Barriers and facilitators of cervical cancer screening literacy among rural women with HIV attending rural public health facilities in East Central Uganda: a qualitative study using the integrated model of health literacy.

BACKGROUND: Several rural public health facilities in East Central Uganda have sub-optimal, below 50%, levels of uptake of cervical cancer screening services among women with HIV. This is attributed to low cervical cancer screening literacy: limited ability to access, understand, appraise, and apply cervical cancer screening information. This research identified multi-level (health facility, community, interpersonal and individual) barriers, and facilitators of accessing, understanding, and applying cervical cancer screening information among rural women with HIV attending rural public health facilities in East Central Uganda to inform interventions. METHODS: We conducted ten Focus Group Discussions with rural women aged 25-49 years with HIV attending four selected rural public health facilities: thirty women who had ever screened for cervical cancer and thirty women who had never screened for cervical cancer across different age categories. Data was collected using a guide based on the Integrated model of health literacy. Thematic analysis was used for analysis. Competences (accessing, understanding and applying cervical cancer screening information) and categories of factors (health system, community, interpersonal and individual factors) of the integrated model of health literacy were deductively derived whereas barriers and facilitators were deductively derived from women's statements. RESULTS: Lack of communication materials and inability to access information were health facility and individual barriers of accessing cervical cancer screening information respectively. Facilitators of accessing information were access to information at health facility, community, and interpersonal levels and women's ability to access information. Barriers and facilitators of understanding cervical cancer information were related to communication materials, provision of health education and women's concentration during health education. Barriers and facilitators of applying cervical cancer screening information were related to communication and provision of cervical cancer screening services at health facility level, and interpersonal level from peers, partners and other family members as well as women's ability to: understand information and access to cervical cancer screening services at individual level. CONCLUSIONS: This study emphasizes the influence of multi-level factors on cervical cancer screening literacy among rural women with HIV attending rural public health facilities in East Central Uganda. Improving uptake of cervical cancer screening services among these women requires multi-level interventions.

Usability of a smartphone-compatible, confocal micro-endoscope for cervical cancer screening in resource-limited settings.

BACKGROUND: More efficient methods to detect and treat precancerous lesions of the cervix at a single visit, such as low-cost confocal microscopy, could improve early diagnosis and hence outcomes. We piloted a prototype smartphone-compatible confocal micro-endoscope (SCME) among women presenting to a public cervical cancer screening clinic in Kampala, Uganda. We describe the piloting of the SCME device at an urban clinic used by lower cadre staff. METHODS: We screened women aged 18 and 60 years, who presented for cervical cancer screening at the Kawempe National Referral Hospital Kampala, and evaluated the experience of their providers (nurses). Nurses received a 2-day training by the study doctors on how to use the SCME, which was added to the standard Visual Inspection with Acetic acid (VIA)-based cervical cancer screening. The SCME was used to take colposcopy images before and after VIA at positions 12 and 6 O'clock if VIA negative, and on precancer-suspicious lesions if VIA positive. We used questionnaires to assess the women's experiences after screening, and the experience of the nurses who operated the SCME. RESULTS: Between November 2021 and July 2022, we screened 291 women with a median age of 36 years and 65.7% were HIV positive. Of the women screened, 146 were eligible for VIA, 123 were screened with the SCME, and we obtained confocal images from 103 women. Of those screened with the SCME, 60% found it comfortable and 81% were willing to screen again with it. Confocal images from 79% of the women showed distinguishable cellular features, while images from the remaining 21% were challenging to analyze. Nurses reported a mean score of 85% regarding the SCME's usefulness to their work, 71% regarding their satisfaction and willingness to use it again, 63% in terms of ease of use, and 57% concerning the ease of learning how to operate the SCME. CONCLUSION: Our findings demonstrate the feasibility of using the SCME by lower cadre staff in low-resource settings to aid diagnosis of precancerous lesions. However, more work is needed to make it easier for providers to learn how to operate the SCME and capture high-quality confocal images.

Baseline knowledge on risk factors, symptoms and intended behavior of women and men towards screening and treatment of cervical cancer in rural Uganda: a cross-sectional study.

