35510117

RESUMO

Ever since the introduction of the Papanicolaou (PAP) smear test was published in 1941 in American Journal of Obstetrics and Gynecology, PAP test linked with definitive treatment has prevented millions of women from cervical cancer in the developed countries. Due to limited availability of resources, a lack of infrastructure and difficulty in getting highly trained professionals, widespread implementation of PAP test dependent cervical cancer screening program has not been established in low and middle income countries such as India. Therefore, after availability of non-cytological tests such as visual inspection on acetic acid (VIA) and human papillomavirus (HPV) DNA test, there is a paradigm shift in cervical cancer screening methods. In past two decades, various research work has convincingly established the utility of VIA and HPV test in developing countries. The evidences were evaluated by the World Health Organization (WHO) and recommendations have been recently published for comprehensive cervical cancer control strategies for the low and middle income countries. For any successful screening program, achieving high coverage (>70%) of the target population rather than frequent screening is the most important determinant. It is also equally important to ensure appropriate investigations of the screen positive women to establish the disease and treatment of the screen detected cases of cervical intra epithelial neoplasia (CIN) and cancer. HPV testing is the WHO recommended test for cervical cancer screening especially in view of widespread HPV vaccination in young population leading to lower prevalence of CIN and other HPV related diseases.

7.
Indian J Gynecol Oncol ; 19(3): 41, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34095455

RESUMO

PURPOSE: Cervical cancer is one of the leading cancers among women in India. Its prevention and control require a concerted effort to improve awareness among women regarding primary and secondary prevention strategies as well as access to care for treatment and palliation. A focused strategy is important to reach the World Health Organization's targets for cervical cancer elimination, due to be completed by 2030. METHODS: Currently available literature was reviewed regarding cervical cancer prevention strategies in India including various national programmes and other initiatives on the part of government, non-governmental organizations and professional organizations. Their applicability to the present situation was assessed. RESULTS: National programmes need to build on success stories of various states and neighbouring countries as well as to audit the performance. Strengthening of cancer registries and improvement of linkages between different healthcare levels with incorporation of task-shifting, adding digital technology and supporting programmes that promote women's welfare and health will also provide synergy to cancer control programmes. In the current pandemic era, HPV self-sampling can be an ideal method for screening. The development of an affordable, point-of-care HPV test is urgently needed to facilitate its introduction in low- and middle-income countries. HPV vaccination efforts need to be speeded up. CONCLUSION: Scaling up of cervical cancer prevention with inclusion of widespread HPV vaccination and primary HPV test should be the new standard of care.

8.
Asian Pac J Cancer Prev ; 22(3): 699-704, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33773531

RESUMO

BACKGROUND: Initial introduction of HPV vaccination from 2006 to 2008 was largely confined to high-income countries (HIC), such as Australia, the United States, and Europe, where cervical cancer incidence is lowest. Much of the post-introduction literature has come from HICs, with a focus on coverage levels achieved, provider acceptability and early impact of vaccination on disease endpoints. However, there are a few literature evaluating the mechanics of delivery, feasibility of the health system and acceptability from low and middle income countries (LMICs). The primary objective was to evaluate the feasibility, acceptability and safety of two dose HPV vaccination in adolescent girls between 9-14 years. METHODS: After an orientation camp followed by filling up of prevaccine questionnaires by parents on HPV related diseases and its vaccines and informed consent, girls between9-14years were vaccinated. They were asked to report any side effects in the next 24 hours after each dose. Parents were contacted on Day 7 and Day 30 to enquire about any side effects . Total 3 visits were required i.e two for the vaccination and one visit at 7th month post completion of second dose. To estimate the acceptability, successful completion of two doses by at least 80% of the girls were measured. For measurement of acceptability, either of the parents were recalled along with their daughter at 7th month and were asked to fill up a pre-set questionnaire. RESULTS: After institutional ethical clearance, 555 girls were recruited in the study from rural parts of West Bengal, India between July, 2017 to November, 2017. Out of which, 544 girls (98%) received their 2nd dose between January, 2018 and May, 2018 without any serious adverse effects. No serious adverse effect was reported on follow up till December, 2019. CONCLUSION: The introduction of HPV vaccination is feasible in large scale and the vaccine is well accepted and safe.
.


