Chapter 8 HPV vaccines

Vaccines to prevent infection with high-risk human papillomaviruses (HPV) will help protect women against cervical cancer, and some are likely to be available within the next year. One vaccine, a quadrivalent vaccine against HPV types 6, 11, 16 and 18 and known as Garadsil ©(Merck &Co., Inc), was approved by the Federal Drug Administration (FDA) for the prevention of cervical cancer, cervical cancer precursors and vulval and vaginal cancer precursors associated with HPV 16 and 18 in June 2006. In addition, the vaccine has been approved for the prevention of genital warts and low grade cervical lesions e.g. cervical intraepithelial neoplasia1. The main vaccines components are recombinant viral capsid proteins assembled into virus-like particles and alum-based adjuvants. If given before HPV infection, the vaccines, which induce HPV type-specific, virus-neutralizing antibodies, have proven safe and highly effective at preventing HPV infection and its clinical consequences, including high-grade cervical lesions. Their use should not immediately alter existing screening programs for cervical cancer, however. Because they incorporate only the 2 HPV types most commonly associated with cervical cancer (HPV-16 and HPV-18), they can only prevent about 70% of cervical cancers. Vaccines to treat existing HPV infection are under development but are unlikely to become clinically available in the near future.

Gravidez na adolescência: estudo descritivo de variáveis psicológicas, sócio-demográficas e das relações objetais em adolescentes gestantes e sexualmente ativas

O presente estudo consta de uma etapa quantitativa e outra qualitativa; tem como objetivos descrever variáveis sócio-demográficas e psicológicas de adolescentes sexualmente ativas e primigestas de um Programa de Assistência Médica e Psicossocial à Adolescência (PAMPA) no período de 2000-2002. Descrever o conteúdo intrapsíquico de fantasias inconscientes em adolescentes. Identificar e correlacionar o conteúdo de fantasias inconscientes de adolescentes sexualmente ativas e primigestas em diferentes situações conjugais. Foram utilizadas as instalações do PAMPA na aplicação de uma entrevista semidiretiva e o Teste de Relações Objetais de Phillipson. Na análise sócio-demográfica verifico-se uma distribuição das adolescentes nas faixas etárias de 16 a 17 anos (31,1%), 14 a 15 anos (23,8%) e, 12 a 13 anos. 93,3%, das adolescentes são solteiras e, 6,7% é casada ou encontra-se em união consensual. Um terço das adolescentes encontra-se abaixo da escolaridade esperada para a faixa etária. A renda per capita de 48,6%, varia entre 0,5 e 1 salário mínimo. 40,2% das adolescentes tiveram a sexarca e destas 10,6% pertencem à faixa etária de 12 a 13 anos; e 48,5% de 16 a 17 anos. Metade das adolescentes sexualmente ativas estão grávidas. 57,6% das gestantes têm de 16 a 17 anos. Das adolescentes que iniciaram a vida sexual na faixa etária de 12 a 13 anos, 52,6% está grávida. 51% das adolescentes que tiveram a sexarca na faixa etária de 14 a 15 anos estão gestando e representam 45,5% do total de gestantes. Quanto à situação conjugal das primigestas, 54,5% é solteira e possui parceiro; já 30,3% encontra-se em união consensual ou é casada como conseqüência da gravidez. Não existem diferenças significativas da renda per capita das gestantes em relação à amostra em geral. 60,6% das gestantes buscaram assistência pré-natal a partir do segundo trimestre gestacional. 62,5% das adolescentes realizaram parto vaginal, 21,9% um parto por fórceps e 15,6% parto por cesariana. Observamos semelhanças no funcionamento psíquico em relação ao Sistema Tensional Inconsciente Dominante entre gestantes e adolescentes sexualmente ativas. Fatores como o não planejamento da gravidez e união conjugal em função da gravidez, são mais significativos, mostrando que o relacionamento conjugal e a maternidade não foram ainda elaborados e intensificam o processo de luto próprio da adolescência. No funcionamento psíquico, das gestantes, existem dificuldades em organizar a identidade sexual, negando modificações próprias da adolescência na tentativa de preservar relações vinculares infantilizadas. O conflito edípico permeia como principal nas relações triangulares, devido ao predomínio de objetos parciais persecutórios, incapacidade de conter o par combinado envolvendo sempre um terceiro excluído. Existe também a necessidade de manutenção de relações fusionais com exclusividade do vínculo não erotizado que levam a angústias intensas nas fantasias de separação, abandono e perda, sentimentos de fragmentação e medo de ataques destrutivo-vingativos. Quanto à período gravídico, as gestantes demonstram ambivalência na aceitação e necessidade de consentimento das figuras parentais, vinculadas à angústia surgida pelo medo de rejeição e abandono