BACKGROUND: Knowledge of risk factors and symptoms of cervical cancer has been found to promote uptake of screening of cervical cancer. Most interventions targeted women without much involvement of men (husbands/decision makers) who are often decision makers in many low- and middle-income countries. This study aimed at assessing baseline knowledge and intended behavior of both women and men to enable design specific targeted messages to increase uptake of cervical cancer screening and promote early detection of women with symptoms. METHODS: This cross-sectional study was conducted in two districts in Western Uganda using the modified African Women Awareness of CANcer (AWACAN) questionnaire. Women aged 30-49 years and their husbands/decision makers were interviewed. Knowledge on risk factors and symptoms, intended behavior and barriers towards participation in cervical cancer screening and treatment were assessed. Descriptive and logistic regression analyses were done to establish the association between knowledge levels and other factors comparing women to men. RESULTS: A total of 724 women and 692 men were enrolled. Of these, 71.0% women and 67.2% men had ever heard of cervical cancer and 8.8% women had ever been screened. Knowledge of risk factors and symptoms of cervical cancer was high and similar for both women and men. Lack of decision making by women was associated with low knowledge of risk factors (X2 = 14.542; p = 0.01), low education (X2 = 36.05, p < 0.01) and older age (X2 = 17.33, p < 0.01). Men had better help seeking behavior than women (X2 = 64.96, p < 0.01, OR = 0.39, 95% CI: 0.31-0.50) and were more confident and skilled in recognising a sign or symptom of cervical cancer (X2 = 27.28, p < 0.01, OR = 0.52, CI (0.40-0.67). CONCLUSION: The baseline knowledge for cervical cancer was high in majority of participants and similar in both women and men. Their intended behavior towards screening was also positive but screening uptake was very low. This study suggests developing messages on multiple interventions to promote screening behavior in addition to education, consisting of male involvement, women empowerment and making services available, accessible and women friendly.

Surgical candidacy and treatment initiation among women with cervical cancer at public referral hospitals in Kampala, Uganda: a descriptive cohort study.

OBJECTIVES: This study aimed to report the proportion of women with a new diagnosis of cervical cancer recommended for curative hysterectomy as well as associated factors. We also report recommended treatments by stage and patterns of treatment initiation. DESIGN: This was an observational cohort study. Inperson surveys were followed by a phone call. SETTING: Participants were recruited at the two public tertiary care referral hospitals in Kampala, Uganda. PARTICIPANTS: Adult women with a new diagnosis of cervical cancer were eligible: 332 were invited to participate, 268 met the criteria and enrolled, and 255 completed both surveys. PRIMARY AND SECONDARY OUTCOMES MEASURES: The primary outcome of interest was surgical candidacy; a secondary outcome was treatment initiation. Descriptive and multivariate statistical analyses examined the associations between predictors and outcomes. Sensitivity analyses were performed to examine outcomes in subgroups, including stage and availability of radiation. RESULTS: Among 268 participants, 76% were diagnosed at an advanced stage (IIB-IVB). In total, 12% were recommended for hysterectomy. In adjusted analysis, living within 15 km of Kampala (OR 3.10, 95% CI 1.20 to 8.03) and prior screening (OR 2.89, 95% CI 1.22 to 6.83) were significantly associated with surgical candidacy. Radiotherapy availability was not significantly associated with treatment recommendations for early-stage disease (IA-IIA), but was associated with recommended treatment modality (chemoradiation vs primary chemotherapy) for locally advanced stage (IIB-IIIB). Most (67%) had started treatment. No demographic or health factor, treatment recommendation, or radiation availability was associated with treatment initiation. Among those recommended for hysterectomy, 55% underwent surgery. Among those who had initiated treatment, 82% started the modality that was recommended. CONCLUSION: Women presented to public referral centres in Kampala with mostly advanced-stage cervical cancer and few were recommended for surgery. Most were able to initiate treatment. Lack of access to radiation did not significantly increase the proportion of early-stage cancers recommended for hysterectomy.

Piperaquine Exposure Is Altered by Pregnancy, HIV, and Nutritional Status in Ugandan Women.

