Ashrafun Nessa

Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study

BACKGROUND Knowledge about the distribution of human papillomavirus (HPV) genotypes in invasive cervical cancer is crucial to guide the introduction of prophylactic vaccines. We aimed to provide novel and comprehensive data about the worldwide genotype distribution in patients with invasive cervical cancer. METHODS Paraffin-embedded samples of histologically confirmed cases of invasive cervical cancer were collected from 38 countries in Europe, North America, central South America, Africa, Asia, and Oceania. Inclusion criteria were a pathological confirmation of a primary invasive cervical cancer of epithelial origin in the tissue sample selected for analysis of HPV DNA, and information about the year of diagnosis. HPV detection was done by use of PCR with SPF-10 broad-spectrum primers followed by DNA enzyme immunoassay and genotyping with a reverse hybridisation line probe assay. Sequence analysis was done to characterise HPV-positive samples with unknown HPV types. Data analyses included algorithms of multiple infections to estimate type-specific relative contributions. FINDINGS 22,661 paraffin-embedded samples were obtained from 14,249 women. 10,575 cases of invasive cervical cancer were included in the study, and 8977 (85%) of these were positive for HPV DNA. The most common HPV types were 16, 18, 31, 33, 35, 45, 52, and 58 with a combined worldwide relative contribution of 8196 of 8977 (91%, 95% CI 90-92). HPV types 16 and 18 were detected in 6357 of 8977 of cases (71%, 70-72) of invasive cervical cancer. HPV types 16, 18, and 45 were detected in 443 of 470 cases (94%, 92-96) of cervical adenocarcinomas. Unknown HPV types that were identified with sequence analysis were 26, 30, 61, 67, 69, 82, and 91 in 103 (1%) of 8977 cases of invasive cervical cancer. Women with invasive cervical cancers related to HPV types 16, 18, or 45 presented at a younger mean age than did those with other HPV types (50·0 years [49·6-50·4], 48·2 years [47·3-49·2], 46·8 years [46·6-48·1], and 55·5 years [54·9-56·1], respectively). INTERPRETATION To our knowledge, this study is the largest assessment of HPV genotypes to date. HPV types 16, 18, 31, 33, 35, 45, 52, and 58 should be given priority when the cross-protective effects of current vaccines are assessed, and for formulation of recommendations for the use of second-generation polyvalent HPV vaccines. Our results also suggest that type-specific high-risk HPV-DNA-based screening tests and protocols should focus on HPV types 16, 18, and 45.

HPV Involvement in Head and Neck Cancers: Comprehensive Assessment of Biomarkers in 3680 Patients

BACKGROUND We conducted a large international study to estimate fractions of head and neck cancers (HNCs) attributable to human papillomavirus (HPV-AFs) using six HPV-related biomarkers of viral detection, transcription, and cellular transformation. METHODS Formalin-fixed, paraffin-embedded cancer tissues of the oral cavity (OC), pharynx, and larynx were collected from pathology archives in 29 countries. All samples were subject to histopathological evaluation, DNA quality control, and HPV-DNA detection. Samples containing HPV-DNA were further subject to HPV E6*I mRNA detection and to p16(INK4a), pRb, p53, and Cyclin D1 immunohistochemistry. Final estimates of HPV-AFs were based on HPV-DNA, HPV E6*I mRNA, and/or p16(INK4a) results. RESULTS A total of 3680 samples yielded valid results: 1374 pharyngeal, 1264 OC, and 1042 laryngeal cancers. HPV-AF estimates based on positivity for HPV-DNA, and for either HPV E6*I mRNA or p16(INK4a), were 22.4%, 4.4%, and 3.5% for cancers of the oropharynx, OC, and larynx, respectively, and 18.5%, 3.0%, and 1.5% when requiring simultaneous positivity for all three markers. HPV16 was largely the most common type. Estimates of HPV-AF in the oropharynx were highest in South America, Central and Eastern Europe, and Northern Europe, and lowest in Southern Europe. Women showed higher HPV-AFs than men for cancers of the oropharynx in Europe and for the larynx in Central-South America. CONCLUSIONS HPV contribution to HNCs is substantial but highly heterogeneous by cancer site, region, and sex. This study, the largest exploring HPV attribution in HNCs, confirms the important role of HPVs in oropharyngeal cancer and drastically downplays the previously reported involvement of HPVs in the other HNCs.

