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.BioMed Central open acces

Low avidity of human papillomavirus (HPV) type 16 antibodies is associated with increased risk of low-risk but not high-risk HPV type prevalence

Background Low avidity of antibodies against viral, bacterial and parasitic agents has been used for differential diagnosis of acute versus recent/past infections. The low-avidity antibodies may however, persist for a longer period in some individuals. Findings We studied the association of human papillomavirus (HPV) type 16 antibody avidity with seroprevalence to HPV types 6/11/18/31/33/45. Antibody avidity was analysed for 365 HPV16 seropositive pregnant Finnish and Ugandan women using a modified ELISA. Low avidity of HPV16 antibodies was found in 15% of Finnish and 26% of Ugandan women. Ugandan women with low-avidity HPV16 antibodies had an increased risk estimate for HPV6/11 (odds ratio, OR 2.9; 95%CI 1.01-8.4) seropositivity but not to high-risk HPV types 18/31/33/45. Conclusion Association of the low avidity HPV16 antibody "phenotype" with possible susceptibility to infections with other HPV types warrants investigation.BioMed Central Open acces

Type-specific incidence, clearance and predictors of cervical human papillomavirus infections (HPV) among young women: a prospective study in Uganda

<p>Abstract</p> <p>Background</p> <p>While infections with human papillomavirus (HPV) are highly prevalent among sexually active young women in Uganda, information on incidence, clearance and their associated risk factors is sparse. To estimate the incidence, prevalence and determinants of HPV infections, we conducted a prospective follow-up study among 1,275 women aged 12-24 years at the time of recruitment. Women answered a questionnaire and underwent a pelvic examination at each visit to collect exfoliated cervical cells. The presence of 42 HPV types was evaluated in exfoliated cervical cells by a polymerase chain based (PCR) assay (SPF10-DEIA LiPA).</p> <p>Results</p> <p>Three hundred and eighty (380) of 1,275 (29.8%) women were followed up for a median time of 18.5 months (inter-quartile range 9.7-26.6). Sixty-nine (69) women had incident HPV infections during 226 person-years of follow-up reflecting an incidence rate of 30.5 per 100 person-years. Incident HPV infections were marginally associated with HIV positivity (RR = 2.8, 95% CI: 0.9 - 8.3). Clearance for HPV type-specific infections was frequent ranging between 42.3% and 100.0% for high- and 50% and 100% for low-risk types. Only 31.2% of women cleared all their infections. Clearance was associated with HIV negativity (Adjusted clearance = 0.2, 95% CI: 0.1 - 0.7) but not with age at study entry, lifetime number of sexual partners and multiplicity of infections. The prevalence of low-grade squamous intraepithelial lesions (LSILs) was 53/365 (14.5%). None of the women had a high-grade cervical lesion (HSIL) or cancer. Twenty-two (22) of 150 (14.7%) HPV negative women at baseline developed incident LSIL during follow-up. The risk for LSIL appeared to be elevated among women with HPV 18-related types compared to women not infected with those types (RR = 3.5, 95% CI: 1.0 - 11.8).</p> <p>Conclusions</p> <p>Incident HPV infections and type-specific HPV clearance were frequent among our study population of young women. These results underscore the need to vaccinate pre-adolescent girls before initiation of sexual activity.</p

The Burden of Human Papillomavirus Infections and Related Diseases in Sub-Saharan Africa

Despite the scarcity of high quality cancer registries and lack of reliable mortality data, it is clear that human papillomavirus (HPV)-associated diseases, particularly cervical cancer, are major causes of morbidity and mortality in sub-Saharan Africa (SSA). Cervical cancer incidence rates in SSA are the highest in the world and the disease is the most common cause of cancer death among women in the region. The high incidence of cervical cancer is a consequence of the inability of most countries to either initiate or sustain cervical cancer prevention services. In addition, it appears that the prevalence of HPV in women with normal cytology is higher than in more developed areas of the world, at an average of 24%. There is, however, significant regional variation in SSA, with the highest incidence of HPV infection and cervical cancer found in Eastern and Western Africa. It is expected that, due to aging and growth of the population, but also to lack of access to appropriate prevention services and the concomitant human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) epidemic, cervical cancer incidence and mortality rates in SSA will rise over the next 20 years. HPV16 and 18 are the most common genotypes in cervical cancer in SSA, although other carcinogenic HPV types, such as HPV45 and 35, are also relatively more frequent compared with other world regions. Data on other HPV-related anogenital cancers including those of the vulva, vagina, anus, and penis, are limited. Genital warts are common and associated with HPV types 6 and 11. HIV infection increases incidence and prevalence of all HPV-associated diseases. Sociocultural determinants of HPV-related disease, as well as the impact of forces that result in social destabilization, demand further study. Strategies to reduce the excessive burden of HPV-related diseases in SSA include age-appropriate prophylactic HPV vaccination, cervical cancer prevention services for women of the reproductive ages, and control of HIV/AIDS

Low avidity of human papillomavirus (HPV) type 16 antibodies is associated with increased risk of low-risk but not high-risk HPV type prevalence