Dihydroartemisinin-piperaquine (DHA-PQ) provides highly effective therapy and chemoprevention for malaria in pregnant African women. PQ concentrations of >10.3 ng/ml have been associated with reduced maternal parasitemia, placental malaria, and improved birth outcomes. We characterized the population pharmacokinetics (PK) of PQ in a post hoc analysis of human immunodeficiency virus (HIV)-infected and -uninfected pregnant women receiving DHA-PQ as chemoprevention every 4 or 8 weeks. The effects of covariates such as pregnancy, nutritional status (body mass index [BMI]), and efavirenz (EFV)-based antiretroviral therapy were investigated. PQ concentrations from two chemoprevention trials were pooled to create a population PK database from 274 women and 2,218 PK observations. A three-compartment model with an absorption lag best fit the data. Consistent with our prior intensive PK evaluation, pregnancy and EFV use resulted in a 72% and 61% increased PQ clearance, compared to postpartum and HIV-uninfected pregnant women, respectively. Low BMI at 28 weeks of gestation was associated with increased clearance (2% increase per unit decrease in BMI). Low-BMI women given DHA-PQ every 8 weeks had a higher prevalence of parasitemia, malaria infection, and placental malaria compared to women with higher BMIs. The reduced piperaquine exposure in women with low BMI as well as during EFV coadministration, compared to pregnant women with higher BMIs and not taking EFV, suggests that these populations could benefit from weekly instead of monthly dosing for prevention of malaria parasitemia. Simulations indicated that because of the BMI-clearance relationship, weight-based regimens would not improve protection compared to a 2,880 mg fixed-dose regimen when provided monthly. (The clinical trials described in this paper have been registered at ClinicalTrials.gov under identifiers NCT02163447 and NCT02282293.).

A public health approach to cervical cancer screening in Africa through community-based self-administered HPV testing and mobile treatment provision.

The World Health Organization (WHO) refers to cervical cancer as a public health problem, and sub-Saharan Africa bears the world's highest incidence. In the realm of screening, simplified WHO recommendations for low-resource countries now present an opportunity for a public health approach to this public health problem. We evaluated the feasibility of such a public health approach to cervical cancer screening that features community-based self-administered HPV testing and mobile treatment provision. In two rural districts of western-central Uganda, Village Health Team members led community mobilization for cervical cancer screening fairs in their communities, which offered self-collection of vaginal samples for high-risk human papillomavirus (hrHPV) testing. High-risk human papillomavirus-positive women were re-contacted and referred for treatment with cryotherapy by a mobile treatment unit in their community. We also determined penetrance of the mobilization campaign message by interviewing a probability sample of adult women in study communities about the fair and their attendance. In 16 communities, 2142 women attended the health fairs; 1902 were eligible for cervical cancer screening of which 1892 (99.5%) provided a self-collected vaginal sample. Among the 393 (21%) women with detectable hrHPV, 89% were successfully contacted about their results, of which 86% returned for treatment by a mobile treatment team. Most of the women in the community (93%) reported hearing about the fair, and among those who had heard of the fair, 68% attended. This public health approach to cervical cancer screening was feasible, effectively penetrated the communities, and was readily accepted by community women. The findings support further optimization and evaluation of this approach as a means of scaling up cervical cancer control in low-resource settings.

Prevalence, correlates, and predictive value of high-risk human papillomavirus mRNA detection in a community-based cervical cancer screening program in western Uganda.

BACKGROUND: New strategies are needed to combat the high incidence of cervical cancer in resource-limited settings such as sub-Saharan Africa. Screening for high-risk human papillomavirus (hrHPV) DNA is sensitive for pre-cancer, but its lack of specificity results in substantial overtreatment in low resource settings where additional testing (e.g., colposcopy) is rarely available. Testing for hrHPV E6/E7 mRNA may enhance specificity, but little is known about its performance characteristics in resource-limited settings. METHODS: In a series of community health fairs in rural Uganda, women aged 25 to 49 years provided self-collected vaginal samples, which were tested for hrHPV (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68) E6/E7 mRNA with the Aptima® assay. Positive specimens underwent testing for HPV-16 and 18/45. After excluding pregnant women, all women testing positive for any hrHPV subsequently were offered cervical biopsy to determine pathology. RESULTS: A total of 1892 women provided a vaginal sample for hrHPV testing during 24 health fairs. The median age was 34 years, HIV prevalence was 10, and 95% had not been previously screened. Prevalence of any hrHPV E6/E7 mRNA was 21% (95% confidence interval (CI): 19 to 23%); the prevalence of HPV-16 was 2.6%, HPV-18/45 1.9%, and HPV 16 and 18/45 were jointly found in 0.1% of the study population. Younger age, pregnancy and HIV-positivity were independently associated with any hrHPV infection. Of the 255 evaluable cervical biopsies, the positive predictive value of detecting any hrHPV E6/E7 mRNA for presence of cervical intraepithelial neoplasia grade 2 or higher ("CIN 2+") was 8.2% (95% CI: 5.1 to 12%). The positive predictive value associated with detection of HPV-16 mRNA (15%) or HPV-18/45 mRNA (15%) was only slightly higher. CONCLUSION: Among community-based women in Uganda, the prevalence of any hrHPV E6/E7 mRNA in vaginal samples was high, but the prevalence of the most oncogenic HPV types (16, 18, or 45) was substantially lower. Positive predictive value of hrHPV mRNA-positivity for CIN 2+ was also low, including when restricting to HPV 16/18/45-positivity. The findings emphasize the need to identify more specific screening approaches for cervical cancer.

