Options for change in the Australian cervical cancer screening program in context of HPV detection and vaccination

Introduction:
Cervical cancer screening has been implemented for over a decade in Australia and has significantly reduced the mortality and morbidity of the disease. The emergence of new technologies for cervical cancer, such as the Human Papillomavirus (HPV) vaccine and DNA testing has encouraged debate regarding the effective use of resources in cervical cancer prevention. The present study evaluates the cost-effectiveness, from a health sector perspective, of various screening strategies in the era of these new technologies.

Methods:
A stochastic epidemiological model using a discrete event and continuous algorithm was developed to describe the natural history of cervical cancer. By allowing one member of the cohort into the model at a time, this micro-simulation model encompasses the characteristics of heterogeneity and can track individual life histories. To evaluate the cost-effectiveness of the HPV vaccine a Markov model was built to simulate the effect on the incidence of HPV and subsequent cervical cancer. A number of proposed screening strategies were evaluated with the stochastic model for the application of HPV DNA testing, with changes in the screening interval and target population. Health outcomes were measured by Disability-Adjusted Life-Years (DALYs), adjusted for application within an evaluation setting (i.e. the mortality component of the DALY was adjusted by a disability weight when early mortality due to cervical cancer is avoided). Costs in complying with the Australian updated guidelines were assessed by pathway analysis to estimate the resources associated with cervical cancer and its pre-cancerous lesion treatment. Sensitivity analyses were performed to investigate the key parameters that influenced the cost-effectiveness results.

Results:
Current practice has already brought huge health gain by preventing more than 4,000 deaths and saving more than 86,000 life-years in a cohort of a million women. Any of the alternative screening strategies alter the total amount of health gain by a small margin compared to current practice. The results of incremental analyses of the alternative screening strategies compared to current practice suggest the adoption of the HPV DNA test as a primary screening tool every 3 years commencing at age 18, or the combined pap smear/HPV test every 3 years commencing at age 25, are more costly than current practice but with reasonable ICERs (AUD$1,810 per DALY and AUD$18,600 per DALY respectively). Delaying commencement of Pap test screening to age 25 is less costly than current practice, but involves considerable health loss. The sensitivity analysis shows, however, that the screening test accuracy has a significant impact on these conclusions. Threshold analysis indicates that a sensitivity ranging from 0.80 to 0.86 for the combined test in women younger than 30 is required to produce an acceptable incremental cost-effectiveness ratio.

Conclusions:
The adoption of HPV and combined test with an extended screening interval is more costly but affordable, resulting in reasonable ICERs. They appear good value for money for the Australian health care system, but need more information on test accuracy to make an informed decision. Potential screening policy change under current Australian HPV Vaccination Program is current work in progress. A Markov model is built to simulate the effect on the incidence of HPV and subsequent cervical cancer. Adoption of HPV DNA test as a primary screening tool in the context of HPV vaccination is under evaluation.

Oxidised mannan-listeriolysin O conjugates induce Th1/Th2 cytokine responses after intranasal immunisation

Clearance of infectious organisms does not always require polarised Th1 or Th2 responses and it may be advantageous for both Th1 and Th2 responses to be elicited for effective protection against an invading pathogen. It was the aim of this study to investigate oxidised mannan as a possible Th1/Th2 adjuvant. Oxidised mannan was conjugated to two candidate antigens and delivered intranasally to mice. Immunisation with the oxidised conjugate resulted in significant antigen specific proliferative responses, IL-2, IFN-γ and IL-4 production when compared to unconjugated controls.

