History behind the IVF egg: Are women's comprehensive histories associated with the number of eggs collected, or fertilised normally, from repeated IVF cycles? [abstract]

Most studies of in vitro fertilisation (IVF) outcomes use cycle-based data and fail to account for women who use repeated IVF cycles. The objective of this study was to examine the association between the number of eggs collected (EC) and the percentage fertilised normally, and women’s self-reported medical, personal and social histories. This study involved a crosssectional survey of infertile women (aged 27-46 years) recruited from four privately-owned fertility clinics located in major cities of Australia. Regression modeling was used to estimate the mean EC and mean percentage of eggs fertilised normally: adjusted for age at EC. Appropriate statistical methods were used to take account of repeated IVF cycles by the same women. Among 121 participants who returned the survey and completed 286 IVF cycles, the mean age at EC was 35.2 years (SD 4.5). Women’s age at EC was strongly associated with the number of EC: <30 years, 11.7 EC; 30.0-< 35 years, 10.6 EC; 35.0-<40.0 years, 7.3 EC; 40.0+ years, 8.1 EC; p<.0001. Prolonged use of oral contraceptives was associated with lower numbers of EC: never used, 14.6 EC; 0-2 years, 11.7 EC; 3-5 years, 8.5 EC; 6þ years, 8.2 EC; p=.04. Polycystic ovary syndrome (PCOS) was associated with more EC: have PCOS, 11.5 EC; no, 8.3 EC; p=.01. Occupational exposures may be detrimental to normal fertilisation: professional roles, 58.8%; trade and service roles, 51.8%; manual and other roles, 63.3%; p=.02. In conclusion, women’s age remains the most significant characteristic associated with EC but not the percentage of eggs fertilised normally.

Infertility resolved with or without fertility treatment in Australian women aged 31-36 years: A prospective, population-based study [abstract]

Birth outcomes during a three year period were compared for women with a history of infertility who did or did not use fertility treatment with hormones and/or in vitro fertilisation. Participants in the Australian Longitudinal Study on Women’s Health born in 1973-78 were randomly selected from the universal public health insurance database and completed up to five mailed surveys (1996-2009). Participants reported on their infertility and use of treatment at age 28-33 years (survey 4 (S4) in 2006) and 31-36 years (survey 5 (S5) in 2009). The odds of resolved infertility at S5 were estimated using logistic regression with adjustment for age, area of residence, private health insurance and male infertility. Among 7280 women who responded to both S4 and S5, 18.6% (n=1378) reported infertility. More than half (n=804, 56.8%) of these women did not use treatment and 43.9% (n=347) gave birth between S4 and S5. Compared to infertile women who did not use treatment, women who used treatment were more likely at S5 to have recently given birth (odds ratio (OR) = 1.59, 95% CI 1.26-2.00) or be pregnant (OR = 1.77, 1.27-2.46). Further, women who used treatment were more likely to have twins (3.37, 1.18-9.62), premature births (1.52, 0.95-2.43), or low birthweight babies (1.83, 0.70-2.53) compared to women who gave birth without using treatment. Many women aged up to 36 years with a history of infertility can conceive naturally over a three year period without the use of treatment.Women who have never had a prior birth may need to use treatment to resolve their infertility but they are at higher risk of poorer perinatal outcomes, such as premature or low birthweight babies.

Contraceptive changes after reproductive events among Australian women born in 1973 to 1978: A longitudinal study from 1996 to 2009

Background Women change contraception as they try to conceive, space births, and limit family size. This longitudinal analysis examines contraception changes after reproductive events such as birth, miscarriage or termination among Australian women born from 1973 to 1978 to identify potential opportunities to increase the effectiveness of contraceptive information and service provision. Methods Between 1996 and 2009, 5,631 Australian women randomly sampled from the Australian universal health insurance (Medicare) database completed five self-report postal surveys. Three longitudinal logistic regression models were used to assess the associations between reproductive events (birth only, birth and miscarriage, miscarriage only, termination only, other multiple events, and no new event) and subsequent changes in contraceptive use (start using, stop using, switch method) compared with women who continued to use the same method. Results After women experienced only a birth, or a birth and a miscarriage, they were more likely to start using contraception. Women who experienced miscarriages were more likely to stop using contraception. Women who experienced terminations were more likely to switch methods. There was a significant interaction between reproductive events and time indicating more changes in contraceptive use as women reach their mid-30s. Conclusion Contraceptive use increases after the birth of a child, but decreases after miscarriage indicating the intention for family formation and spacing between children. Switching contraceptive methods after termination suggests these pregnancies were unintended and possibly due to contraceptive failure. Women’s contact with health professionals around the time of reproductive events provides an opportunity to provide contraceptive services.