Dihydroartemisinin-piperaquine for intermittent preventive treatment of malaria during pregnancy and risk of malaria in early childhood: A randomized controlled trial.

BACKGROUND: Intermittent preventive treatment of malaria in pregnancy (IPTp) with dihydroartemisinin-piperaquine (IPTp-DP) has been shown to reduce the burden of malaria during pregnancy compared to sulfadoxine-pyrimethamine (IPTp-SP). However, limited data exist on how IPTp regimens impact malaria risk during infancy. We conducted a double-blinded randomized controlled trial (RCT) to test the hypothesis that children born to mothers given IPTp-DP would have a lower incidence of malaria during infancy compared to children born to mothers who received IPTp-SP. METHODS AND FINDINGS: We compared malaria metrics among children in Tororo, Uganda, born to women randomized to IPTp-SP given every 8 weeks (SP8w, n = 100), IPTp-DP every 8 weeks (DP8w, n = 44), or IPTp-DP every 4 weeks (DP4w, n = 47). After birth, children were given chemoprevention with DP every 12 weeks from 8 weeks to 2 years of age. The primary outcome was incidence of malaria during the first 2 years of life. Secondary outcomes included time to malaria from birth and time to parasitemia following each dose of DP given during infancy. Results are reported after adjustment for clustering (twin gestation) and potential confounders (maternal age, gravidity, and maternal parasitemia status at enrolment).The study took place between June 2014 and May 2017. Compared to children whose mothers were randomized to IPTp-SP8w (0.24 episodes per person year [PPY]), the incidence of malaria was higher in children born to mothers who received IPTp-DP4w (0.42 episodes PPY, adjusted incidence rate ratio [aIRR] 1.92; 95% CI 1.00-3.65, p = 0.049) and nonsignificantly higher in children born to mothers who received IPT-DP8w (0.30 episodes PPY, aIRR 1.44; 95% CI 0.68-3.05, p = 0.34). However, these associations were modified by infant sex. Female children whose mothers were randomized to IPTp-DP4w had an apparently 4-fold higher incidence of malaria compared to female children whose mothers were randomized to IPTp-SP8w (0.65 versus 0.20 episodes PPY, aIRR 4.39, 95% CI 1.87-10.3, p = 0.001), but no significant association was observed in male children (0.20 versus 0.28 episodes PPY, aIRR 0.66, 95% CI 0.25-1.75, p = 0.42). Nonsignificant increases in malaria incidence were observed among female, but not male, children born to mothers who received DP8w versus SP8w. In exploratory analyses, levels of malaria-specific antibodies in cord blood were similar between IPTp groups and sex. However, female children whose mothers were randomized to IPTp-DP4w had lower mean piperaquine (PQ) levels during infancy compared to female children whose mothers received IPTp-SP8w (coef 0.81, 95% CI 0.65-1.00, p = 0.048) and male children whose mothers received IPTp-DP4w (coef 0.72, 95% CI 0.57-0.91, p = 0.006). There were no significant sex-specific differences in PQ levels among children whose mothers were randomized to IPTp-SP8w or IPTp-DP8w. The main limitations were small sample size and childhood provision of DP every 12 weeks in infancy. CONCLUSIONS: Contrary to our hypothesis, preventing malaria in pregnancy with IPTp-DP in the context of chemoprevention with DP during infancy does not lead to a reduced incidence of malaria in childhood; in this setting, it may be associated with an increased incidence of malaria in females. Future studies are needed to better understand the biological mechanisms of in utero drug exposure on drug metabolism and how this may affect the dosing of antimalarial drugs for treatment and prevention during infancy. TRIAL REGISTRATION: ClinicalTrials.gov number NCT02163447.

Acceptability of study procedures (self-collected introital swabs, blood draws and stool sample collection) by students 10-16 years for an HPV vaccine effectiveness study: a pilot study.