Postcesarean pelvic floor dysfunction contributes to undisclosed psychosocial morbidity

OBJECTIVE: To estimate the prevalence and severity of postcesarean pelvic dysfunction. STUDY DESIGN: Using biopsychosocial interviewing at home, 184 postcesarean primiparas were compared to 100 vaginally delivered women regarding symptoms of stress incontinence, anal incontinence and dyspareunia. Delivery details were confirmed from medical records. RESULTS: Comparison of postcesarean vs. vaginally delivered women revealed stress incontinence in 33% vs. 54% and dyspareunia in 27% vs. 46%, both differences reaching statistical significance, unlike anal incontinence, which was manifest in 51% vs. 44%. When compared to emergency cesarean the relative risk of stress incontinence following an elective cesarean was 0.99 (0.71, 1.39), of dyspareunia 1.02 and of anal incontinence 1.05, indicating no statistically significant difference. Thirty (22%) stress incontinent and 4 (3%) fecally incontinent mothers used pads continuously, suggesting severe physical morbidity. Severe dysphoria (depression) was expressed by 41 (35%) stress incontinent mothers, 38 (30%) with dyspareunia and 34 (26%) with anal incontinence; the association of severe dysphoria with dyspareunia was statistically significant (OR = 2.504 [1.362, 4.602]). Few women came forward to seek help. CONCLUSION: Pelvic dysfunction was similar after elective or emergency cesarean. Compared to vaginal delivery, postcesarean stress incontinence and dyspareunia were less frequent but biopsychosocial morbidity could be severe.

Influence of microbial antigen formulation and delivery route on the immune response

Recent technological advances have resulted in the production of safe subunit and synthetic small peptide vaccines. Unfortunately, these vaccines are weakly or non-immunogenic in the absence of an immunological adjuvant (agents that can induce strong immunity to antigens). In addition, in order to prevent and/or control infection at the mucosal surface, stimulation of the mucosal immune system is essential. This may be achieved via the common mucosal immune system by exposure to antigen at a mucosal surface remote from the area of infection. Initial studies investigated the potential of multiple emulsions in effecting oral absorption and the subsequent immune responses to a lipopolysaccharide vaccine (LPS) after immunisation. Nasal delivery of LPS was carried out in parallel work using either aqueous solution or gel formulations. Tetanus toxoid vaccine in simple solution was delivered to guinea pigs as free antigen or entrapped in DSPC liposomes. In addition, adsorbed tetanus toxoid vaccine was delivered nasally free or in an aerosil gel formulation. This work was extended to investigate guinea pigs immunised by various mucosal routes with a herpes simplex virus subunit vaccine prepared from virus infected cells and delivered in gels, multiple emulsions and liposomes. Comparable serum antibody responses resulted but failed to produce enhanced protection against vaginal challenge when compared to subcutaneous immunisation with alhydrogel adjuvanted vaccine. Thus, immunisation of the mucosal surface by these methods may have been inadequate. These studies were extended in an attempt to protect against HSV genital challenge by construction of an attenuated Salmonella typhimurium HWSH aroA mutant expressing a cloned glycoprotein D-l gene fused to the Es-cherichia coli lac z promoter. Preliminary work on the colonisation of guinea pigs with S. typhimurium HWSH aroA mutants were carried out, with the aim of using the guinea pig HSV vaginal model to investigate protection.

