The baseline survey was conducted between July and December 2011 and was implemented in two areas of Bangladesh; one rural and one urban (Figure 1a). The urban area is located in Dhaka, the capital of Bangladesh, which is the largest metropolitan city in the country. Dhaka city is divided into 92 administrative wards (smallest administrative urban geographic unit), each with an approximate population of 90,000 or more. The International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), an international research organization, has maintained a surveillance site for one of its on-going research projects since 2010 in Ward 2 (Figure 1b) covering a population of approximately 27,000. For the purpose of surveillance, Ward 2 is divided into 9 clusters. For this study, we purposely selected 3 of these 9 clusters. All ever- married women aged 13–64 years and living in these three clusters (n = 4,484) constituted the sampling frame for the urban compo- nent of the study.
As described in Table IV, concurrent STD were significantly related to progressive lesions and even after adjustment it has showed to be significantly associated to progression (Adjusted OR 13.0, P=0.0002). STDs probably contributed to progres- sion of the HPV lesions by depressing local im- munity of the genital tract. Although poorly un- derstood, host cellular defence mechanisms seem to play an important role in controlling HPV in- fection. Patients with cellular immune deficiencies (such as HIV-positive ones) have higher rates of HPV infection and are more susceptible to develop high grade SILs (Ho et al. 1994). In accordance to our findings, Meekin et al. (1992) described a link between previous or current STDs and progression to HPV-induced high grade lesions, proposing that these infections might act as markers for develop- ing SILs. Other studies suggested that other cervi- cal infections may interact with HPV increasing the risk of developing HSILs (Koutsky et al. 1992). The effect of OC use on cervical carcinogenesis has been widely investigated. The incidence of cervical carcinoma was found to be higher amongwomen who had used OC compared to non-users. Stern et al. (1977) have suggested that the progres- sion rate might be higher in OC users than in other women. Nevertheless, we have not found any sig- nificant correlation when statistical significance were analyzed (AOR1.4, P=0.7). These results are in agreement with those from other authors (Davidson et al. 1994).
HumanPapillomavirus (HPV) infection is the most prevalent sexually-transmitted virus worldwide. It is known to be the etiological agent of cervical cancer and cervical intraepithelial neoplasia (CIN). Consequently, there is strong motivation to evaluate HPV testing in cervical cancer screening. Recently developed, the second generation of the hybrid capture test (HCA II) is a non-radioactive, relatively rapid, hybridization assay, designed to detect 18 HPV types divided into high and low-risk groups. We evaluated 7,314 patients (5,833 women and 1,481 men) for HPV infection by HCA II. Among them, 3,008 (41.1%) presented HPV infection: 430 (14.2%) had HPV DNA of low risk for cancer, 1,631 (54.2%) had high risk HPV types and 947 (31.5%) had both types. The prevalence in females was 44.9%. The prevalence of HPV DNA in the group for which cytological results were available was slightly higher: 55.3% (1007/1824). Significant differences were detected in the frequency of HPV infection of the cervix between normal cases and those with high-grade squamous- intraepithelial lesions (HSIL)(P<0.0001). Among males, the prevalence was 26.2%, composed of 9.1% in Group A, 9.7% in Group B and 7.4% with multiple infections. We observed that male prevalence was lower and that low-risk types were more frequent than in females. HPV viral load was significantly greater in SILs than in normal or inflammatory cases (P<0.0001), suggesting an association between high viral load values and risk of SIL. Because of high costs, the HCA II test cannot be recommended for routine mass screening for cervical infectionin poor countries. Nevertheless, it was found to be a useful tool, when combined with cytology, discovering high-risk infections in apparently normal tissues and revealing silent infections that may be responsible for the maintenance of HPV in the general population. These findings point to the need for close and careful management of patients, thereby reducing overtreatment, allowing analysis of both sexual partners and finally contributing to the control of genital infections associated with a risk for cancer.
Diverse rates of concordance in HPV types have been described in various studies on couples, ranging from 60 to 10%: Widdice et al. (17) studied heterosexual couples infected with HPV and detected concordant HPV types in more than 60% of cases, while Castellsague´ et al. (18) found 32% of agreement and suggested that this low rate was due to the different levels of biological activity of the male and female genital tract as well as to differences in local immunity and organization of the genital epithelia of each sex. Physical and immunological protection against pathogenic processes may account for the establishment of different HPV genotypes at specific genital sites. The degree of keratin expression, the number of epithelial layers within each stratum as well as colonization by bacterial flora may determine different patterns of viral infection (19). Rosenblatt et al. (6) found only 13% of agreement, and proposed a complete different panel, whereby reincidence of lesions in CIN women might not be associated with reinfection from sexual partners but rather with a true recurrence of a latent infection. Nevertheless, there is no experimental model of HPV infection insuring the occurrence of true latency, and proposals are mainly theoretical, based on other DNA viruses that infect the genital tract, such as herpes simplex virus. Hence, latency remains a possible outcome of HPV infection but needs to be elucidated. Gravitt (20) has already mentioned that currently there are no tools to conclusively differentiate latency, persistence and transi- tion status of infection and reinfection.