BACKGROUND: A cohort study was planned to evaluate vaccine immunogenicity and effect of malaria and helminth co-infections on the bivalent Human papilloma virus (HPV) vaccine. The study would involve self collected introital swabs, blood draws and stool sample collection. We therefore conducted a pilot study to assess the acceptability of these procedures among the students and their parents. RESULTS: A cross-sectional study among forty four students from two purposively selected primary schools of Western Uganda. Exit interviews and two focus group discussions (FGD) (for parents) were conducted. Acceptability was measured by willingness to undergo the procedures again, recommending the procedures to others as well as proportion of introital swabs positive for ß globulin. FGD determined acceptability of the parents and explored opinions and perceptions that would influence their decisions. HPV-16/18 and ß globulin deoxyribonucleic acid (DNA) were analysed using a polymerase chain reaction (PCR) kit. All the students (100%) in the study were willing to provide a self- collected introital swab and a stool sample as well as recommending their friends while (86.3%) were willing for blood draws. There were 40/44 (90.1%) self collected introital swabs that had positive result for human ß globulin though none of them was positive for HPV-16/18. In the FGD, it emerged that parents concerns were on the blood draws and introital swab collection which were addressed. CONCLUSIONS: The study procedures were highly acceptable among this study population of students and their parents. Follow-up to assess HPV vaccine effectiveness and factors that may influence the vaccine in this age group is feasible.

The time has come to make cervical cancer prevention an essential part of comprehensive sexual and reproductive health services for HIV-positive women in low-income countries.

INTRODUCTION: HIV and cervical cancer are intersecting epidemics that disproportionately affect one of the most vulnerable populations in the world: women in low- and middle-income countries (LMICs). Historically, the disparity in cervical cancer risk for women in LMICs has been due to the lack of organized screening and prevention programmes. In recent years, this risk has been augmented by the severity of the HIV epidemic in LMICs. HIV-positive women are at increased risk for developing cervical precancer and cancer, and while the introduction of antiretroviral therapy has dramatically improved life expectancies among HIV-positive women it has not been shown to improve cancer-related outcomes. Therefore, an increasing number of HIV-positive women are living in LMICs with limited or no access to cervical cancer screening programmes. In this commentary, we describe the gaps in cervical cancer prevention, the state of evidence for integrating cervical cancer prevention into HIV programmes and future directions for programme implementation and research. DISCUSSION: Despite the biologic, behavioural and demographic overlap between HIV and cervical cancer, cervical cancer prevention has for the most part been left out of sexual and reproductive health (SRH) services for HIV-positive women. Lower cost primary and secondary prevention strategies for cervical cancer are becoming more widely available in LMICs, with increasing evidence for their efficacy and cost-effectiveness. Going forward, cervical cancer prevention must be considered a part of the essential package of SRH services for HIV-positive women. Effective cervical cancer prevention programmes will require a coordinated response from international policymakers and funders, national governments and community leaders. Leveraging the improvements in healthcare infrastructure created by the response to the global HIV epidemic through integration of services may be an effective way to make an impact to prevent cervical cancer among HIV-positive women, but more work remains to determine optimal approaches. CONCLUSIONS: Cervical cancer prevention is an essential part of comprehensive HIV care. In order to ensure maximal impact and cost-effectiveness, implementation strategies for screening programmes must be adapted and rigorously evaluated through a framework that includes equal participation with policymakers, programme planners and key stakeholders in the target communities.

Vaccines against human papillomavirus in low and middle income countries: a review of safety, immunogenicity and efficacy.

Currently, there is limited data on the immunogenicity and efficacy of human papillomavirus vaccines in Low and Middle income countries (LMIC). The review aims to summarize the current status from published HPV vaccine safety, immunogenicity and efficacy studies in low and middle income countries (LMIC). Electronic databases (PubMed/MEDLINE and HINARI) were searched for peer reviewed English language articles on HPV vaccination in LMIC that have so far been published from 1st January 2006 up to 30th January 2015. Eligible studies were included if they had used the bivalent (bHPV) or quadrivalent HPV (qHPV) vaccines in a LMIC and investigated safety, immunogenicity and/or efficacy. The main findings were extracted and summarized. A total of fourteen HPV vaccine studies assessing safety, Immunogenicity and efficacy of the bivalent or quadrivalent vaccines in LMIC were included. There are only ten published clinical trials where a LMIC has participated. There was no published study so far that assessed efficacy of the HPV vaccines in Sub-Saharan Africa. From these studies, vaccine induced immune response was comparable to that from results of HICs for all age groups. Studies assessing HPV vaccine efficacy of the bivalent or quadrivalent vaccine within LMIC were largely missing. Only three studies were found where a LMIC was part of a multi center clinical trial. In all the studies, there were no vaccine related serious adverse events. The findings from the only study that investigated less than three doses of the bivalent HPV-16/18 vaccine suggest that even with less than three doses, antibody levels were still comparable with older women where efficacy has been proven. The few studies from LMIC in this review had comparable safety, Immunogenicity and efficacy profiles like in HIC. Overall, the LMIC of Africa where immune compromising/modulating situations are prevalent, there is need for long term immunogenicity as well as surveillance studies for long term clinical effectiveness after two and three dose regimens.