Rapid testing for group B streptococcus during labour: a test accuracy study with evaluation of acceptability and cost-effectiveness

OBJECTIVE: To determine the accuracy, acceptability and cost-effectiveness of polymerase chain reaction (PCR) and optical immunoassay (OIA) rapid tests for maternal group B streptococcal (GBS) colonisation at labour. DESIGN: A test accuracy study was used to determine the accuracy of rapid tests for GBS colonisation of women in labour. Acceptability of testing to participants was evaluated through a questionnaire administered after delivery, and acceptability to staff through focus groups. A decision-analytic model was constructed to assess the cost-effectiveness of various screening strategies. SETTING: Two large obstetric units in the UK. PARTICIPANTS: Women booked for delivery at the participating units other than those electing for a Caesarean delivery. INTERVENTIONS: Vaginal and rectal swabs were obtained at the onset of labour and the results of vaginal and rectal PCR and OIA (index) tests were compared with the reference standard of enriched culture of combined vaginal and rectal swabs. MAIN OUTCOME MEASURES: The accuracy of the index tests, the relative accuracies of tests on vaginal and rectal swabs and whether test accuracy varied according to the presence or absence of maternal risk factors. RESULTS: PCR was significantly more accurate than OIA for the detection of maternal GBS colonisation. Combined vaginal or rectal swab index tests were more sensitive than either test considered individually [combined swab sensitivity for PCR 84% (95% CI 79-88%); vaginal swab 58% (52-64%); rectal swab 71% (66-76%)]. The highest sensitivity for PCR came at the cost of lower specificity [combined specificity 87% (95% CI 85-89%); vaginal swab 92% (90-94%); rectal swab 92% (90-93%)]. The sensitivity and specificity of rapid tests varied according to the presence or absence of maternal risk factors, but not consistently. PCR results were determinants of neonatal GBS colonisation, but maternal risk factors were not. Overall levels of acceptability for rapid testing amongst participants were high. Vaginal swabs were more acceptable than rectal swabs. South Asian women were least likely to have participated in the study and were less happy with the sampling procedure and with the prospect of rapid testing as part of routine care. Midwives were generally positive towards rapid testing but had concerns that it might lead to overtreatment and unnecessary interference in births. Modelling analysis revealed that the most cost-effective strategy was to provide routine intravenous antibiotic prophylaxis (IAP) to all women without screening. Removing this strategy, which is unlikely to be acceptable to most women and midwives, resulted in screening, based on a culture test at 35-37 weeks' gestation, with the provision of antibiotics to all women who screened positive being most cost-effective, assuming that all women in premature labour would receive IAP. The results were sensitive to very small increases in costs and changes in other assumptions. Screening using a rapid test was not cost-effective based on its current sensitivity, specificity and cost. CONCLUSIONS: Neither rapid test was sufficiently accurate to recommend it for routine use in clinical practice. IAP directed by screening with enriched culture at 35-37 weeks' gestation is likely to be the most acceptable cost-effective strategy, although it is premature to suggest the implementation of this strategy at present.

Intrapartum tests for group B streptococcus:accuracy and acceptability of screening

Objective: To assess the accuracy and acceptability of polymerase chain reaction (PCR) and optical immunoassay (OIA) tests for the detection of maternal group B streptococcus (GBS) colonisation during labour, comparing their performance with the current UK policy of risk factor-based screening. Design Diagnostic test accuracy study. Setting and population Fourteen hundred women in labour at two large UK maternity units provided vaginal and rectal swabs for testing. Methods The PCR and OIA index tests were compared with the reference standard of selective enriched culture, assessed blind to index tests. Factors influencing neonatal GBS colonisation were assessed using multiple logistic regression, adjusting for antibiotic use. The acceptability of testing to participants was evaluated through a structured questionnaire administered after delivery. Main outcome measures The sensitivity and specificity of PCR, OIA and risk factor-based screening. Results Maternal GBS colonisation was 21% (19-24%) by combined vaginal and rectal swab enriched culture. PCR test of either vaginal or rectal swabs was more sensitive (84% [79-88%] versus 72% [65-77%]) and specific (87% [85-89%] versus 57% [53-60%]) than OIA (P <0.001), and far more sensitive (84 versus 30% [25-35%]) and specific (87 versus 80% [77-82%]) than risk factor-based screening (P <0.001). Maternal antibiotics (odds ratio, 0.22 [0.07-0.62]; P = 0.004) and a positive PCR test (odds ratio, 29.4 [15.8-54.8]; P <0.001) were strongly related to neonatal GBS colonisation, whereas risk factors were not (odds ratio, 1.44 [0.80-2.62]; P = 0.2). Conclusion Intrapartum PCR screening is a more accurate predictor of maternal and neonatal GBS colonisation than is OIA or risk factor-based screening, and is acceptable to women. © RCOG 2010 BJOG An International Journal of Obstetrics and Gynaecology.