Knowledge of human papillomavirus (HPV) and the HPV vaccine in a national sample of Australian men and women

Background: Human papillomavirus (HPV) knowledge has rarely been investigated in the context of a national vaccination program. The present study investigated HPV knowledge after the introduction of a national HPV vaccination program in Australia using a national sample of men and women. Methods: Questions assessing HPV knowledge were part of a broader national study of health and relationships administered via a computer-assisted telephone interview. These findings are from wave four of the study, conducted between 2007 and 2008. Knowledge questions about HPV included its association with cervical cancer, genital warts and abnormal Pap tests. Results: A total of 2634 women and 2556 men between the ages of 18 and 70 were interviewed. Overall, 62.8% (95% confidence interval (CI): 60.8–64.7%) of women and 38.3% (95% CI: 36.3–40.4%) of men had heard of HPV. Of these, 66.0% (95% CI: 64.1–67.9%) correctly answered that HPV is associated with cervical cancer, 50.2% (95% CI: 48.2–52.1%) answered that HPV is associated with abnormal Pap tests and 44.5% (95% CI:42.5–46.5%) answered that HPV causes warts. Predictors of good knowledge included being female, aged between 26 and 45, holding higher education levels and older age at first sex. Ever having a Pap test was also associated with awareness about HPV. Conclusion: One of the highest levels of knowledge about HPV in Australia to date is reported in the present study. Knowledge about the association between HPV and cervical cancer was particularly high, especially when compared with knowledge of the association with genital warts. This appears to be a consequence of the marketing of the HPV vaccine as a vaccination against cervical cancer.

The immunisation controversy as an illustration of who we are

This seminar paper enlists the controversy about vaccination in an attempt to illustrate how human subjectivity can be said to be always created discursively. It suggests how these discourses are often manipulated along irrational lines.

Sucrose and lollypops to reduce immunisation pain in toddlers and young children: two pilot randomised controlled trials

Aims To evaluate the feasibility, acceptability and preliminary efficacy of sweet taste in reducing pain in toddlers and pre-school children during immunisation and to use the results to inform a sample size estimation for future full-scale trials. Background Sweet solutions reduce procedural pain in newborn infants and in infants beyond the newborn period. It is unclear if sweet taste continues to reduce procedural pain in children older than one year of age. Design Two parallel design pilot randomised controlled trials (RCTs). Methods Children attending an Immunisation Drop-in Clinic at a children's hospital in Australia participated in one of two pilot RCTs: 1) a double-blinded RCT of 33% sucrose compared to water in toddlers receiving their 12- or 18-month immunisation or 2) a non-blinded RCT of lollypop compared to standard care (active distraction using bubble and pin wheel blowing) in pre-school children aged 3-5 years. Primary outcomes included cry incidence and duration and pain score using the FLACC. Results Interventions, standard care and all aspects of the study were acceptable to children, parents and immunisation nurses. More toddlers in the sucrose group received their 12-month immunisation and more injections (n=35) compared to toddlers randomised to water (n=26). There were no significant differences in crying time or pain scores between intervention and control groups in either pilot RCT. Conclusion The study interventions are acceptable to children and parents. Full-scale trials would be feasible to conduct. Implications for clinical practice Toddlers receiving their 12-month immunisation should be the focus of future full-scale RCTs.

Effect of self-collection of HPV DNA offered by community health workers at home visits on uptake of screening for cervical cancer (the EMA study): a population-based cluster-randomised trial

Control of cervical cancer in developing countries has been hampered by a failure to achieve high screening uptake. HPV DNA self-collection could increase screening coverage, but implementation of this technology is difficult in countries of middle and low income. We investigated whether offering HPV DNA self-collection during routine home visits by community health workers could increase cervical screening.

HPV.edu study protocol: a cluster randomised controlled evaluation of education, decisional support and logistical strategies in school-based human papillomavirus (HPV) vaccination of adolescents

BACKGROUND: The National Human Papillomavirus (HPV) Vaccination Program in Australia commenced in 2007 for females and in 2013 for males, using the quadrivalent HPV vaccine (HPV 6,11,16,18). Thus far, we have demonstrated very substantial reductions in genital warts and in the prevalence of HPV among young Australian women, providing early evidence for the success of this public health initiative. Australia has a long history of school-based vaccination programs for adolescents, with comparatively high coverage. However, it is not clear what factors promote success in a school vaccination program. The HPV.edu study aims to examine: 1) student knowledge about HPV vaccination; 2) psycho-social outcomes and 3) vaccination uptake.