Challenges for researchers investigating contraceptive use and pregnancy intentions of young women living in urban and rural Australia : face-to-face discussions to increase participation in a web-based survey

Background: It is imperative to understand how to engage young women in research about issues that are important to them. There is limited reliable data on how young women access contraception in Australia especially in rural areas where services may be less available. Objective: This paper identifies the challenges involved in engaging young Australian women aged 18-23 years to participate in a web-based survey on contraception and pregnancy and ensure their ongoing commitment to follow-up web-based surveys. Methods: A group of young women, aged 18-23 years and living in urban and rural New South Wales, Australia, were recruited to participate in face-to-face discussions using several methods of recruitment: direct contact (face-to-face, telephone or email)and snowball sampling by potential participants inviting their friends. All discussions were transcribed verbatim and analyzed using thematic analysis. Results: Twenty young women participated (urban, n=10: mean age 21.6 years; rural, n=10: 20.0 years) and all used computers or smart phones to access the internet on a daily basis. All participants were concerned about the cost of internet access and utilized free access to social media on their mobile phones. Their willingness to participate in a web-based survey was dependent on incentives with a preference for small financial rewards. Most participants were concerned about their personal details and survey responses remaining confidential and secure. The most appropriate survey would take up to 15 minutes to complete, be a mix of short and long questions and eye-catching with bright colours. Questions on the sensitive topics of sexual activity, contraception and pregnancy were acceptable if they could respond with “I prefer not to answer”. Conclusions: There are demographic, participation and survey design challenges in engaging young women in a web-based survey. Based on our findings, future research efforts are needed to understand the full extent of the role social media and incentives play in the decision of young women to participate in web-based research.

Agreement between self-reported use of in vitro fertilization or ovulation induction, and medical insurance claims in Australian women aged 28–36 years

STUDY QUESTION: What is the self-reported use of in vitro fertilization (IVF) and ovulation induction (OI) in comparison with insurance claims by Australian women aged 28–36 years? SUMMARY ANSWER: The self-reported use of IVF is quite likely to be valid; however, the use of OI is less well reported. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Population-based research often relies on the self-reported use of IVF and OI because access to medical records can be difficult and the data need to include sufficient personal identifying information for linkage to other data sources. There have been few attempts to explore the reliability of the self-reported use of IVF and OI using the linkage to medical insurance claims for either treatment. STUDY DESIGN: This prospective, population-based, longitudinal study included the cohort of women born during 1973–1978 and participating in the Australian Longitudinal Study on Women's Health (ALSWH) (n = 14247). From 1996 to 2009, participants were surveyed up to five times. PARTICIPANTS AND SETTING: Participants self-reported their use of IVF or OI in two mailed surveys when aged 28–33 and 31–36 years (n = 7280), respectively. This study links self-report survey responses and claims for treatment or medication from the universal national health insurance scheme (i.e. Medicare Australia). MAIN RESULTS AND THE ROLE OF CHANCE: Comparisons between self-reports and claims data were undertaken for all women consenting to the linkage (n = 3375). The self-reported use of IVF was compared with claims for OI for IVF (Kappa, K = 0.83), oocyte collection (K = 0.82), sperm preparation (K = 0.83), intracytoplasmic sperm injection (K = 0.40), fresh embryo transfers (K = 0.82), frozen embryo transfers (K = 0.64) and OI for IVF medication (K = 0.17). The self-reported use of OI was compared with ovulation monitoring (K = 0.52) and OI medication (K = 0.71). BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION: There is a possibility of selection bias due to the inclusion criteria for participants in this study: (1) completion of the last two surveys in a series of five and (2) consent to the linkage of their responses with Medicare data. GENERALIZABILITY TO OTHER POPULATIONS: The results are relevant to questionnaire-based research studies with infertile women in developed countries. STUDY FUNDING/COMPETING INTEREST(S): ALSWH is funded by the Australian Government Department of Health and Ageing. This research is funded by a National Health and Medical Research Council Centre of Research Excellence grant.