Visual inspection methods for cervical cancer prevention

The need for simple, cost-effective screening approaches for cervical cancer prevention in low-resource countries has led to the evaluation of visual screening with 3-5% acetic acid. The low reproducibility and wide variation in accuracy reflect the subjective nature of the test. Pooled sensitivity, specificity, positive and negative predictive values were 80%, 92%, 10% and 99%, respectively, for detecting cervical intraepithelial neoplasia grade 2 or worse lesions. Realistic sensitivity of a quality- assured single visual inspection with acetic acid is around 50%. A single round of visual inspection with acetic acid screening has been associated with a 25-35% reduction in cervical cancer incidence and the frequency of cervical intraepithelial neoplasia grade 2 or worse lesions in randomised-controlled trials. Despite all its limitations, implementing visual inspection with acetic acid screening in low-resource countries may provide a pragmatic approach to building up human resources and infrastructure that may facilitate the highly anticipated low-cost, rapid human papilloma virus testing in the near future.

Evaluation of the National Cervical Cancer Screening Programme of Bangladesh and the formulation of quality assurance guidelines

Background/Methodology External quality assurance for the National Cervical Cancer Screening Programme of Bangladesh was done in June 2008 by the United Nations Population Fund (UNFPA). The programme, initiated in 2004, has set up screening facilities in 44 districts of Bangladesh. Women aged over 29 years are screened using visual inspection after acetic acid application (VIA) by trained paramedics. Independent consultants not involved in strategic planning or implementation of the programme were engaged to review the ongoing activities. They visited different service delivery set-ups, collected data using a structured proforma, interviewed the service providers, and held discussions with the programme managers. This paper summarises the observations and recommendations of the experts performing the quality control process. Results/Conclusions The consultants observed that the programme was based on largely opportunistic screening with good central co-ordination and some elements of organised screening. The coverage of the target population at the end of 4 years was very low. The compliance to colposcopy was good, though nearly half of the patients with high-grade precancers did not receive treatment. Cryotherapy was infrequently used and a ‘see and treat‘ policy was rarely followed. No strategy for internal monitoring and quality control was built into the programme. The reviewers enumerated the quality assurance standards at various levels of service delivery based on which the performance assessment can be done periodically. This is the first evaluation report of a VIA-based national cervical screening programme.

Screening for cervical neoplasia in Bangladesh using visual inspection with acetic acid

To report the organization and early results of a visual inspection with acetic acid (VIA) screening program for cervical cancer prevention in Bangladesh.

Comparison between Visual Inspection of Cervix and Cytology Based Screening Procedures in Bangladesh

BACKGROUND Cervical cancer continues to be a major problem in Bangladesh with approximately 18,000 new cases annually of which over 10,000 women die from it. Visual inspection of the cervix after 3-5% acetic acid (VIA) application is a simple and easy to learn method for cervical cancer screening, although cytology-based screening is more often applied in developed countries where it has successfully reduced the prevalence of cervical cancer. OBJECTIVE To compare the efficacy of VIA and cytology-based primary methods for cervical cancer screening in Bangladesh. MATERIALS AND METHODS This hospital based comparative study was conducted at the VIA centre and Colposcopy Clinic of Bangabandhu Sheikh Mujib Medical University (BSMMU) from October 2008 to October 2010. RESULTS Among 650 women, 74 (11.4%) were VIA+ve and 8 (1.2%) had abnormalities in their Pap smear reports. During colposcopy, 38 (7.7%) women had different grades of CIN and 4 (0.6%) had cervical cancer. The gold standard histology findings proved 20 women had CIN I, 14 had CIN II/II and 4 had cervical cancer. Among the 38 histology diagnosed abnormalities, VIA test could identify 30 abnormalities including two cervical cancers. However, Pap smear could detect only 8 cases of histological abnormalities (2 low grade and 6 had high grade lesion) and it missed all the cervical cancer cases. The sensitivity and specificity of VIA were 88.9% and 52.1%. The positive predictive value (PPV) and negative predictive value (NPV) were 41.0%, and 92.6% respectively. Moreover, the sensitivity, specificity, PPV and NPV of Pap smear were 33.3%, 95.8%, 75.0% and 79.3%, respectively. CONCLUSIONS VIA test should be used as the primary screening tool even with its low sensitivity and specificity in low resource countries like Bangladesh. False positive results may be greater, but overtreatment can be minimized by colposcopy evaluation of the VIA positive women.

Evaluation of stationary colposcope and the Gynocular, by the Swede score systematic colposcopic system in VIA positive women: a crossover randomized trial.