Our analysis revealed that infections caused by high-risk HPV types were predomi- nant (61%). HPV-16 and HPV-6 were the most prevalent among the high- and low-risk types, respectively. On the other hand, HPV-18 and HPV-11 were verified as less prevalent (2%) in the population. The second most common type of high- and low-risk HPV detected were HPV-66 (5%) and HPV-61 (12%), respectively. The most common viruses found inwomen with normal cytology were HPV-16, HPV-18, HPV-31, HPV-58, and HPV-52 (de Sanjosé et al., 2007). Data on the prevalence of HPV reported by IARC revealed that viral prevalence can differ almost 20 times between regions. HPV-16 is the most prevalent type, although large differences can be found in its distribution compared to that of other virus types inwomen with no cytological abnormalities. HPV-18 presents lower prevalence rates in various regions (Clifford et al., 2005). In a Colombian survey, infections with HPV-16 were the most frequent, followed by HPV-58 (Molano et al., 2002). Studies from the Netherlands, Mexico, and Great Britain reported HPV-31 as the second most frequent type. Herrero et al. (2000) described oncogenic types 58, 51, and 52 as relatively abundant in Costa Rica, followed by types 31 and 18. In Japan and Taiwan, HPV-52 was reported as the most prevalent type. HPV-53 has been detected frequently in Brazilian, British, African, and North American women with normal cytology (Jacobs et al., 2000; de Sanjosé et al., 2007).
Study demonstrated that the area wise, urban dwellers had higher knowledge about ‘‘HPV infection causes genital cancer’’ than rural belt and similarly we found that knowledge about ‘‘cervical cancer’’ is higher in urban than rural. This study also showed that more attention is needed to educate the rural populations. In this regard, Li et al reported that (51.1%) urban women knew that HPV is related to cervical cancer in compare to their rural counterpart (41.6%). Even fewer (8.1%) knew that it is associated with genital warts with the similar rate of both geographies . Poor knowledge and awareness of cervical cancer amongwomen and other characteristics has been reported from many different geographic regions [35,53,54,55]. This low level knowledge is consistent with the findingsfrom another study of Chinese womenin Hong Kong, which reported 10% of women were aware of HPV but had limited specific knowledge of HPV . In some other developed countries with well integrated cervical cancer screening program with the Pap test, such as UK and US, the depth of knowledge about HPV were also reported to be very low [56,57,58]. In contrast, a relatively high rate of HPV awareness (51.2%) was reported from a study from Australia, which may be due to the increased media coverage, particularly in relation to the development of an HPV vaccination program . As lack of knowledge is regarded as one of the major barriers that pose challenges to widespread implementation of HPV vaccine in developing countries , increased knowledge of education and health care providers; social workers may help to increase the general knowledge of HPV and HPV related diseases in India.
[22,25,26], is an important determinant of HPV infection, particularly in the GZ region. The more sexual partners that a woman has, the higher risk of getting infected with one or more HPV types over time. There was no significant association with the number of sexual partners in the HK cohort for HPV infection risk, and the result was different from other local studies, where lifetime number of sexual partners was shown to be an independent risk factor [12,27]. This may be attributed to the difference in the study population; their study population included women regardless of their cytological findings, whereas only women with normal cytology were included in our study. Since HPV is mainly sexually transmitted, information on the sexual behaviours of the sexual partners may help to explain the difference findings between the two cohorts. Unfortunately, no such information was available at the present study.
Because of possible concerns with false negative cytology results, all women also undergo a cervicography during one of the visits in their first year of participation in the study—at a time that is mutually convenient for the participant and for the nurses— and then at 24 and 48 months. Cer- vicography is being used to detect clinically relevant lesions that are visu- ally identifiable, thus providing a “safety net” to supplement the infor- mation obtained from the two cytolog- ical readings in the study (see the sec- tion below about management of lesions). Cervicography was proposed as a cervical cancer screening tool by Stafl (5) and plays a useful role in large-scale studies in high-risk popula- tions, particularly in remote areas, where well-trained colposcopists can- not be recruited easily. Log sheets and rolls of film are prepared according to the instructions from the provider, Na- tional Testing Laboratories (NTL), and then shipped monthly to Fenton, Mis- souri, United States of America, for de- velopment and evaluation by NTL’s expert colposcopists. The list of results are then mailed to the project manager in Montreal for computer data entry.