Birth outcomes after spontaneous or assisted conception among infertile Australian women aged 28 to 36 years: A prospective, population-based study

Objective To examine the extent to which the odds of birth, pregnancy, or adverse birth outcomes are higher among women aged 28 to 36 years who use fertility treatment compared with untreated women. Design Prospective, population-based. Setting Not applicable. Patient(s) Participants in the ALSWH born in 1973 to 1978 who reported on their infertility and use of in vitro fertilization (IVF) or ovulation induction (OI). Intervention(s) Postal survey questionnaires administered as part of ALSWH. Main Outcome Measure(s) Among women treated with IVF or OI and untreated women, the odds of birth outcomes estimated by use of adjusted logistic regression modeling. Result(s) Among 7,280 women, 18.6% (n = 1,376) reported infertility. Half (53.0%) of the treated women gave birth compared with 43.8% of untreated women. Women with prior parity were less likely to use IVF compared with nulliparous women. Women using IVF or OI, respectively, were more likely to have given birth after treatment or be pregnant compared with untreated women. Women using IVF or OI were as likely to have ectopic pregnancies, stillbirths, or premature or low birthweight babies as untreated women. Conclusion(s) More than 40% of women aged 28–36 years reporting a history of infertility can achieve births without using treatment, indicating they are subfertile rather than infertile.

Miscarriage, preterm delivery, and stillbirth: Large variations in rates within a cohort of Australian women

Objectives We aimed to use simple clinical questions to group women and provide their specific rates of miscarriage, preterm delivery, and stillbirth for reference. Further, our purpose was to describe who has experienced particularly low or high rates of each event. Methods Data were collected as part of the Australian Longitudinal Study on Women's Health, a national prospective cohort. Reproductive histories were obtained from 5806 women aged 31–36 years in 2009, who had self-reported an outcome for one or more pregnancy. Age at first birth, number of live births, smoking status, fertility problems, use of in vitro fertilisation (IVF), education and physical activity were the variables that best separated women into groups for calculating the rates of miscarriage, preterm delivery, and stillbirth. Results Women reported 10,247 live births, 2544 miscarriages, 1113 preterm deliveries, and 113 stillbirths. Miscarriage was correlated with stillbirth (r = 0.09, P<0.001). The calculable rate of miscarriage ranged from 11.3 to 86.5 miscarriages per 100 live births. Women who had high rates of miscarriage typically had fewer live births, were more likely to smoke and were more likely to have tried unsuccessfully to conceive for ≥12 months. The highest proportion of live preterm delivery (32.2%) occurred in women who had one live birth, had tried unsuccessfully to conceive for ≥12 months, had used IVF, and had 12 years education or equivalent. Women aged 14–19.99 years at their first birth and reported low physical activity had 38.9 stillbirths per 1000 live births, compared to the lowest rate at 5.5 per 1000 live births. Conclusion Different groups of women experience vastly different rates of each adverse pregnancy event. We have used simple questions and established reference data that will stratify women into low- and high-rate groups, which may be useful in counselling those who have experienced miscarriage, preterm delivery, or stillbirth, plus women with fertility intent.

The Authority of Influence : Women and Power in Burmese History

This book explores the relationship between gender and power in Burmese history from pre-colonial times to the present day and aims to identify the sources, nature and limitations of women’s power. The study takes as its starting point the apparent contradiction that, though Burmese women historically enjoyed relatively high social status and economic influence, for the most part they remained conspicuously absent from positions of authority in formal religious, social and political institutions. The book thus examines the concept of ‘family’ in Burmese political culture, and reveals how some women were able to gain political influence through their familial connections with powerful men, even while cultural models of ‘correct’ female behaviour prevented most women from attaining official positions of political authority. The study also considers how various influences – Buddhism, colonialism, nationalism, modernisation and militarism – shaped Burmese concepts of gender and power, with important implications for how women were able to exercise social, economic and political influence. The book explores how the effects of prolonged armed conflict, economic isolation and political oppression have constrained opportunities for women to attain power in contemporary Burma, and examines opportunities opened up by the pro-democracy movement and recent focus on women's issues and rights for women to exercise influence both inside Burma and in exile. Using an interdisciplinary approach that draws on feminist, anthropological and social science discourses, placing them within an historical framework, the author offers a broad understanding of how power is obtained and exercised in Burma in order to reassess historical representations of Burmese women and so provide a more comprehensive and inclusive understanding of power relations in historical and contemporary Burma.