Cervicovaginal vascular endothelial growth factor (VEGF) and risk of preterm birth (PTB)

Objective - During pregnancy, the human cervix undergoes angiogenic transformations. VEGF is expressed in cervical stroma and is proposed to play key roles in the process of cervical ripening and dilation. This study was conducted to evaluate whether cervical secretion of VEGF can be of clinical value in predicting impending PTB. Study Design - In an observational prospective cohort study, we analyzed cervical fluid samples from 103 pregnant women (GA: median [IQR]: 28 [25-31] wks) who presented for either a routine prenatal visit (n=61) or for evaluation of threatened preterm labor (n=42). Cervical secretions were collected under a standard protocol which was followed in all cases. Cervical length (CL) was assessed by transvaginal ultrasound using well-established criteria. Dilation was evaluated by digital exam performed only after collection of the biological samples. VEGF levels were immunoassayed by investigators unaware of the clinical outcome. Main exclusion criteria were ruptured membranes, active labor, vaginal bleeding, vaginal exam or intercourse within 24h. Results were analyzed with and without normalization for total protein. Results - 1) Clinical characteristics of the cohort are presented in Table;2) VEGF was detectable in all specimens, with no correlation between its levels, CL, twins or GA at collection; 3) There was an inverse correlation between VEGF and cervical dilation (R=-0.646, P=0.003); 4) Women with cervical dilation =1 cm had lower VEGF compared to those with a closed cervix (P=0.003); 5) Women who experienced PTB within 14 days (n=11) had lower VEGF (P=0.003); 6) A free VEGF level of =600 pg/mL had a sensitivity, specificity, +LR and -LR of 70%, 95%, 13.5 and 0.3, respectively in predicting PTB within 14 days. Conclusions - Low VEGF levels in the cervicovaginal secretions of pregnant women are associated with an increased risk of PTB within 2 weeks of collection. Active engagement of VEGF in the process of cervical ripening and dilatation and/or increased affinity of extracellular matrix components for VEGF may provide explanation for our findings.

Progesterone release from a silicone intravaginal ring in pigtailed macaques

Background: Heterosexual HIV transmission continues to spread worldwide. Intravaginal rings (IVRs) formulated with antiretroviral drugs hold great promise for HIV prevention in women. IVRs provide the benefit of being coitally-independent and coitally-covert for an extended period. As a proof-of-concept, we tested the in vivo release of progesterone from a silicone elastomer vaginal ring device. Methods: Six female pig-tailed macaques were treated with a GnRH agonist (Lupron) prior to ring placement. Four macaques received a progesterone-loaded silicone ring, and two macaques received a blank silicone ring. Blood, vaginal swabs, CVL, and/or biopsies were collected during ring placement, and after ring removal. Results: The median plasma progesterone levels for macaques with a progesterone IVR were 13,973 pg/ml (day 3), 12,342 pg/ml (day 7), 10,112 pg/ml (day 14), 8445 pg/ml (day 21) and 8061 pg/ml (day 28), with a significant decrease from day 14 to day 21 (P = 0.0286). The median plasma progesterone levels for macaques with a blank IVR were 221±±± ±±88 pg/ml. Macaques with a progesterone IVR had CVL progesterone levels of 20,935 pg/ml (day 7), 6892 pg/ml (day 21) and 11,515 pg/ml (day 28). Macaques with a blank IVR had CVL progesterone levels of 29 �± 13 pg/ml. There were no disturbances to the normal vaginal microflora, and plasma and CVL cytokine analysis did not indicate a proinflammatory response due to ring placement. The vaginal biopsies did not display any pathology following ring removal. Overall, the IVRs were well tolerated without any indication of inflammation or significant changes in the vaginal compartment.