Sixty-two women were enrolled in this study. They were categorized into five groups according to the cytopathological exam: 33 presented no lesions; six presented atypical squamous cells of undetermined significance (ASC-US) (n = 5) or atypical squamous cells that cannot exclude high-grade squamous intraepithelial lesion (ASC-H) (n = 1); seven were classified as LSIL; 13 were HSIL; and three presented tumors (one invasive squamous cell carcinoma, degree I of stage IIB; one undifferentiated carcinoma, degree IV; one microinvasive carcinoma of stage IA1). The mean age of the enrolled women was 41 years-old [standard deviation (SD) ± 12.2] and the first sexual intercourse was on average at 17.3 years of age. The mean number of sexual partners was 5.1. Only 29% of patients used condom during
The infection by human papilloma virus (HPV) is the most common sexually transmitted disease worldwide, with high-risk viral types associated to cervical carcinogenesis. Although there are several virus typing methods, the best test is still under investigation. This study has compared the effectiveness of type-specific PCR and sequencing aiming at their clinical application. Two hundred and sixty cervical samples of HPV-positive patients were studied by type-specific PCR for types 6, 11, 16, 18, 31, 33 and 35 and sequencing. Genotype was identified in 36% of cases by type-specific PCR and in 75% by sequencing. Sequencing was four times more likely to identify the viral type present in positive samples than type-specific PCR (p=0.00). In spite of sequencing being more effective for virus genotyping, this method cannot identify viral types in multiple infections. By combining both methods, we reached a highly sensitive detection (87%), showing that they are complementary methods. Based on these results, in order to genotype clinical samples we propose to start with sequencing and, if necessary, in cases of multiple infections, type-specific PCR should be performed. HPV genotyping plays an important role in guiding the search for specific types to be investigated in routine tests, to allow selecting patients with a higher risk of developing cervical cancer and to contribute to develop type-specific vaccines.
It is also known that the process of oncogenesis is rela- tively slow and develops principally as a biological contin- uum, from the initial intraepithelial neoplasm to the invasive cancer. It usually lasts several years, but there have been some described cases with a 6-month period of genesis. A progres- sive course of the disease is mostly caused by high oncogenic potential viral infection, although it may be significantly af- fected by cocarcinogens, particularly the immune status of a patient. According to different and numerous results of studies, a significant number of HPV infections regresses spontane- ously or persists in a latent stage, while lesser number leads to cervical neoplasms. Already developed cervical intraepithelial neoplasm may also regress spontaneously, but the possibility for this to happen would be lesser if the neoplasm stage was higher. For instance, the cancer in situ will progress into inva- sive cancer in about 70% of cases 14–17 .
There is considerable data to support a central role for humanpapillomavirus (HPV) in the etiology of cervical cancer. More than a 100 HPV types have been described, and 40 have been isolated from benign and malignant genital lesions. Consequently, there is strong motivation to evaluate HPV testing for cervical cancer screening. Few studies concerning the natural history of HPV infection have been conducted in the state of Rio de Janeiro. We determined the prevalence of HPV types in female genital lesions by using Hybrid Capture Assay (HCA) and we retrospectively analyzed the course of HPV infection. Our sample included 788 women attended at Laboratórios Sérgio Franco. The average age of the participants was 29.6 years. HPV prevalence and cytological diagnosis were determined. The overall prevalence of HPV DNA in the study group was 50.1% (395/788), ranging from 25% (NORMAL) to 100% in high-grade intraepithelial lesions (HSIL). High risk HPV was found in 12% inflammatory, 58.3% HPV, 63.2% LSIL and 100% HSIL. A retrospective analysis of 78 patients showed that 22 presented persistent lesions, 2 had progressive lesions, 4 had regressive lesions, 13 showed latent infections, 18 were transiently infected and 19 were submitted to curative treatment. No cases of cancer were registered in this population, which can afford private medical care and regular follow-up exams. We suggest that HCA be used in specific cases involving persistent and recurrent lesions.