Akt, AS160, metabolic risk factors and aerobic fitness in middle-aged women

Aims: This study investigated the association between the basal (rest) insulin-signaling proteins, Akt, and the Akt substrate AS160, metabolic risk factors, inflammatory markers and aerobic fitness, in middle-aged women with varying numbers of metabolic risk factors for type 2 diabetes. Methods: Sixteen women (n = 16) aged 51.3+/-5.1 (mean +/-SD) years provided muscle biopsies and blood samples at rest. In addition, anthropometric characteristics and aerobic power were assessed and the number of metabolic risk factors for each participant was determined (IDF criteria). Results: The mean number of metabolic risk factors was 1.6+/-1.2. Total Akt was negatively correlated with IL-1 beta (r = -0.45, p = 0.046), IL-6 (r = -0.44, p = 0.052) and TNF-alpha (r = -0.51, p = 0.025). Phosphorylated AS160 was positively correlated with HDL (r = 0.58, p = 0.024) and aerobic fitness (r = 0.51, p = 0.047). Furthermore, a multiple regression analysis revealed that both HDL (t = 2.5, p = 0.032) and VO(2peak) (t = 2.4, p = 0.037) were better predictors for phosphorylated AS160 than TNF-alpha or IL-6 (p>0.05). Conclusions: Elevated inflammatory markers and increased metabolic risk factors may inhibit insulin-signaling protein phosphorylation in middle-aged women, thereby increasing insulin resistance under basal conditions. Furthermore, higher HDL and fitness levels are associated with an increased AS160 phosphorylation, which may in turn reduce insulin resistance.

The relationship between drivers’ perceptions toward police speed enforcement and self-reported speeding behaviour

