Showing papers by "Neerja Bhatla published in 2012"

Type-specific incidence and persistence of HPV infection among young women: a prospective study in North India.

Abstract: Background: Infections with human papillomavirus (HPV) are highly prevalent among sexually active young women in India. However, not much is known about the incidence of type-specific human papillomavirus (HPV) infections and their patterns of persistence, especially in the Indian context. Objective: The objective of this study was to evaluate the rate of acquisition and persistence of HPV types in young women. Methods: Women residing in an urban slum in Delhi (n=1300) were followed for 24 months at 6 monthly intervals. Exfoliated cervical cells collected at each visit were tested for the presence of HPV DNA. Genotyping was performed using the reverse line blot assay. Results: The incidence rate for any HPV type was calculated to be 5 per 1000 women-months. Among high risk HPV types, HPV16 had the highest incidence rate followed by HPV59, HPV52 and HPV18, i.e., 3.0, 0.58, 0.41 and 0.35 women per 1000 women-months respectively. The persistence rate was higher for high-risk than low-risk HPV types. Among low-risk types, HPV42, HPV62, HPV84 and HPV89 were found to persist. Whereas almost all high risk types showed persistence, the highest rate was found in women with HPV types 16, 45, 67, 31, 51 and 59. The persistence rate for HPV16 infection was 45 per 1000 women-months. Conclusion: Incident HPV infections and high risk HPV type-specific persistence were found to be high in our study population of young married women. Understanding the patterns of HPV infection may help plan appropriate strategies for prevention programs including vaccination and screening.

Cervical cancer pathogenesis is associated with one-carbon metabolism

Abstract: Cervical cancer is the most common cancer among women in India and a leading cause of death in these women. Most cases of cervical cancer are associated with human papillomavirus (HPV) infection of the high-risk type. It has been reported that aberrant DNA methylation can be associated with HPV infection and cervical cancer, and folate is directly involved in DNA methylation via one-carbon metabolism. We aimed to study the importance of one-carbon metabolism in the progression of cervical carcinogenesis by examining serum levels of vitamin B(12) (cobalamin), homocysteine, and folate and DNA methylation of tumor suppressor genes CDH1, HIC1, and Retinoic acid receptor beta (RARβ) amid these women ranging from normal to squamous intraepithelial neoplastic lesions (SIL) to cervical cancer. Blood and tissue samples were collected from normal (n = 35), SILs (n = 27), and cervical cancer patients (n = 38) in the age group of 26-70 years. Measurement of serum vitamin B(12), folate, and homocysteine were done using kits (Immulite). Promoter methylation was examined using methylation-specific PCR. The frequency of promoter hypermethylation for all the three tumor suppressor genes CDH1, HIC1, and RARβ showed an increasing trend from normal to dysplastic to invasive cervical cancer (p < 0.05). We observed that lower folate and vitamin B(12) status were associated with HPV infection. Taken together, our findings suggest a role of folate and vitamin B(12) in modulating the risk of cervical cancer and HPV infection. CDH1, HIC1, and RARβ genes can be used as potential biomarkers of cervical cancer risk assessment.

Single visit approach for management of cervical intraepithelial neoplasia by visual inspection & loop electrosurgical excision procedure.

Abstract: Background & objectives: Developing a feasible and sustainable model of cervical cancer screening in developing countries continues to be a challenge because of lack of facilities and awareness in the population and poor compliance with screening and treatment. This study was aimed to evaluate a single visit approach (SVA) for the management of cervical intraepithelial neoplasia (CIN) using visual inspection with acetic acid (VIA) and Lugol's iodine (VILI) along with loop electrosurgical excision procedure (LEEP) in women attending Gynaecology OPD in a tertiary care hospital in north India. Methods: In this hospital-based study, 450 women receiving opportunistic screening by conventional Pap cytology were also screened by VIA and VILI. VIA/VILI positive cases underwent same-day colposcopy and biopsy of all lesions. If the modified Reid score was >3, the patient underwent LEEP at the same visit. Results: Of the 450 women screened, 86 (19.1%) and 92 (20.5%) women were VIA and VILI positive, respectively. Detection rates of VIA, VILI and cytology findings at ASCUS threshold were 33.3, 35.5 and 24.4 per 1000, women, respectively to detect a lesion >CIN1. For detection of CIN2+ lesion, detection rates of VIA, VILI and cytology were 20, 22.2 and 22.2 per 1000 women, respectively. Sixteen patients with Reid score >3 underwent the See-and-treat protocol. The overtreatment rate was 12.5 per cent and the efficacy of LEEP was 81.3 per cent. There were no major complications. Interpretation & conclusions: The sensitivity of VIA/VILI was comparable to cytology. A single visit approach using visual screening methods at community level by trained paramedical personnel followed by a combination of ablative and excisional therapy can help to decrease the incidence of cervical neoplasia.

Cervical Cancer Burden and Prevention Strategies: Asia Oceania Perspective

Abstract: The Asia Oceania region contributes to more than 50% of cervical cancer cases worldwide. Yet cervical cancer is one of few cancers that can be prevented through comprehensive screening for precancerous lesions, with their subsequent treatment. Screening with cervical cytology, a very old technology, has reduced cervical cancer mortality and incidence when applied in comprehensive programs with high coverage and high quality assurance. However, of those countries within this region that have set up such programs, many have been opportunistic, had poor coverage, or inadequate treatment facilities for lesions found. Consequently, they have not seen large reductions in cancer incidence or mortality. Some have therefore adopted visual inspection by acetic acid (VIA) and Lugol's iodine (VILI) or human papillomavirus (HPV) DNA assays for screening. With two safe, immunogenic and efficacious prophylactic vaccines licensed, the way forward to reduction of cervical cancer to becoming uncommon is within reach. Where governments have supported high coverage public-health vaccination programs, reductions in disease burden with shortest incubation (genital warts, high-grade abnormalities) are already being reported. One of the biggest impediments is the cost of vaccines that are affordable to resource-poor countries. Other challenges include, infrastructure for delivery of vaccines, plus general acceptance of vaccination by the community.