Assuntos
Programas de Imunização , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/uso terapêutico , Aceitação pelo Paciente de Cuidados de Saúde , Neoplasias do Colo do Útero/prevenção & controle , Adolescente , Criança , Atenção à Saúde , Países em Desenvolvimento , Estudos de Viabilidade , Feminino , Humanos , Índia
9.
Nucleic Acids Res ; 48(21): 12042-12054, 2020 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-32663294

RESUMO

The stability of Watson-Crick paired RNA/DNA hybrids is important for designing optimal oligonucleotides for ASO (Antisense Oligonucleotide) and CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas9 techniques. Previous nearest-neighbour (NN) parameters for predicting hybrid stability in a 1 M NaCl solution, however, may not be applicable for predicting stability at salt concentrations closer to physiological condition (e.g. ∼100 mM Na+ or K+ in the presence or absence of Mg2+). Herein, we report measured thermodynamic parameters of 38 RNA/DNA hybrids at 100 mM NaCl and derive new NN parameters to predict duplex stability. Predicted ΔG°37 and Tm values based on the established NN parameters agreed well with the measured values with 2.9% and 1.1°C deviations, respectively. The new results can also be used to make precise predictions for duplexes formed in 100 mM KCl or 100 mM NaCl in the presence of 1 mM Mg2+, which can mimic an intracellular and extracellular salt condition, respectively. Comparisons of the predicted thermodynamic parameters with published data using ASO and CRISPR-Cas9 may allow designing shorter oligonucleotides for these techniques that will diminish the probability of non-specific binding and also improve the efficiency of target gene regulation.


Assuntos
DNA/química , Oligonucleotídeos Antissenso/química , Cloreto de Potássio/química , RNA/química , Cloreto de Sódio/química , Sequência de Bases , Sistemas CRISPR-Cas , Cátions , DNA/metabolismo , Magnésio/química , Hibridização de Ácido Nucleico , Oligonucleotídeos Antissenso/síntese química , RNA/metabolismo , Análise de Regressão , Sódio/química , Termodinâmica
10.
Int J Gynecol Pathol ; 39(4): 384-390, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32515923

RESUMO

Interpretation of histopathology of cervical premalignant lesions suffers from marked interobserver variability due to its subjective nature. We aimed to evaluate the usefulness of the biomarkers p16 and Ki-67 in improving the diagnostic accuracy of cervical histopathology and assess the correlation between p16 expression and human papillomavirus test in different grades of cervical intraepithelial neoplasia (CIN). Cervical tissue specimens with a diagnosis of CIN 1 or worse (CIN 1+) on hematoxylin and eosin staining were selected for immunohistochemistry (IHC) staining for p16 and Ki-67. The IHC slides were examined by a gynecologic pathologist along with a review of hematoxylin and eosin slides. The review histopathology diagnosis was used to correlate with the IHC results. We observed that the proportion of women with overexpression of p16 increased with increasing histologic severity: 0% in women with normal histology; 33.3% in women with CIN 1; 58.1% in women with CIN 2; and 73.8% in women with CIN 3. Among the human papillomavirus-positive women, 76.3% (58/76) women with CIN 2/CIN 3 expressed p16, and only 8.9% (4/45) women with normal histopathology or CIN 1 expressed the same. A combination of p16 positivity and abnormal expression of Ki-67 beyond the lower third of the epithelium was observed in 0% of normal/CIN 1 and 60.5% (40/66) of CIN 3 detected on routine histopathology. We concluded that dual staining could be used as an adjunctive test to improve the diagnostic accuracy of histopathology. In addition, p16/Ki-67 IHC has a role in guiding management decisions in cases with discordant colposcopy and histopathology diagnoses.