METHODS/DESIGN: HPV.edu is a cluster randomised trial of a complex intervention in schools aiming to recruit 40 schools with year-8 enrolments above 100 students (approximately 4400 students). The schools will be stratified by Government, Catholic, and Independent sectors and geographical location, with up to 20 schools recruited in each of two states, Western Australia (WA) and South Australia (SA), and randomly allocated to intervention or control (usual practice). Intervention schools will receive the complex intervention which includes an adolescent intervention (education and distraction); a decisional support tool for parents and adolescents and logistical strategies (consent form returns strategies, in-school mop-up vaccination and vaccination-day guidelines). Careful process evaluation including an embedded qualitative evaluation will be undertaken to explore in depth possible mechanisms for any observed effect of the intervention on primary and secondary outcomes.

DISCUSSION: This study is the first to evaluate the relative effectiveness of various strategies to promote best practice in school-based vaccination against HPV. The study aims to improve vaccination-related psychosocial outcomes, including adolescent knowledge and attitudes, decision-making involvement, self-efficacy, and to reduce fear and anxiety. The study also aims to improve school vaccination program logistics including reduction in time spent vaccinating adolescents and increased number of consent forms returned (regardless of decision). Less anxiety in adolescents will likely promote more efficient vaccination, which will be more acceptable to teachers, nurses and parents. Through these interventions, it is hoped that vaccination uptake will be increased.

In the shadow of the volcanoes: the impact of intervention on the nutrition and health status of Rwandan refugee children in Zaire two years from the exodus

Objective: To evaluate the public health and nutritional situation of refugee children in Katale camp, Eastern Zaire, after two years of nutritional and health intervention from 1994 to 1996.
Design: Cross-sectional survey using a two-stage cluster sampling method. Anthropometric data were collected from 28 May 1996 to 4 June 1996. Retrospective review of food basket monitoring data over the preceding six months and the United Nations High Commission for Refugees' weekly mortality data was conducted. Measles immunisation coverage data were surveyed simultaneously, using child health records.
Main outcome measures: Nutritional status measured by weight-for-height index (W/H), measles immunisation status, average daily energy content of the general food ration and crude mortality rate.
Setting: Katale refugee camp, Zaire, June 1996.
Analysis: Weight-for-height index and proportion of immunised children were computed using EPINUT, part of EPINFO computer package.
Results: Malnutrition was found to be most prevalent in children aged six to 29 months old (W/H < -2 Z-score and/or oedema: 6.2%; 95% CI: 3.4%, 10.6%), among whom the malnutrition rate was almost double the overall malnutrition prevalence (W/H < -2 Z-score and/or oedema: 3.5% (95% CI: 1.5%, 7.2%). The general food ration, although conforming to the World Food Program minimum standards of adequacy in terms of variety (being composed of cereals, oil, beans, blended cereal and legume mixes and salt), provided only 6240 kJ on average (95% CI: 5040, 7140 kJ) per person per day, thus meeting only 57% to 84% of the minimum energy requirements for an adult, and falling well below the needs for sub groups with higher nutritional requirements such as children, pregnant and breastfeeding women and the sick. Measles immunisation coverage in children nine to 59 months was 88.6%. The crude mortality rate was found to be 0.3 per 10 000 per day. Refugees received 15 litres of clean water per person per day.
Conclusion: Public health interventions in Katale camp 1994 to 1996 had reduced mortality and morbidity rates dramatically. This was not reflected in the malnutrition rates for children under five years, that remained stable after an initial fall despite two years of nutritional intervention. The factors contributed to this were related to an inadequate general food ration (due to food shortages), lack of ability to supplement the diet, (due to economic restrictions that were imposed in the camp) and inequities in the food distribution process (due to food being siphoned off by camp leaders for military purposes).