Human papillomavirus deoxyribonucleic acid testing in developed countries.

Abstract: Cervical cancer has been largely eliminated in developed countries with the implementation of cytology-based screening programmes that depend on a call–recall system, followed by colposcopy and biopsy, treatment of precancerous lesions and follow up. With the discovery that persistent infection with high-risk human papillomavirus types is necessary for the development of cervical cancer, several tests for human papillomavirus deoxyribonucleic acid have been developed that can identify women at risk. Human papillomavirus deoxyribonucleic acid testing is more sensitive and only slightly less specific than cytology for detecting cervical intraepithelial neoplasia. It is also more reproducible, with the potential for self-sampling. Human papillomavirus genotyping, messenger RNA analysis and other biomarkers can help to further stratify this group and diminish referrals to colposcopy. Initially, human papillomavirus testing was used as an adjunct to cytology for triage of borderline cases, but evidence has shown its superiority as a screening method and in the follow up of women treated for cervical intraepithelial neoplasia.

Adjunctive testing for cervical cancer screening in low resource settings.

Abstract: Background Cervical cancer screening using cytology is expensive and requires repeat testing with loss to follow-up for triage. Adjunctive testing using two tests in a parallel or sequential combination can improve diagnostic accuracy, decrease costs and minimise referral rates. Aim To evaluate the performance of visual inspection with acetic acid (VIA), human papillomavirus (HPV) DNA and cervical cytology in sequential and parallel combinations, to determine the optimum screening strategy. Methods A total of 548 symptomatic women presenting to a gynaecology clinic were screened using conventional cytology; HPV testing of self- and physician-collected samples using HC2 assay; and VIA. All women underwent colposcopy with biopsy from all lesions as the reference standard. Test characteristics were calculated individually, and then applied jointly in parallel and sequential combinations. Results Biopsy-proven CIN2+ was present in 40 (7.8%) women. The sensitivity and specificity, respectively, of the various tests were as follows – VIA 82.5, 66.9%, Pap (≥ASCUS) 77.5, 86.8%, HPV-Physician (HPV(P)) 90.0, 91.5%, HPV-Self (HPV(S)) 80.0, 88.1%. Among the adjunctive testing scenarios, sequential testing performed better than parallel. VIA followed by HPV test had the highest specificity (90.4%) and diagnostic accuracy (90.5%), comparable to HPV-P followed by Pap. Conclusions Sequential testing combination of VIA and HPV, followed by colposcopy and directed biopsy for diagnosis, combines economic viability with high scientific fidelity. The high specificity and negative predictive value reduce referral and treatment rates, as well as number of visits required for diagnosis. HPV (P) followed by reflex Pap is a suitable option for high resource situations with access to liquid-based cytology.

A Comparative Study of Apoptosis in Placentas of Normal and Preeclamptic Indian Pregnant Women by TUNEL Assay and M30 Immunostaining

Abstract: Background Preeclampsia is a unique life-threatening disorder of human pregnancy associated with the abnormal placentation caused by the inadequate trophoblastic invasion due to altered apoptosis of these cells. The aim of the present study was to assess and compare the apoptosis in trophoblastic cells in various zones (villous and extravillous) of placentas of preeclamptic and normotensive nonproteinuric pregnant women. Methods Hematoxylin eosin staining, TUNEL assay and M30 immunostaining techniques were used for studying apoptosis in trophoblastic cells of placentas of two groups. The results of apoptotic indices by these techniques were compared in preeclamptic group. Results The TUNEL apoptotic indices were higher in all the zones of placentas of preeclamptic group as compared to control group though the results were not statistically significant. M30 immunostaining also gave higher apoptotic indices in all the zones of preeclamptic placentas as compared to the normal group but the result of apoptotic index of basal plate was not statistically significant. M30 immunostaining was absent in stromal cells. Conclusion In our study, the trophoblastic apoptotic rates were more in villous as well as extravillous zones of preeclamptic placentas as compared to normal placentas and M30 immunostaining was found to be more sensitive and specific for the apoptotic trophoblastic cells as compared to TUNEL assay.

HPV vaccination: more evidence of benefit.

Abstract: 1 Dowdy DW, Steingart KR, Pai M. Serological testing versus other strategies for diagnosis of active tuberculosis in India: A cost-effectiveness analysis. PLoS Med 2011;8:e1001074. 2 World Health Organization. Expert group meeting report on commercial serodiagnostic tests for diagnosis of tuberculosis. Geneva:WHO; 2010. 3 Grenier J, Pinto L, Nair D, Steingart K, Dowdy D, Ramsay A, et al. Widespread use of serological tests for tuberculosis: Data from 22 high-burden countries. Eur Respir J 2012;39:502–5. 4 Steingart KR, Flores LL, Dendukuri N, Schiller I, Laal S, Ramsay A, et al. Commercial serological tests for the diagnosis of active pulmonary and extrapulmonary tuberculosis: An updated systematic review and meta-analysis. PLoS Med 2011;8:e1001062. 5 World Health Organization. Policy statement: Commercial serodiagnostic tests for diagnosis of tuberculosis. Geneva:World Health Organization; 2011.