Assuntos
Biomarcadores Tumorais/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Antígeno Ki-67/metabolismo , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Colposcopia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Variações Dependentes do Observador , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Displasia do Colo do Útero/metabolismo , Displasia do Colo do Útero/patologia
11.
Asian Pac J Cancer Prev ; 21(5): 1391-1398, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32458647

RESUMO

BACKGROUND: The prospective randomized study aimed to compare the safety, acceptability and efficacy of thermal ablation (TA) to that of cryotherapy in screen and treat setting. METHODS: The participants were recruited prospectively in a community-based screening clinic in India. Women positive on visual inspection with acetic acid (VIA) test and/or Human Papillomavirus (HPV) test were assessed for eligibility for ablative treatment. Total 286 eligible women were randomized to receive either cryotherapy (N=150) or TA (N=136) performed by health workers. Colposcopy and cervical biopsy were performed on all, prior to treatment. Post-treatment follow-up was after one year with colposcopy and biopsy. RESULTS: Both the treatment methods had high acceptability. Significantly higher proportion of women treated by cryotherapy reported pain compared to women treated by TA, though intensity was mild in vast majority of them. Approximately 30% of women in both arms had histologic abnormalities, mainly CIN 1, and among those who attended follow-up 74.1% and 81.0% didn't have any CIN after cryotherapy and TA respectively. CONCLUSION: TA is as acceptable and safe as cryotherapy in screen and treat setting. TA has the logistic advantages for the low-resourced settings as the machines are more portable, do not require costly refrigerant gas and battery-driven models are available. The cure rates for CIN 1+ lesions in our study were comparable between cryotherapy and TA.


Assuntos
Técnicas de Ablação/métodos , Crioterapia/métodos , Detecção Precoce de Câncer/métodos , Hipertermia Induzida/métodos , Infecções por Papillomavirus/complicações , Displasia do Colo do Útero/terapia , Neoplasias do Colo do Útero/terapia , Adulto , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Segurança do Paciente , Prognóstico , Estudos Prospectivos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologia
12.
Artigo em Inglês | MEDLINE | ID: mdl-32081425

RESUMO

Telomeric G-quadruplex topology has the ability to regulate telomerase activity, which counteracts the shortening of telomere with successive cell divisions, thereby causing genomic longevity. However, the detailed mechanism of G-quadruplexes topologies formed by telomeric sequences requires further investigation. In this study, we quantitatively investigated the effect of cosolutes, particularly the varying number of hydroxyl groups, on the structural transition between hybrid type and parallel G-quadruplexes formed by telomeric DNA sequences. Cosolutes with one or no hydroxyl groups in the vicinal position more efficiently induced the transition to parallel G-quadruplex from hybrid G-quadruplex than those with more hydroxyl groups. We also examined the effect of cosolute structures on the hydration of G-quadruplex formation; the results indicated that cosolutes with fewer hydroxyl groups lead to the release of greater amount of water during G-quadruplex formation. Molecular dynamics results showed that the parallel G-quadruplex was more dehydrated than the hybrid type G-quadruplex. Generally, a dehydrated structure is favored under crowding condition. Thus, depending on the surrounding cosolutes, the G-quadruplex topology can be controlled by the G-quadruplex hydration state.