Exceeding the speed limit and driving too fast for the conditions are regularly cited as significant contributing factors in traffic crashes, particularly fatal and serious injury crashes. Despite an extensive body of research highlighting the relationship between increased vehicle speeds and crash risk and severity, speeding remains a pervasive behaviour on Australian roads. The development of effective countermeasures designed to reduce the prevalence of speeding behaviour requires that this behaviour is well understood. The primary aim of this program of research was to develop a better understanding of the influence of drivers’ perceptions and attitudes toward police speed enforcement on speeding behaviour. Study 1 employed focus group discussions with 39 licensed drivers to explore the influence of perceptions relating to specific characteristics of speed enforcement policies and practices on drivers’ attitudes towards speed enforcement. Three primary factors were identified as being most influential: site selection; visibility; and automaticity (i.e., whether the enforcement approach is automated/camera-based or manually operated). Perceptions regarding these enforcement characteristics were found to influence attitudes regarding the perceived legitimacy and transparency of speed enforcement. Moreover, misperceptions regarding speed enforcement policies and practices appeared to also have a substantial impact on attitudes toward speed enforcement, typically in a negative direction. These findings have important implications for road safety given that prior research has suggested that the effectiveness of speed enforcement approaches may be reduced if efforts are perceived by drivers as being illegitimate, such that they do little to encourage voluntary compliance. Study 1 also examined the impact of speed enforcement approaches varying in the degree of visibility and automaticity on self-reported willingness to comply with speed limits. These discussions suggested that all of the examined speed enforcement approaches (see Section 1.5 for more details) generally showed potential to reduce vehicle speeds and encourage compliance with posted speed limits. Nonetheless, participant responses suggested a greater willingness to comply with approaches operated in a highly visible manner, irrespective of the corresponding level of automaticity of the approach. While less visible approaches were typically associated with poorer rates of driver acceptance (e.g., perceived as “sneaky” and “unfair”), participants reported that such approaches would likely encourage long-term and network-wide impacts on their own speeding behaviour, as a function of the increased unpredictability of operations and increased direct (specific deterrence) and vicarious (general deterrence) experiences with punishment. Participants in Study 1 suggested that automated approaches, particularly when operated in a highly visible manner, do little to encourage compliance with speed limits except in the immediate vicinity of the enforcement location. While speed cameras have been criticised on such grounds in the past, such approaches can still have substantial road safety benefits if implemented in high-risk settings. Moreover, site-learning effects associated with automated approaches can also be argued to be a beneficial by-product of enforcement, such that behavioural modifications are achieved even in the absence of actual enforcement. Conversely, manually operated approaches were reported to be associated with more network-wide impacts on behaviour. In addition, the reported acceptance of such methods was high, due to the increased swiftness of punishment, ability for additional illegal driving behaviours to be policed and the salutary influence associated with increased face-to-face contact with authority. Study 2 involved a quantitative survey conducted with 718 licensed Queensland drivers from metropolitan and regional areas. The survey sought to further examine the influence of the visibility and automaticity of operations on self-reported likelihood and duration of compliance. Overall, the results from Study 2 corroborated those of Study 1. All examined approaches were again found to encourage compliance with speed limits, such that all approaches could be considered to be “effective”. Nonetheless, significantly greater self-reported likelihood and duration of compliance was associated with visibly operated approaches, irrespective of the corresponding automaticity of the approach. In addition, the impact of automaticity was influenced by visibility; such that significantly greater self-reported likelihood of compliance was associated with manually operated approaches, but only when they are operated in a less visible fashion. Conversely, manually operated approaches were associated with significantly greater durations of self-reported compliance, but only when they are operated in a highly visible manner. Taken together, the findings from Studies 1 and 2 suggest that enforcement efforts, irrespective of their visibility or automaticity, generally encourage compliance with speed limits. However, the duration of these effects on behaviour upon removal of the enforcement efforts remains questionable and represents an area where current speed enforcement practices could possibly be improved. Overall, it appears that identifying the optimal mix of enforcement operations, implementing them at a sufficient intensity and increasing the unpredictability of enforcement efforts (e.g., greater use of less visible approaches, random scheduling) are critical elements of success. Hierarchical multiple regression analyses were also performed in Study 2 to investigate the punishment-related and attitudinal constructs that influence self-reported frequency of speeding behaviour. The research was based on the theoretical framework of expanded deterrence theory, augmented with three particular attitudinal constructs. Specifically, previous research examining the influence of attitudes on speeding behaviour has typically focussed on attitudes toward speeding behaviour in general only. This research sought to more comprehensively explore the influence of attitudes by also individually measuring and analysing attitudes toward speed enforcement and attitudes toward the appropriateness of speed limits on speeding behaviour. Consistent with previous research, a number of classical and expanded deterrence theory variables were found to significantly predict self-reported frequency of speeding behaviour. Significantly greater speeding behaviour was typically reported by those participants who perceived punishment associated with speeding to be less certain, who reported more frequent use of punishment avoidance strategies and who reported greater direct experiences with punishment. A number of interesting differences in the significant predictors among males and females, as well as younger and older drivers, were reported. Specifically, classical deterrence theory variables appeared most influential on the speeding behaviour of males and younger drivers, while expanded deterrence theory constructs appeared more influential for females. These findings have important implications for the development and implementation of speeding countermeasures. Of the attitudinal factors, significantly greater self-reported frequency of speeding behaviour was reported among participants who held more favourable attitudes toward speeding and who perceived speed limits to be set inappropriately low. Disappointingly, attitudes toward speed enforcement were found to have little influence on reported speeding behaviour, over and above the other deterrence theory and attitudinal constructs. Indeed, the relationship between attitudes toward speed enforcement and self-reported speeding behaviour was completely accounted for by attitudes toward speeding. Nonetheless, the complexity of attitudes toward speed enforcement are not yet fully understood and future research should more comprehensively explore the measurement of this construct. Finally, given the wealth of evidence (both in general and emerging from this program of research) highlighting the association between punishment avoidance and speeding behaviour, Study 2 also sought to investigate the factors that influence the self-reported propensity to use punishment avoidance strategies. A standard multiple regression analysis was conducted for exploratory purposes only. The results revealed that punishment-related and attitudinal factors significantly predicted approximately one fifth of the variance in the dependent variable. The perceived ability to avoid punishment, vicarious punishment experience, vicarious punishment avoidance and attitudes toward speeding were all significant predictors. Future research should examine these relationships more thoroughly and identify additional influential factors. In summary, the current program of research has a number of implications for road safety and speed enforcement policy and practice decision-making. The research highlights a number of potential avenues for the improvement of public education regarding enforcement efforts and provides a number of insights into punishment avoidance behaviours. In addition, the research adds strength to the argument that enforcement approaches should not only demonstrate effectiveness in achieving key road safety objectives, such as reduced vehicle speeds and associated crashes, but also strive to be transparent and legitimate, such that voluntary compliance is encouraged. A number of potential strategies are discussed (e.g., point-to-point speed cameras, intelligent speed adaptation. The correct mix and intensity of enforcement approaches appears critical for achieving optimum effectiveness from enforcement efforts, as well as enhancements in the unpredictability of operations and swiftness of punishment. Achievement of these goals should increase both the general and specific deterrent effects associated with enforcement through an increased perceived risk of detection and a more balanced exposure to punishment and punishment avoidance experiences.