Perceptions of self-testing for chlamydia:understanding and predicting self-test use

Background: Self-testing technology allows people to test themselves for chlamydia without professional support. This may result in reassurance and wider access to chlamydia testing, but anxiety could occur on receipt of positive results. This study aimed to identify factors important in understanding self-testing for chlamydia outside formal screening contexts, to explore the potential impacts of self-testing on individuals, and to identify theoretical constructs to form a Framework for future research and intervention development. Methods: Eighteen university students participated in semi-structured interviews; eleven had self-tested for chlamydia. Data were analysed thematically using a Framework approach. Results: Perceived benefits of self-testing included its being convenient, anonymous and not requiring physical examination. There was concern about test accuracy and some participants lacked confidence in using vulvo-vaginal swabs. While some participants expressed concern about the absence of professional support, all said they would seek help on receiving a positive result. Factors identified in Protection Motivation Theory and the Theory of Planned Behaviour, such as response efficacy and self-efficacy, were found to be highly salient to participants in thinking about self-testing. Conclusions: These exploratory findings suggest that self-testing independently of formal health care systems may no more negatively impact people than being tested by health care professionals. Participants’ perceptions about self-testing behaviour were consistent with psychological theories. Findings suggest that interventions which increase confidence in using self-tests and that provide reassurance of test accuracy may increase self-test intentions.

Knowledge and perceptions about HIV/AIDS and safer sex practices among Korean-Americans in Dade County, Florida

This study was conducted to identify Korean-Americans' knowledge, perceptions, and efficacy (both self and response) relating to HIV/AIDS, as well as safer sex practices. Age, gender, education, Confucianism, religion, and acculturation were also examined for potential relationships with the main variables. A total of 200 Korean-Americans in Dade County, Florida, participated in the study. The mean age of the participants was 32.6 years (range 19-55). The AIDS Risk Assessment Questionnaire (ARA-Q) derived from the AIDS Risk Measurement Study Questionnaire (ARMS-Q) and the Risk Behavior Assessment (RBA) were used for data collection. The overall mean score of HIV/AIDS knowledge was 12.3 (77%) out of a possible 16. Knowledge, and perceptions about HIV/AIDS were not related to safer sex practices. Significant correlations between attitudes toward condoms and the frequency of condom use during oral intercourse were evident. Male subjects reported more sexual partners in their lifetime and more frequent condom use during vaginal intercourse during the last year than female subjects. The number of sexual partners in the last year was not related to perceived HIV/AIDS susceptibility and response-efficacy among men or women, but response-efficacy positively correlated to frequency of condom use among both genders. Acculturation scores were positively correlated with the number of sexual partners and the frequency of condom use during vaginal intercourse for men and women. Further research is needed to determine factors that may increase the cultural relevance of AIDS prevention strategies to the Korean-American community. The findings of this study may be used as a basis for designing culturally-sensitive HIV/AIDS education programs to reach various segments of this ethnic community. ^

Substance use and sexual risk behaviors among adolescent detainees

There is a commonly presumed link among sexual risk behavior, substance use, and other psychosocial factors among adolescents. However, these relationships have been relatively understudied in detained, low-income, minority, substance abusing adolescents. This study addresses this gap in the literature with a secondary data analysis based on a sample of adolescent offenders in two detention and treatment centers in Miami-Dade County. Univariate, bivariate statistical analysis and multivariate logistic regressions were conducted on baseline data from structured interviews with 455 adolescents participating in an NIH funded prevention intervention. Data were analyzed to assess relationships among self-reported substance use, STD history, HIV/AIDS knowledge, condom use, condom use attitudes, and skills, peer and parental approval to use condoms, and race/ethnicity. The adolescent sample was 74.1% male, and 25.9% female and 35.4% African American, 25.1% non-African American Latino, 11.2% White, and 28.4% of other race/ethnicity categories. The mean age was 15.6 years. Results suggested that alcohol use (p < 0.001) and use of marijuana, cocaine and other drugs (p < 0.001) are significant variables when explaining the variability in sexual risk behaviors. Results also suggested that unprotected vaginal, anal, and oral sex increased with higher alcohol and drug use (p < 0.001) and that positive attitudes about personally using condoms (p < 0.001) were also significantly related to condom use. Logistic regressions showed that race/ethnicity was a significant control variable when explaining the variability of condom use. Being White and Latino were significantly associated with less condom use during oral and anal sex when compared to other racial/ethnic groups. These results indicated that risky sexual behavior and HIV infection risk are significantly associated with substance use, particularly alcohol use. Therefore, proper screening and identification of alcohol use, and condom use attitudes could maximize the efficacy of referrals to programs targeting both issues and increase the potential for appropriate primary and secondary prevention and treatment among adolescent detainees.