13.
BMC Womens Health ; 18(1): 89, 2018 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-29890991

RESUMO

BACKGROUND: This cross-sectional pilot study evaluates diagnostic accuracy of live colposcopy versus static image Swede-score evaluation for detecting significant precancerous cervical lesions greater than, or equal to grade 2 severity (CIN2+). METHODS: VIA or HrHPV positive women were examined using a mobile colposcope, in a rural clinic in Kolkata, India. Live versus static Swede-score colposcopy assessments were made independently. All assessments were by gynecologists, junior or expert. Static image assessors were blinded to live scoring, patient information and final histopathology result. Primary outcome was the ability to detect CIN2+ lesions verified by directed biopsies. Diagnostic accuracy was calculated for live versus static Swede-score in detecting CIN2+ lesions, as well as for interclass correlation. RESULTS: 495 images from 94 VIA positive women were evaluated in this study. Thirteen women (13.9%) had CIN2+ on biopsy. No significant difference was found in the detection of CIN2+ lesions between live and static assessors (area under curve = 0.69 versus 0.71, p = 0.63). A Swede-score of 4+, had a sensitivity of 76.9% (95% CI 46.2-95.0%) and 84.6% (95% CI 54.6-98.1%), for live- and static-image assessment respectively. The corresponding positive predictive values were found to be 90.9% (95% CI 75.7-98.1%) and 92.6% (95% CI 75.7-99.1%). The interclass correlation was good (kappa statistic = 0.60) for the senior static assessors. CONCLUSIONS: Swede-score evaluation of static colposcopy images was found to reliably detect CIN2+ lesions in this study. Larger studies are needed to further develop the colposcopy telemedicine concept which may offer reliable guidance in management where direct specialist input is not available. TRIAL REGISTRATION: Ethical approval of the study was obtained by the Chittaranjan National Cancer Institute (CNCI) Human Research Ethics Committee (4.311/27/2014). The trial was retrospectively registered in the Clinical Trails Registry of India CTRI/2018/03/012470 .


Assuntos
Biópsia/métodos , Colposcopia/métodos , Lesões Pré-Cancerosas/diagnóstico , Telemedicina/métodos , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia , Adulto , Estudos Transversais , Técnicas de Diagnóstico Obstétrico e Ginecológico , Feminino , Humanos , Índia , Pessoa de Meia-Idade , Projetos Piloto , Estudos Retrospectivos , Sensibilidade e Especificidade
14.
Phys Chem Chem Phys ; 19(19): 11937-11946, 2017 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-28440391

RESUMO

The detailed photophysics of (E)-1,5-diphenyl-3-styryl-4,5-dihydro-1H-pyrazole (DSDP) and (E)-1,5-diphenyl-3-styryl-1H-pyrazole (DSP) has been investigated and compared to demonstrate the drastic modification of the photophysics upon dehydrogenation of the pyrazoline ring. While DSDP gives dual absorption and dual emission bands corresponding to the locally excited (LE) and the intramolecular charge transfer (ICT) species, DSP yields single absorption and emission bands for the locally excited species only. Comparative steady state and time resolved fluorometric studies reveal that aromatization of the pyrazoline ring inhibits the formation of the ICT species. Quantum chemical calculations corroborate and rationalize the inhibition of the ICT process upon aromatization through depiction of the differential electronic distributions in the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) of the two fluorophores.

15.
Pathol Oncol Res ; 23(4): 845-852, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28101801

RESUMO

Cancer of the uterine cervix (CACX) is one of the most common carcinoma affecting women worldwide. During treatment, histologically lymph node (LN) metastasis and presence of HPV DNA in blood plasma act as a major prognostic factor. Despite the lack of apparent LN involvement, some early-invasive CACX patients have shown recurrences and poor survival. This is suggestive of undetected early dissemination of cancer cells characterized by presence of HPV DNA in histologically non-metastatic LNs which finally progresses into histologically visible metastasis. This present study investigated the status and origin of HPV genome during early dissemination by molecular analysis in primary tumor (PT), histologically non-metastatic pelvic lymph nodes (LNs) and blood plasma (BP) of same patient. First, CACX patients showing signs of early dissemination was identified by detection of HPV in PT (n = 22) and their corresponding histologically non-metastatic pelvic LNs (n = 45) and BP (n = 18) followed by typing of HPV16/18. This was followed by comparative analysis of the physical, copy number and methylation (enhancer/early/late) status of HPV16 genome present in LNs and BP with that of PT. Our study revealed for the first time that the HPV16 genome were frequently present in the integrated form though the copy number was low in both non-metastatic LNs and BP. However, the methylation pattern of PT was discordant with that of corresponding LNs and BP in majority of the cases. Critical assessment of HPV16 profiles established that the presence of hrHPV may be due to the early dissemination of PT cells having significant pathological implications.