The agreement between the molecular methods used in the present study was significant, albeit weak (Kappa = 0.119; p = 0.031). The PCR method was shown to be extremely sensitive, coinciding with data in the litera- ture (Villa & Denny 2006), whereas HC II presented a lower sensitivity, in fact, less than what other authors have reported (Dillner 2001, Castle et al. 2002, Koli- opoulos et al. 2007, De Francesco et al. 2008). In a meta- analysis on tests for identifying HPV, Arbyn et al. (2006) found that the HC II method presented high sensitivity. Some of the findings responsible for the low sensitivity of HC II seen in the present study may be due to the fact that 41 of the 62 HIV-positive patients had HPV types determined using PCR that did not appear in the HC II probes. Among the 21 cases that were positive by PCR and negative by HC II and whose HPV-DNA types were contained in probes A and/or B, the number of copies was lower than the cut-off suggested by the manufac- turer. For probe A, the mean was 0.27, with a standard deviation of 0.14 (minimum 0.10 and maximum 0.89), while for probe B, the mean was 0.35 with a standard deviation of 0.19 (minimum 0.14 and maximum 0.96).
thus represent the HPV prevalence in either single or multiple infections. To express the representation of each type in single and multiple infections, each sample was assigned in proportional fractions to particular genotypes but counted only once . The difference in the HPV prevalence in the group of women with normal cytological findings were compared to those women with atypical findings (ASC-US/AGC-NOS, AGC- NEO/LSIL, ASC-H/HSIL) with 95% confidence intervals (CI) using GraphPad InStat (version 3.00) (GraphPad Software, San Diego, CA). For contingency tables, the standard chi- square test and the Fisher exact test were used. All tests were two sided and the significance level was a=0.05. In order to exclude the differences in age structure between populations we used direct standardization (WHO World standard). The Kappa statistic was used to measure the agreement for HPV positivity status between the two tests used.
One of the most important advances in the control of the spread of infection with type 1 human immunodeficiency virus (HIV- 1) occurred within the context of vertical transmission (VT), with a reduction from levels of more than 40% to levels of less than 3%. Technological progress together with a better physiopathological understanding of this infection has permitted the determination of the situations and factors that increase the rates of perinatal transmission of the virus, indicating which interventions are most adequate for its control. The situations of higher risk for VT of HIV involve maternal, adnexal, obstetrical, fetal, viral, and postnatal factors. Among maternal factors, particularly important is viral load, the major indicator of the risk of this form of transmission. However, despite its relevance, viral load is not the only variable in this equation, with the following factors also playing important roles: use of illicit drugs, multiple sex partners and unprotected sex, malnutrition, smoking habit, advanced maternal disease, and lack af access or compliance with antiretroviral drugs. Among the adnexal factors are prolonged chorion-amniorrhexis, loss of placental integrity, and the expression of secondary receptors in placental tissue. Among the obstetrical factors, it should be remembered that invasive interventions in the fetus or amniotic chamber, internal cardiotocography, type of delivery, and contact of the fetus/newborn infant with maternal blood are also important elements to be controlled. Among the fetal factors are the expression of secondary HIV-1 receptors, genetic susceptibility, reduced cytotoxic T-lymphocyte function, and prematurity. Among the viral factors, mutations and syncytium-inducing strains are believed to be risk factors for VT. Finally, there are postnatal factors represented by an elevated viral load in maternal milk, a low antibody concentration in this fluid, clinical mastitis and nipple lesions, which can be grouped within the context of breast-feeding.
Descriptive analyses were conducted to determine the proportion of recent and long-standing infection by select demographic, behavioral, and biological characteristics. The Kruskal-Wallis test was used to test for differences in medians. Variables associated with recent and long- standing infection at a significance level of p-value <0.2 in bivariate analysis and those known to be risk factors for HIV infection or suspected confounders were included in multinomial logistic regression models which used an ordinal scale of the outcome variable where HIV uninfected was classified as outcome category = 1, serving as the referent group; long-standing infection classified as outcome category = 2; and recent infection classified as outcome cate- gory = 3 . This categorization allowed the model to identify independent and significant risk factors for recent and long-standing infection simultaneously allowing for direct compari- son of the magnitude of the measure of associations reported for recent infection and long- standing infection. A separate multivariate logistic regression model was applied to directly compare recent and longstanding infection with respect to demographic, behavioral, and bio- logical factors. Missing categories were created to account for missing data for female partici- pants for male-specific variables (e.g., male circumcision and presence of male genital sores or ulcers) and male participants for female-specific variables (e.g., current pregnancy based on self-report). Adjusted odds ratios (AOR) and 95% confidence intervals (CI) were presented for the final estimates in the models. Associations with 95% CIs that did not include 1.0 were considered significantly associated with recent or long-standing infection. Data analysis was conducted in SAS version 9.3 (SAS Institute, Cary, NC, USA). All analyses were weighted to account for the complex survey design and adjusted for survey nonresponse.