Objective This study aimed to evaluate cervical lesions by the Swede coloscopy system, histologic finding, liquid-based cytology, and human papillomavirus (HPV) in women who resulted positive for visual inspection of the cervix with acetic acid (VIA) by using a pocket-sized battery-driven colposcope, the Gynocular (Gynius AB, Sweden). Methods This study was a crossover, randomized clinical trial at the colposcopy clinic of Bangabandhu Sheikh Mujib Medical University in Dhaka, Bangladesh, with 540 VIA-positive women. Swede scores were obtained by the Gynocular and stationary colposcope, as well as samples for liquid-based cytology, HPV, and cervical biopsies. The Swede scores were compared against the histologic diagnosis and used as criterion standard. The percentage agreement and the κ statistic for the Gynocular and standard colposcope were also calculated. Results The Gynocular and stationary colposcope showed high agreement in Swede scores with a κ statistic of 0.998, P value of less than 0.0001, and no difference in detecting cervical lesions in biopsy. Biopsy detected cervical intraepithelial neoplasia (CIN) 2+ (CIN2, CIN3, and invasive cancer) in 38 (7%) of the women, whereas liquid-based cytology detected CIN2+ in 13 (2.5%) of the women. Forty-four (8.6%) women who were tested resulted positive for HPV; 20 (3.9%) women had HPV-16, 2 (0.4%) had HPV-18, and 22 (4.3%) had other high-risk HPV. Conclusions Our study showed that few VIA-positive women had CIN2+ lesions or HPV infection. Colposcopy by Swede score identified significantly more CIN2+ lesions than liquid-based cytology and could offer a more accurate screening and selection for immediate treatment of cervical lesions in low-resource settings.

Screening for and management of high‐grade cervical intraepithelial neoplasia in Bangladesh: A cross‐sectional study comparing two protocols

Aim:  To evaluate the feasibility of the ‘see and treat’ protocol for the management of high‐grade cervical intraepithelial neoplasia (CIN) at a colposcopy clinic in Bangladesh.

Scaling up proven innovative cervical cancer screening strategies: Challenges and opportunities in implementation at the population level in low‐ and lower‐middle‐income countries

The problem of cervical cancer in low‐ and lower‐middle‐income countries (LLMICs) is both urgent and important, and calls for governments to move beyond pilot testing to population‐based screening approaches as quickly as possible. Experiences from Zambia, Bangladesh, Guatemala, Honduras, and Nicaragua, where scale‐up of evidence‐based screening strategies is taking place, may help other countries plan for large‐scale implementation. These countries selected screening modalities recommended by the WHO that are within budgetary constraints, improve access for women, and reduce health system bottlenecks. In addition, some common elements such as political will and government investment have facilitated action in these diverse settings. There are several challenges for continued scale‐up in these countries, including maintaining trained personnel, overcoming limited follow‐up and treatment capacity, and implementing quality assurance measures. Countries considering scale‐up should assess their readiness and conduct careful planning, taking into consideration potential obstacles. International organizations can catalyze action by helping governments overcome initial barriers to scale‐up.

Evaluation of the accuracy in detecting cervical lesions by nurses versus doctors using a stationary colposcope and Gynocular in a low-resource setting

Objectives Evaluation of the performance of VIA (visual inspection with acetic acid) trained nurses to learn colposcopy and the Swede score method to detect cervical lesions by using stationary colposcope or a portable, hand-held colposcope; the Gynocular, as compared to doctors. Design A crossover randomised clinical trial. Setting The Colposcopy Clinic of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. Participants 932 women attending the clinic as either screening naïve for VIA screening (404) or women referred as VIA positive (528) from other VIA screening centres in the Dhaka region. Intervention VIA trained nurses were trained on-site in colposcopy and in the Swede score systematic colposcopy method. The Swede score grade cervical acetowhiteness, margins plus surface. vessel pattern, lesion size and iodine staining. The women were randomised to start the examination by either a stationary colposcope or the Gynocular. Swede scores were first obtained by a nurse and the same patient was equally evaluated by a doctor. Primary and secondary outcome measures Agreement between nurses and doctors in Swede scores was evaluated using the weighted κ statistic for the Gynocular and standard colposcope. The ability to predict CIN 2+ (CIN 2, CIN 3 and invasive cervical cancer) using Swede scores was evaluated using receiver-operating characteristic curves. Results The Swede scores obtained by nurses and doctors using the Gynocular and stationary colposcope showed high agreement with a κ statistic of 0.858 and 0.859, respectively, and no difference in detecting cervical lesions in biopsy. Biopsy detected CIN 2+ in 39 (4.2%) women. Conclusions Our study showed that VIA nurses can perform colposcopy. There was no significant differences compared to doctors in detecting cervical lesions by stationary colposcope or the Gynocular using the Swede score system. Swede scores obtained by nurses using the Gynocular could offer an accurate cervical diagnostic approach in low resource settings. Trial registration number ISRCTN53264564.