Assuntos
Linfonodos/virologia , Metástase Linfática/patologia , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , DNA Viral/análise , Feminino , Papillomavirus Humano 16/genética , Humanos , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética
16.
Int J Cancer ; 140(8): 1850-1859, 2017 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-28108997

RESUMO

Infection with high-risk human papillomavirus (HR-HPV) is transient and clears on its own in majority of the women. Only a few women who have persistent infection may finally develop cervical intraepithelial neoplasia (CIN) or cervical cancer in later years. The risk of progression in the HR-HPV-positive women with normal cervix or low-grade lesion on colposcopy and histopathology at baseline is less studied. We performed a longitudinal study on 650 HR-HPV-positive women with colposcopy and/or histopathology-proved normal or CIN1 diagnosis at baseline to assess the cumulative risk of development of high-grade CIN. After a mean follow-up of 2.1 person years of observation (PYO) (range 0.1-5.1), the cumulative incidence of CIN2+ (6.4%; 3.0/100 PYO) was significantly higher in women who had persistent HR-HPV infection compared to those who cleared the infection (adjusted HR 6.28; 95% CI 2.87-13.73). The risk of viral persistence in women aged 50-60 years was two times higher compared to women aged 40-49 years and three times higher compared to women aged 30-39 years. The probability of having persistent infection increased progressively with higher viral load at baseline (adjusted HR 3.29, 95% CI 2.21-4.90 for RLU ≥100; adjusted HR 2.69, 95% CI 1.71-4.22 for RLU 10-100). Women with increasing viral load at follow-up had four times higher risk of developing CIN2 or worse lesions as compared to those with decreasing load (20.9% vs 4.8%; p < 0.001). In the context of developing countries where cytology or genotyping triaging is not feasible, colposcopy referral of HR-HPV-positive women with advancing age, viral persistence, and increasing viral load may be considered.


Assuntos
Colo do Útero/virologia , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/epidemiologia , Displasia do Colo do Útero/patologia , Adulto , Colo do Útero/patologia , Colposcopia , Feminino , Genótipo , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Gravidez , Fatores de Risco , Esfregaço Vaginal , Carga Viral , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/epidemiologia , Displasia do Colo do Útero/virologia
17.
J Clin Virol ; 87: 43-48, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27992790

RESUMO

BACKGROUND: Human papillomavirus (HPV) is the necessary cause of cervical cancer. Cervico-vaginal infection with pathogens like Chlamydia is a likely cofactor. The interactions between HPV, Trichomonas vaginalis (TV) and Candida spp. are less understood, though inflammation induced by these pathogens has been demonstrated to facilitate oncogenesis. OBJECTIVE: Our study aimed to evaluate the association between Candida spp. and TV co-infection with HPV in cervical oncogenesis. STUDY DESIGN: Women with normal cervix who were high-risk HPV-negative (N=104) and HPV-positive (N=105); women with CIN 1 (N=106) and CIN 2/CIN 3 (N=62) were recruited from a community based cervical cancer screening program. Cervical cancer patients (N=106) were recruited from a tertiary care oncology clinic. High-risk HPV was detected by Hybrid Capture II technique; Candida spp. and TV were detected by culturing the high vaginal swabs followed by microscopic examination in all. The disease status was established by histopathology in all the women. RESULT: HPV-positive women had significantly higher risk of having precursor lesions (of any grade) and cancer compared to HPV-negative women. Candida spp. or TV infection did not alter the risk of low grade or high grade lesions among HPV- positive women. HPV positive women co-infected with TV had higher risk of cervical cancer but not those co-infected with Candida spp. CONCLUSION: The higher risk of cancer observed in the women co-infected with HPV and TV without any enhanced risk of CIN 3 suggests secondary infection of the malignant growth by TV rather than any causal role. Co-infection with Candida spp. and/or TV infection did not increase the carcinogenic effect of HPV on cervix.


