Large loop versus straight-wire excision of the transformation zone for treatment of cervical intraepithelial neoplasia: a randomised controlled trial of electrosurgical techniques.

OBJECTIVE: To compare two electrosurgical techniques, straight-wire excision of transformation zone (SWETZ) with large loop excision of transformation zone, as a cone procedure (LLETZ-cone), for the treatment of cervical intraepithelial neoplasia (CIN), when disease is present at the cervical canal. DESIGN: Randomised controlled trial. SETTING: Two public hospitals, one in Rio de Janeiro, Brazil and one in Dublin, Ireland. POPULATION: One hundred and three women with indication to treat CIN located at cervical canal. METHODS: Women were randomised to receive LLETZ-cone or SWETZ. OUTCOMES: Main outcome was the incidence of complete excision of disease at endocervical margin of the surgical specimen. Secondary outcomes were complete excision at ectocervical and stromal margins, time to complete the procedure, specimen fragmentation, blood loss and death after 1 year. RESULTS: Fifty-two women were allocated to LLETZ-cone and 51 to SWETZ. Ten women were lost for main outcome because of damaged specimens. Forty-two women in the LLETZ-cone group had free endocervical margin versus 43 women in the SWETZ group (relative risk 1.04, 95% confidence interval [95% CI] 0.87-1.25; P = 0.64). For secondary outcomes related to margins, we observed a relative risk of 1.15 (95% CI 0.95-1.39; P = 0.15) for ectocervical free margin. For free stromal margin, the relative risk was 1.07 (95% CI 0.89-1.29; P = 0.47). No death was observed. CONCLUSIONS: This study was inconclusive; SWETZ and LLETZ-cone were equally effective to treat endocervical disease, with no difference in protecting against margin involvement. Higher, but not severe, blood loss and longer surgical time were observed in the SWETZ group.

HPV vaccines: a controversial issue?

Controversy still exists over whether the benefits of the available HPV vaccines outweigh the risks and this has suppressed uptake of the HPV vaccines in comparison to other vaccines. Concerns about HPV vaccine safety have led some physicians, healthcare officials and parents to withhold the recommended vaccination from the target population. The most common reason for not administering the prophylactic HPV vaccines are concerns over adverse effects. The aim of this review is the assessment of peer-reviewed scientific data related to measurable outcomes from the use of HPV vaccines throughout the world with focused attention on the potential adverse effects. We found that the majority of studies continue to suggest a positive risk-benefit from vaccination against HPV, with minimal documented adverse effects, which is consistent with other vaccines. However, much of the published scientific data regarding the safety of HPV vaccines appears to originate from within the financially competitive HPV vaccine market. We advocate a more independent monitoring system for vaccine immunogenicity and adverse effects to address potential conflicts of interest with regular systematic literature reviews by qualified individuals to vigilantly assess and communicate adverse effects associated with HPV vaccination. Finally, our evaluation suggests that an expanded use of HPV vaccine into more diverse populations, particularly those living in low-resource settings, would provide numerous health and social benefits.

Efficacy in treatment of subclinical cervical HPV infection without intraepithelial neoplasia: systematic review.

CONTEXT: The treatment of the subclinical Human papillomavirus (HPV) infection of the uterine cervix is controversial. OBJECTIVE: To assess the efficacy of any therapy for subclinical HPV infection of the cervix without intraepithelial neoplasia, via a search in the medical literature. METHOD: We performed a systematic review with a comprehensive reference search in Medline, LILACS, Excerpta Medica, AIDSLINE, Popline, Cochrane Library and other authors' reference lists to identify experimental studies of therapy for subclinical HPV infection without intraepithelial neoplasia of the uterine cervix. In order to identify unpublished studies, we also contacted experts in the area, clinical trial registries, pharmaceutical industries, government and research institutions. We also searched on the Internet and in the book-of-abstracts of some medical conferences. The studies identified were masked and selected by inclusion criteria to help ascertain their internal validity. The data about regression or progression of HPV infection were extracted from the studies included. RESULTS: We identified 67 studies related to the treatment of subclinical HPV infection without intraepithelial neoplasia of the uterine cervix. Only five clinical trials matched the inclusion criteria and none demonstrated significant differences between the experimental group and the control group concerning regression of HPV infection (with or without CIN I) or progression to higher grades of CIN. CONCLUSION: The evidence we found in the medical literature regarding the efficacy of any therapy for subclinical HPV infection without intraepithelial neoplasia of the uterine cervix was unsatisfactory.