Immunogenicity to the bivalent HPV-16/18 vaccine among adolescent African students exposed to helminths and malaria.

INTRODUCTION: Efficacious vaccines that prevent human papillomavirus (HPV) infection, the recognized cause of cervical cancer, are now available. However, in sub-Saharan Africa, immune-modulating infections such as helminths and malaria may affect immunogenicity to the HPV vaccine. This study aimed to evaluate the effect of helminth infections and exposure to malaria on the immune response to the bivalent HPV-16/18 vaccine. METHODOLOGY: AS04-adjuvanted HPV-16/18 vaccinated students between 10 and 16 years of age from western Uganda, at 18 months-post vaccination were followed up for six months. After consent was obtained, demographic data, blood, and stool samples were collected. Multiplex HPV serology technology was used to determine HPV-16/18 antibody levels expressed as median fluorescent intensity (MFI). The malaria antibody immunoassay test was used to detect antibodies to malaria parasites. The Kato-Katz method was used to detect the presence of helminths. HPV-16/18 antibody levels among students exposed to malaria or helminths were compared with those who were not exposed using the Student's t-test. RESULTS: A total of 211 students participated in the study. There was no difference between MFI levels to HPV-16/18 antibodies at 18- and 24-month follow-ups among students who were positive and negative to malaria or helminth exposure. There was an increase in HPV-18 MFI antibody levels at month 24 among the students who were positive for malaria at enrolment (p = 0.05). CONCLUSIONS: Immune-modulating parasites (malaria/helminths) were not associated with reduced immune response to the bivalent HPV-16/18 vaccine. The data may support the use of this vaccine in sub-Saharan Africa.

The levels of anti-HPV16/18 and anti-HPV31/33/35/45/52/58 antibodies among AS04-adjuvanted HPV16/18 vaccinated and non-vaccinated Ugandan girls aged 10-16 years.

BACKGROUND: Data on Human Papilloma virus (HPV) vaccine immune response in sub-Saharan Africa is still sparse yet such knowledge is critical for optimal implementation and monitoring of HPV vaccines. Our primary objective was to evaluate levels of anti-HPV-16/18 antibodies and six other 'high risk' HPV (hrHPV) types among the vaccinated and unvaccinated Ugandan girls. METHODS: We conducted a cross sectional study among AS04-adjuvanted HPV-16/18 vaccinated and unvaccinated school girls aged 10-16 years in Western Uganda using purposive sampling. The vaccinated girls were at 18 months post vaccination. After consenting and assenting, data was collected using interviewer administered questionnaires for demographics and sexual history. Blood was drawn from which serum samples were analysed by the multiplex HPV serology technology to determine anti-HPV antibody levels to HPV-16/18 and six other hrHPV types (31, 33, 35, 45, 52 and 58). The antibody levels were expressed as Median Fluorescent Intensity (MFI). A total of 207 vaccinated [mean age 13.1 years (SD 1.5); range 10-16 years] and 197 unvaccinated girls [mean age 13.6 years (SD 1.3); range 10-16 years] participated in the study. Sexual activity was self reported among 14/207 (6.8%) vaccinated and 5/197 (2.5%) unvaccinated girls. The MFI levels for HPV-16 and HPV-18 were 15 and 20 times higher respectively in the vaccinated girls than in the unvaccinated girls. HPV-16 mean MFI level was 4691(SD 1812; 95% CI: 4438-4958) among the vaccinated compared to 218 (SD 685; 95% CI: 190-252) among the unvaccinated girls. For HPV-18 the mean MFI level was 1615 (SD 1326; 95% CI: 1470-1776) among the vaccinated compared to MFI 103 (SD 506; 95% CI: 88 -121) among unvaccinated girls. In addition antibody levels to non vaccine hrHPV types (31, 33, 35, 45, 52 and 58) were all significantly higher in the vaccinated group than in the unvaccinated group (p<0.01). CONCLUSION: The AS04-Adjuvanted HPV-16/18 vaccinated girls showed a higher level of antibodies to HPV-16/18 and other non-vaccine hrHPV types compared to the unvaccinated girls. This may translate into protection against HPV-16/18 and other hrHPV types.