A prospective study of pregnancy weight gain in Australian women

Background: While weight gain during pregnancy is regarded as important, there has not been a prospective study of measured weight gain in pregnancy in Australia. This study aimed to prospectively evaluate pregnancy-related weight gain against the Institute of Medicine (IOM) recommendations in women receiving antenatal care in a setting where ongoing weight monitoring is not part of routine clinical practice, to describe women's knowledge of weight gain recommendations and to describe the health professional advice received relating to gestational weight gain (GWG). Methods: Pregnant women were recruited ≤20 weeks of gestation (n = 664) from a tertiary obstetric hospital between August 2010 to July 2011 for this prospective observational study. Outcome measures were weight gain from pre-pregnancy to 36 weeks of gestation, weight gain knowledge and health professional advice received. Results: Thirty-six percent of women gained weight according to guidelines. Twenty-six percent gained inadequate weight, and 38% gained excess weight. Fifty-six percent of overweight women gained weight in excess of the IOM guidelines compared with 30% of those who started with a healthy weight (P < 0.001). At 16 weeks, 47% of participants were unsure of the weight gain recommendations for them. Sixty-two percent of women reported that the health professionals caring for them during this pregnancy ‘never’ or ‘rarely’ offered advice about how much weight to gain. Conclusions: The prevalence of inappropriate gestational weight gain in this study was high. The majority of women do not know their recommended weight gain. The advice women received from health professionals relating to healthy weight gain in pregnancy could be improved.

Weight gain and nutritional intake in obese pregnant women : some clues for intervention

Aim:  Maternal obesity is associated with increased risk of adverse outcomes for mothers and offspring. Strategies to better manage maternal obesity are urgently needed; however, there is little evidence to assist the development of nutrition interventions during antenatal care. The present study aimed to assess maternal weight gain and dietary intakes of overweight and obese women participating in an exercise trial. Results will assist the development of interventions for the management of maternal overweight and obesity. Methods:  Fifty overweight and obese pregnant women receiving antenatal care were recruited and provided dietary and weight data at baseline (12 weeks), 28 weeks, 36 weeks gestation and 6 weeks post-partum. Data collected were compared with current nutritional and weight gain recommendations. Associations used Pearson's correlation coefficient, and ANOVA assessed dietary changes over time, P < 0.05. Results:  Mean prepregnancy body mass index was 34.4 ± 6.6 kg/m2. Gestational weight gain was 10.6 ± 6 kg with a wide range (−4.1 to 23.0 kg). 52% of women gained excessive weight (>11.5 kg for overweight and >9 kg for obese women). Gestational weight gain correlated with post-partum weight retention (P < 0.001). Dietary intakes did not change significantly during pregnancy. No women achieved dietary fat or dietary iron recommendations, only 11% achieved adequate dietary folate, and 38% achieved adequate dietary calcium. Very few women achieved recommended food group servings for pregnancy, with 83% consuming excess servings of non-core foods. Conclusion:  Results provide evidence that early intervention and personalised support for obese pregnant women may help achieve individualised goals for maternal weight gain and dietary adequacy, but this needs to be tested in a clinical setting.