Assuntos
Candidíase Vulvovaginal/complicações , Coinfecção/complicações , Infecções por Papillomavirus/complicações , Lesões Pré-Cancerosas/epidemiologia , Tricomoníase/complicações , Neoplasias do Colo do Útero/epidemiologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade
18.
Cancer Causes Control ; 27(10): 1253-9, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27581249

RESUMO

PURPOSE: Many limited-resourced countries have either introduced cervical cancer screening programs or are contemplating to do so using visual inspection after acetic acid application (VIA) or human papillomavirus (HPV) detection tests. Both tests have high false-positivity and a suitable triaging strategy is required. Colposcopy triaging is not practicable in most resource-limited settings due to several reasons. We evaluated a portable, battery-operated, magnifying device (GynocularTM) to triage screen positive women in community setting in India. METHODS: Women positive on VIA or oncogenic HPV test were examined with Gynocular by clinicians in primary health clinics. Findings were documented using the International Federation for Cervical Pathology and Colposcopy (IFCPC) terminology. Swede score was also calculated. Biopsy was performed irrespective of Gynocular findings. The accuracy of Gynocular to detect high-grade lesions or cancer (HSIL+) was estimated. The suitability of Gynocular to correctly triage screen positive cases for immediate ablative treatment was also evaluated by creating simulated scenarios. RESULTS: Sensitivity and specificity of Gynocular were 96.4 and 47.1 %, respectively, to detect HSIL + at the threshold of IFCPC grade 1 findings. Increasing threshold to grade 2 changed sensitivity and specificity to 92.9 and 94.1 %, respectively. Optimum combination of sensitivity and specificity as determined by the receiver operating curve analysis was at the cut-off Swede score of 5. Triaging of VIA/HPV positive women to treatment using grade 2 criteria would have resulted in modest overtreatment and missing of very few high-grade lesions. CONCLUSION: Gynocular can be used as an effective triaging device for VIA/HPV positive women.


Assuntos
Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/virologia , Ácido Acético , Adulto , Biópsia/métodos , Colposcopia , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Índia , Pessoa de Meia-Idade , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Gravidez , População Rural , Triagem , Neoplasias do Colo do Útero/patologia
20.
J Med Screen ; 23(2): 104-10, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26566949

RESUMO

OBJECTIVE: High viral load of oncogenic human papillomavirus (HPV) significantly increases risk of CIN 2 or worse (CIN 2+) lesions. Semi-quantitative estimation of oncogenic HPV viral load by Hybrid Capture 2 (HC2) correlates well with viral load estimated by real-time polymerase chain reaction. We correlated viral load estimated by HC2 with colposcopy and histology diagnosis, to determine if high viral load could detect the CIN 2+ lesions missed by colposcopy in HPV positive women. METHODS: Using HPV testing by HC2, 39,728 women were screened. Positive results were categorized into low-positive, intermediate, and high viral load groups, based on relative light unit/cut-off ratios. HPV-positive and some HPV-negative women underwent colposcopy and biopsy. RESULTS: A total of 278 CIN 2+ lesions were detected. Detection rate of CIN 2+ was significantly higher in intermediate and high viral load groups. Nearly half (48.3%) of CIN 2+ and 80.4% of CIN 3+ lesions missed or under-diagnosed by colposcopy had viral load in intermediate to high ranges. Risk of CIN 2+ in the high viral load group was 46 times higher than HPV-negative women, even when colposcopy was apparently normal. DISCUSSION: Women with intermediate or high viral load should have multiple punch biopsies, even if colposcopy is apparently normal or suggests low grade lesions. Women with high viral load and suspected low grade lesion on colposcopy may be considered for 'see-and-treat', as their risk of CIN 2+ is nearly 200 times higher than HPV-negative women.


Assuntos
Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Colposcopia/métodos , Feminino , França , Humanos , Pessoa de Meia-Idade , Papillomaviridae/genética , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Carga Viral , Serviços de Saúde da Mulher , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologia
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