Statistical analysis - Epidemiological and clinical data were collected in one-on-one interviews in a private room, using a standardised questionnaire. Data were pro- cessed using IBM SPSS Statistics 20. Proportions were compared by Chi-squared testing. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in a uni- variate logistic regression to estimate the relative risk of HPV detection associated with different variables, including age at the time of sampling, gender, skin co- lour, family antecedents, grade of tumour differentiation, and tumour location. Comparisons between viral loads from groups of patients with different histological clas-
We investigated humanpapillomavirus (HPV) infectionin two female populations from diverse socio-economic strata from the state of Rio de Janeiro and we also investigated the possible co-factors related to infection and the progression to cancer. In Group I, the reference group of this study, 10.7% of the patients presented HPV infection, as detected by generic PCR, while in Group II (low socio-demographic conditions) HPV was detected in 31.1% of the samples. HPV16 was the most prevalent virus type found in both Groups I and II (5.3% and 10%, respectively), followed by HPV 18 (1.3% and 4.7%, respectively). Although only a small sample was analysed, we detected differ- ences among the groups regarding the rates of HPV infection, HPV types, age, ethnicity, familial income, schooling, marital status, parity, tobacco smoking and oral contraceptive use. For Group I, the Papanicolaou test was the most powerful independent factor associated with HPV status, followed by an age of under 30 years old, the number of sexual partners and black ethnicity. Our data are in agreement with the co-factors that are typically described for the developed world. For Group II, the Pap test was also the most relevant variable that was analysed, but the his- tory of other sexually transmitted diseases and the use of alcohol were additional factors that were implicated ininfection. These findings point out the need for the development of general and specific strategies for HPV screening of all Brazilian women.
This article reports the HPV status and cervical cytological abnormalities in patients attended at public and private gynecological services from Rio de Janeiro State. It also comments the performance of each HPV DNA tests used. A set of 454 womenfrom private health clinics was tested by routine Capture Hybrid II HPV DNA assay. Among these, 58.4% presented HPV and nearly 90% of them were infected by high risk HPV types. However, this group presented few premalignant cervical lesions and no invasive cervical cancer was registered. We also studied 220 womenfrom low income class attended at public health system. They were HPV tested by polymerase chain reaction using My09/11 primers followed by HPV typing with E6 specific primers. The overall HPV prevalence was 77.3%. They also showed a high percentage of high squamous intraepithelial lesion-HSIL (26.3%), and invasive cervical carcinoma (16.3%). HPV infection was found in 93.1% and 94.4% of them, respectively. The mean ages in both groups were 31.5 and 38 years, respectively. In series 1, HPV prevalence declined with age, data consistent with viral transient infection. In series 2, HPV prevalence did not decline, independent of age interval, supporting not only the idea of viral persistence into this group, but also regional epidemiological variations in the same geographic area. Significant cytological differences were seen between both groups. Normal and benign cases were the most prevalent cytological findingsin series 1 while pre-malignant lesions were the most common diagnosis in the series 2. HPV prevalence in normal cases were statistically higher than those from series 1 (p < 0.001), indicating a higher exposure to HPV infection. Womenfrom both samples were referred for previous abnormal cytology. However, socio-demographic evidence shows that womenfrom series 1 have access to treatment more easily and faster than womenfrom series 2 before the development of pre-malignant lesions. These data provides baseline support for the role of social inequalities linked to high risk HPV infection leading to cervical cancer. Broadly screening programs and the development of safe and effective vaccines against HPV would diminish the toll of this disease that affect mainly poor women.
was the answer of 31.2% respondents followed by cleanliness (27.2%), use of bed nets (26%), isolation of patients (9.2%) and precaution in diet (6.4%). The use of bed nets to control leish- maniasis was the opinion of 9.6% of the subjects, whereas the majority of the respondents (80.8%) were unaware about the preventive measures for leishmaniasis. Regarding the source of information related to sand flies and leishmaniasis relationship, friend, neighbor or teacher was the answer of 40.8% of the subjects followed by television (34.8%), print media (15.2%) and radio (9.2%) (Table 4). Health education interventions in teaching and electronic media can be a successful leishmaniasis information tool . Recently, information related to dengue fever and it vector mosquitoes have been added in the school curricula after severe epidemics of dengue fever in Punjab, Pakistan . Similarly, knowledge of leishmaniasis and its vector may also be included in the curricula as an educational campaign. The addition of such type of knowledge in curricula or health education magazines, particularly in the form of poems, sto- ries, and/or folk songs could be helpful for the well-being of new generations and can put scien- tific learning within its traditional context [19, 20].