Comparison of cervical and blood T-cell responses to human papillomavirus-16 in women with human papillomavirus-associated cervical intraepithelial neoplasia

Human papillomaviruses (HPVs) are obligate epithelial pathogens and typically cause localized mucosal infections. We therefore hypothesized that T-cell responses to HPV antigens would be greater at sites of pathology than in the blood. Focusing on HPV-16 because of its association with cervical cancer, the magnitude of HPV-specific T-cell responses at the cervix was compared with those in the peripheral blood by intracellular cytokine staining following direct ex vivo stimulation with both virus-like particles assembled from the major capsid protein L1, and the major HPV oncoprotein, E7. We show that both CD4 + and CD8 + T cells from the cervix responded to the HPV-16 antigens and that interferon-γ (IFN-γ) production was HPV type-specific. Comparing HPV-specific T-cell IFN-γ responses at the cervix with those in the blood, we found that while CD4 + and CD8 + T-cell responses to L1 were significantly correlated between compartments (P = 0.02 and P = 0.05, respectively), IFN-γ responses in both T-cell subsets were significantly greater in magnitude at the cervix than in peripheral blood (P = 0.02 and P = 0.003, respectively). In contrast, both CD4 + and CD8 + T-cell IFN-γ responses to E7 were of similar magnitude in both compartments and CD8 + responses were significantly correlated between these distinct immunological compartments (P = 0.04). We therefore show that inflammatory T-cell responses against L1 (but not E7) demonstrate clear compartmental bias and the magnitude of these responses do reflect local viral replication but that correlation of HPV-specific responses between compartments indicates their linkage.

More men than women make mucosal IgA antibodies to human papillomavirus type 16 (HPV-16) and HPV-18: A study of oral HPV and oral HPV antibodies in a normal healthy population

Background: We have previously shown the high prevalence of oral anti-human papillomavirus type 16 (HPV-16) antibodies in women with HPV-associated cervical neoplasia. It was postulated that the HPV antibodies were initiated after HPV antigenic stimulation at the cervix via the common mucosal immune system. The present study aimed to further evaluate the effectiveness of oral fluid testing for detecting the mucosal humoral response to HPV infection and to advance our limited understanding of the immune response to HPV. Methods: The prevalence of oral HPV infection and oral antibodies to HPV types 16, 18 and 11 was determined in a normal, healthy population of children, adolescents and adults, both male and female, attending a dental clinic. HPV types in buccal cells were determined by DNA sequencing. Oral fluid was collected from the gingival crevice of the mouth by the OraSure method. HPV-16, HPV-18 and HPV-11 antibodies in oral fluid were detected by virus-like particle-based enzyme-linked immunosorbent assay. As a reference group 44 women with cervical neoplasia were included in the study. Results: Oral HPV infection was h ighest in children (9/114, 7.9%), followed by adolescents (4/78, 5.1%), and lowest in normal adults (4/116, 3.5%). The predominant HPV type found was HPV-13 (7/22, 31.8%) followed by HPV-32 (5/22, 22.7%). The prevalence of oral antibodies to HPV-16, HPV-18 and HPV-11 was low in children and increased substantially in adolescents and normal adults. Oral HPV-16 IgA was significantly more prevalent in women with cervical neoplasia (30/44, 68.2%) than the women from the dental clinic (18/69, 26.1% P = 0.0001). Significantly more adult men than women displayed oral HPV-16 IgA (30/47 compared with 18/69, OR 5.0, 95% CI 2.09-12.1, P < 0.001) and HPV-18 IgA (17/47 compared with 13/69, OR 2.4, 95% CI 0.97-6.2, P = 0.04). Conclusion: The increased prevalence of oral HPV antibodies in adolescent individuals compared with children was attributed to the onset of sexual activity. The increased prevalence of oral anti-HPV IgA in men compared with women was noteworthy considering reportedly fewer men than women make serum antibodies, and warrants further investigation. © 2006 Marais et al; licensee BioMed Central Ltd.