The effectiveness of an enhanced cognitive behavioral intervention in improving behavioral outcomes related to HIV prevention

This study analyzed outcomes of an enhanced cognitive-behavioral intervention with dually diagnosed severely mentally ill adults. It specifically addressed the improvement of attitudes, skills, self-efficacy to use condoms and the heightening of condom use. The data were analyzed via a randomized three-group repeated measures design composed of the experimental (E-CB), standard care (SC) comparison or a no-treatment control condition as the between-subjects variable and pre-post measure as the within-subjects variable. The E-CB focused on cooperative, application, hands-on, skill-building and role-playing activities for sexual assertiveness, negotiation in risk-taking and proper condom use. The SC comparison, was didactic in its approach and addressed risk-taking and proper condom use in one session, but did not involve application approaches to problem-solving risky situations or condom use. Multiple assessments were conducted at pre-, post- and six months post-intervention. ^ The analysis indicated that the E-CB intervention led to more favorable attitudes toward condoms and to improved and maintained skills regarding their use by participants six months after the intervention compared to the standard care and control groups. No significant improvements in self-efficacy were found. A repeated measures ANOVA conducted on the transformed values of percentage of vaginal condom use indicated no significant differences between the experimental and standard care conditions but both had a significantly higher mean percentage vaginal condom use than the control group, averaged across pre- and six-month post-intervention. No gender differences were seen in attitudes, skills or self-efficacy to use condoms. ^ This study shed light upon the effectiveness of the instructional approach for the enhancement of attitudes, skills and self-efficacy outcomes related to HIV prevention. For heightened effectiveness, future approaches must address multiple factors impacting learning in this population. ^

Stress Urinary Incontinence in Female Athletes

Objective: The purpose of this study is to educate allied health professionals and female athletes of the anatomy of the pelvic floor, and the pathology, etiology, and prevalence of stress urinary incontinence in female athletes. Background: Urinary incontinence is not a life-threatening or dangerous condition, but it is socially embarrassing, may cause the individual to remove herself from social situations, and decrease quality of life. While typically associated with parous women who had vaginal delivery, research has shown prevalence of the condition in physically active women of all ages. Stress urinary incontinence has shown to lead to withdrawal from participation in high-impact activities such as gymnastics, aerobics, and running. It may be considered a barrier for life-long athletics participation in women. Description: An in-depth introduction to the cause and origin of stress urinary incontinence including review of the female pelvic floor anatomy and prevalence of stress urinary incontinence in the female athletic population. Clinical Advantages: Athletic trainers and other allied health professionals will develop an understanding of the multiple mechanisms that cause stress urinary incontinence. Clinician competency of the dynamics and mechanism of urinary incontinence prepares the individual to learn diagnostics, prevention, pharmacological intervention, and treatment of this pathology.

Epidemiologic Features of Vulvovaginal Candidiasis among Reproductive-Age Women in India

Background. Vulvovaginal candidiasis is characterized by curd-like vaginal discharge and itching, and is associated with considerable health and economic costs. Materials and Methods. We examined the incidence, prevalence, and risk factors for vulvovaginal candidiasis among a cohort of 898 women in south India. Participants completed three study visits over six months, comprised of a structured interview and a pelvic examination. Results. The positive predictive values for diagnosis of vulvovaginal candidiasis using individual signs or symptoms were low (<19%). We did not find strong evidence for associations between sociodemographic characteristics and the prevalence of vulvovaginal candidiasis. Women clinically diagnosed with bacterial vaginosis had a higher prevalence of vulvovaginal candidiasis (Prevalence 12%, 95% CI 8.2, 15.8) compared to women assessed to be negative for bacterial vaginosis (Prevalence 6.5%, 95% 5.3, 7.6); however, differences in the prevalence of vulvovaginal candidiasis were not observed by the presence or absence of laboratory-confirmed bacterial vaginosis. Conclusions. For correct diagnosis of vulvovaginal candidiasis, laboratory confirmation of infection with Candida is necessary as well as assessment of whether the discharge has been caused by bacterial vaginosis. Studies are needed of women infected with Candida yeast species to determine the risk factors for yeast’s overgrowth.