Prevalence of genital human papillomavirus DNA in a sample of senior school-aged women in the Australian Capital Territory

Background: A strong association between persistent infection with oncogenic types of human papillomavirus (HPV) and cervical cancer is well established. Small numbers of international studies examining adolescent HPV infection and the risk factors associated are published, but there is currently no evidence on the prevalence and risk factors for HPV in an Australian, sexually active female adolescent population. Methods: To provide prevalence and risk factors for HPV in a female sexually active, senior high school population in the Australian Capital Territory (ACT), a convenience sample of 161, 16–19-year-old females attending a senior high school was evaluated. The sample formed part of a larger sample recruited for a study of sexually transmitted infections and blood-borne viruses in senior high school students. A clinical record was used to collect information about sexual and other risk behaviours, while self-collected vaginal swabs were tested for HPV DNA detection and genotyping using polymerase chain reaction. Results: The prevalence of HPV DNA in this sample overall was 11.2%, with multiple genotypes in 38%. No statistically significant associations were found between HPV DNA and the number of male partners, age of coitarche, time since first sexually active, condom use, smoking or alcohol intake. Conclusions: This is the first Australian study that has examined the prevalence and risk factors for genital HPV in this demographic group. The prevalence of HPV infection is slightly lower than reported in similar age groups overseas and is lower than other Australian studies in older women and those attending sexual health centres. Of HPV-positive young women, high-risk genotypes were found in over half, with more than one-third of HPV existing as multiple genotypes. Large community-based prevalence studies are needed to guide the development of recommendations for the vaccination of young women against HPV and to support other health promotion initiatives.

Effects of sexually transmitted infection status, relationship status, and disclosure status on sexual self-concept

Research has indicated that having a sexually transmitted infection (STI) such as genital herpes and genital human papilloma virus (HPV) can have a negative impact on an individual's sexuality. The current study was designed to evaluate the effect of STI status, relationship status, and disclosure status on various dimensions of sexual self-concept. A questionnaire that evaluated the above variables was completed by 117 individuals with genital herpes, 82 individuals with HPV, and 75 individuals with no STI. The results demonstrated that having herpes or HPV had a significant negative impact on aspects of sexual self-concept. It does not appear that an individual's relationship status is a factor associated with the impact of having an STI on the sexual self-concept. Respondents who had disclosed their STI to their partners, however, had significantly more positive feelings about aspects of their sexual self-concept than those who had not disclosed their STI to their partners. The implications of these research findings for health practitioners are discussed.

Sexually transmitted infections: Impact on individuals and their relationships

The impact of having genital herpes and genital human papilloma virus (HPV) on individuals and their relationships was investigated. A qualitative research methodology explored the lived experiences of 30 adults with genital herpes (15 men, 15 women), and 30 adults with HPV (15 men, 15 women). This study addressed individuals' feelings about the impact of stigma associated with having an STI, the impact of having an STI on sexuality and on intimate relationships, and feelings surrounding the process of disclosure. Implications of the findings for research and clinical practice are discussed.

Patterns of treatment of external genital warts in Australian sexual health clinics

Background: External genital warts are a common sexually transmitted viral disease. We describe the patterns of treatment for initial presentations of external genital warts (EGWs) in Australian sexual health centers.
Methods: This was a retrospective audit of 489 case notes from consecutive individuals who presented with a new diagnosis of EGWs to 1 of 5 major sexual health clinics in Australia. Eligibility criteria were consecutive patients aged 18 to 45 years inclusively, presenting with first ever episode of EGWs from January 1, 2004. Exclusion criteria were patients who were immunocompromised, including HIV infection, or enrollment in a treatment study for EGWs.
Results: The median age at presentation of women was 23.2 years and of men 26.8 years. One quarter (n = 127) of patients had another sexually transmitted infection diagnosed at presentation. Nearly half of the patients (n = 224) presented only once for treatment. Most often, patients were treated with a monotherapy (n = 382/489; 78%), usually cryotherapy (257; 53%). Staff applied treatment in 361 (74%) cases. There was wide variation across sites, possibly reflecting local policies and budgets. We found no difference in wart resolution (n = 292; 60%) by initial treatment chosen.
Conclusions: The diagnosis and treatment of genital warts constitute a sizable proportion of clinical visits to the audited sexual health services and require a large input of staff time to manage, including the application of topical treatments. Our results help complete the picture of the burden of EGWs on Australian sexual health centers before the introduction of the HPV vaccine.