Cervical cytological abnormalities and factors associated with high-grade squamous intraepithelial lesions among HIV-infected women from Rio de Janeiro, Brazil.

Although cervical cancer remains a major public health problem in Brazil, knowledge of cervical cytological abnormalities among HIV-infected women remains scarce. At baseline evaluation of a cohort followed in Rio de Janeiro, Brazil, 703 HIV-infected women underwent cytology-based cervical cancer screening and human papillomavirus (HPV) DNA testing. Poisson regression analysis was used to evaluate the association of factors with the presence of high-grade squamous intraepithelial lesions (HSIL). Cervical cytology was abnormal in 24.3% of the women; 4.1% had HSIL. Beyond HPV infection, factors independently associated with the presence of HSIL was age (≥25 and ≤40 years, prevalence ratio [PR] 2.60, 95% confidence interval [CI] 1.11-6.10), and more than three pregnancies was protective (PR 0.33, 95% CI 0.11-0.94). High coverage of cervical cancer screening is warranted to prevent morbidity and mortality from cervical cancer in this population.

HPV vaccines: a controversial issue?

Controversy still exists over whether the benefits of the available HPV vaccines outweigh the risks and this has suppressed uptake of the HPV vaccines in comparison to other vaccines. Concerns about HPV vaccine safety have led some physicians, healthcare officials and parents to withhold the recommended vaccination from the target population. The most common reason for not administering the prophylactic HPV vaccines are concerns over adverse effects. The aim of this review is the assessment of peer-reviewed scientific data related to measurable outcomes from the use of HPV vaccines throughout the world with focused attention on the potential adverse effects. We found that the majority of studies continue to suggest a positive risk-benefit from vaccination against HPV, with minimal documented adverse effects, which is consistent with other vaccines. However, much of the published scientific data regarding the safety of HPV vaccines appears to originate from within the financially competitive HPV vaccine market. We advocate a more independent monitoring system for vaccine immunogenicity and adverse effects to address potential conflicts of interest with regular systematic literature reviews by qualified individuals to vigilantly assess and communicate adverse effects associated with HPV vaccination. Finally, our evaluation suggests that an expanded use of HPV vaccine into more diverse populations, particularly those living in low-resource settings, would provide numerous health and social benefits.

Prognosis of intraepithelial cervical lesion during adolescence in up to two years of follow-up.

Our objective was to describe the evolution of cervical SIL within 24 months of the initial diagnosis, in a cohort study of 147 sexually active adolescents attending a public health service in Rio de Janeiro, between 1993 and 2006. The participants were divided in two groups, according to whether cervical biopsy was performed or not. The median of the interval between sexual debut and the atypical cytopathology was 12 months and in 8.2% of patients there was a diagnosis of HSIL at the first abnormal smear. After a two-year follow-up by cytology, the regression (ASCUS 91%, LSIL 63.6%, HSIL 50%) and progression (LSIL 6.1%) were verified. In the group undergoing biopsy, the final histological regression reached 59.4% for CIN1 and 71.4% for CIN2, while the progression from CIN1 to CIN 2/3 was 3.1%. Our results corroborate the recommendation for conservative management in compliant adolescents due to a high regression rate. However, there should be maintained a careful follow-up based on the possible evolution of the lesion.

Immune factors involved in the cervical immune response in the HIV/HPV co-infection.

AIMS: Immune factors influencing the progression of cervical intraepithelial neoplasia (CIN) to cancer remain poorly defined. This study investigates the expression of RANTES, MIP1alpha, COX1, COX2, STAT3, TGFbetaRI, IL10R, TNFalphaRII and TLR4 in the cervical immune response in HIV/HPV (human papillomavirus) co-infected women. METHODS: Cervical biopsies of 36 patients were assayed by immunohistochemistry, and the Ventana Benchmark System was used for HIV-nef detection. RESULTS: Cervices from HIV-positive patients exhibited nef in cells mainly around blood vessels, and showed a decreased expression of all the immune factors tested except IL10R and STAT3, while RANTES (5.54 cells/mm(2)) was highly expressed in comparison with controls (1.41 cells/mm(2), p = 0.028). COX1 was decreased in the HIV/HPV- (0.32 cells/mm(2), p = 0.017) and HPV-infected patients (0.21 cells/mm(2), p = 0.015) compared with controls (3.28 cells/mm(2)). CONCLUSIONS: It is suggested that RANTES in HIV/HPV co-infection may influence the development of CIN leading to progression to cervical cancer.

In situ detection of SOCS and cytokine expression in the uterine cervix from HIV/HPV coinfected women.

The purpose of this study was to look for associations between a newly described class of suppressors of cytokine signaling (SSI/SOCS) and cytokine expression in the uterine cervix from HIV/HPV coinfected women. We examined the pro-inflammatory cytokines TNF-alpha and IL-6 since their expressions are linked and responsible for many aspects of both localized and systemic inflammatory responses. Further, expression of SSI/SOCS has been implicated in the negative feedback regulation of cytokine receptor signaling. PCR-amplified HIV-1 cDNA was noted mainly in the stroma, showing a perivascular distribution, and most of the infected cells colabeled with the macrophage marker CD68. The distribution of IL-6 and TNF-alpha was in the same area to HIV-1 and much greater than normal cervices from women with no evidence of viral infection. SOCS/SSI-1 and -3 mRNA positive cells in the uterine cervix were commonly detected in these noninfected cervical tissues; however, very few cells that contained SOCS were evident in areas where HIV-1, TNF-alpha, and IL-6 expressing cells were found. This suggests that viral-related suppression of SOCS/SSI-1-3 expression may be a factor in the marked local enhancement of TNF-alpha and IL-6 production which, in turn, may help facilitate viral spread; however, further studies should be done in order to elucidate the exact mechanisms of SOCS in the cervix.

[Underreporting of maternal mortality in Rio de Janeiro, Brazil: comparison of 2 information systems]. / Sub-registro da mortalidade materna no Rio de Janeiro, Brasil: comparação de dois sistemas de informação.

Two notification systems were compared to estimate maternal death underreporting for 1988 in eight public maternity clinics of Rio de Janeiro. The death rates obtained were compared with the corrected maternal death rate (13.9 per 10,000 live births), which represented all deaths validated by either system. The system based on hospital discharge records yielded a maternal death-rate of 11.6 per 10,000 live births, or 16% underreporting when compared with the corrected death rate. Error was due to system failure in processing the discharge forms, and also to the transfer of patients to nonmonitored hospitals. The system based on death certificates, including "presumed" maternal deaths, presented a rate of 6.6 per 10,000 live births, with 52% underreporting in relation to the corrected rate. The official death rate, based on maternal deaths as declared in death certificates, underreported by 60% compared to the corrected death rate. When the two systems were compared with each other, the one based on death certificates showed 62% underreporting in relation to that based on hospital discharge forms. In order to minimize underreporting of maternal deaths and to broaden the knowledge on circumstances relating to those deaths, it is suggested (a) that a perinatal information system be introduced in all obstetric service units, and (b) to monitor the final outcome of patients transferred to tertiary units.