Peer reviewe

Epidemiology of HPV genotypes in Uganda and the role of the current preventive vaccines: A systematic review

<p>Abstract</p> <p>Background</p> <p>Limited data are available on the distribution of human papillomavirus (HPV) genotypes in the general population and in invasive cervical cancer (ICC) in Uganda. Yet, with the advent of preventive HPV vaccines that target HPV 16 and 18 responsible for causing about 70% of ICC cases in the world, such information is crucial to predict how vaccination and HPV-based screening will influence prevention of ICC.</p> <p>Methods</p> <p>To review the distribution of HPV infection and prevalent genotypes, electronic databases (e.g. PubMed/MEDLINE and HINARI) were searched for peer reviewed English articles on HPV infection up to November 30, 2010. Eligible studies were selected according to the following criteria: DNA-confirmed cervical or male genital HPV prevalence and genotypes, HPV incidence estimates and HPV seroprevalence among participants.</p> <p>Results</p> <p>Twenty studies were included in the review. Among HIV negative adult women, the prevalence of HR-HPV infections ranged from 10.2% -40.0% compared to 37.0% -100.0% among HIV positive women. Among HIV positive young women aged below 25 years, the prevalence of HR-HPV genotypes ranged from 41.6% -75.0% compared to 23.7% -67.1% among HIV negative women. Multiple infections with non vaccine HR-HPV genotypes were frequent in both HIV positive and HIV negative women. The main risk factors for prevalent HPV infections were age, lifetime number of sexual partners and HIV infection. Incident infections with HR-HPV genotypes were more frequent among adult HIV positive than HIV negative women estimated at 17.3 and 7.0 per 100 person-years, respectively. Similarly, incident HR-HPV among young women aged below 25 years were more frequent among HIV positive (40.0 per 100 person-years) than HIV negative women (20.3 per 100 person-years) women. The main risk factor for incident infection was HIV infection. HPV 16 and 18 were the most common genotypes in ICC with HPV 16/18 contributing up to 73.5% of cases with single infections.</p> <p>Among uncircumcised adult HIV positive males, HR-HPV prevalence ranged from 55.3% -76.6% compared to 38.6% -47.6% in HIV negative males. Incident and multiple HR-HPV infections were frequent in HIV positive males. Being uncircumcised was the main risk factor for both prevalent and incident HPV infection.</p> <p>Conclusion</p> <p>Infections with HR-HPV genotypes were very common particularly among HIV positive individuals and young women irrespective of HIV status. Given the high prevalence of HIV infection, HPV-associated conditions represent a major public health burden in Uganda. However, although the most common HPV genotypes in ICC cases in Uganda were those targeted by current preventive vaccines, there were a large number of individuals infected with other HR-HPV genotypes. Technology allowing, these other HR-HPV types should be considered in the development of the next generation of vaccines.</p

Human papillomavirus infections among sexually active young women in Uganda : Implications for a vaccination strategy

Introduction: Information about the genital (human papillomavirus) HPV infection is needed to support the introduction of HPV vaccination in Uganda. Objectives: (i) To estimate the prevalence, incidence, clearance and to evaluate the associated risk factors for the genital HPV infection. (ii) To evaluate in a pilot study the possibility of using filter paper to collect, store and transport cervical material for HPV DNA testing and genotyping. Subjects and Methods: We conducted two clinic-based prospective cohort studies between September 2002 and December 2006. We consecutively recruited 1,275 sexually active women among those seeking services at Naguru Teenage Information and Health Centre (NTIHC) and 1,097 consecutive young primigravidae from those seeking pre-natal care at Naguru Health Centre (NHC) in Kampala, Uganda. Women were followed up for an average of 18.5 months (range 9.7-26.6). Detailed information on socio-demographic characteristics, reproductive and menstrual factors, sexual behaviour, history of sexually transmitted diseases of the women and their sexual partner(s), use of contraceptive methods and other lifestyle characteristics was obtained at baseline and follow up using interviewer administered standardized questionnaires. Cervical exfoliated cells were collected in Phosphate Buffer Saline (PBS) or PreservCyt solution as well as on filter paper. A sensitive PCR assay (SPF10/LiPA) was used to detect 42 different genital HPV types. Results: In Paper I, only 32.4% of HPV types determined with filter paper were verifiable with PBS (kappa statistic = 0.18). Multiple HPV types were detected in 54.1% of PBS compared to 15.3% of filter paper samples. Infections with ¡Ý 4 HPV types were 18.0% in PBS compared to2.7% in filter paper samples. In Paper II, the prevalence of HPV and HIV infections was 74.6% and 8.6%, respectively. High-risk HPV (HR-HPV) types were found in 51.4% of the women. The most frequently detected HR-HPV types were 51, 52, 18 and 16. Multiple infections were frequent. HIV positive women had a higher HPV prevalence (87.8%) and multiple infections (64.6%) than HIV negative women, 73.2% and 37.3%, respectively. Employment in the tertiary sector, lifetime number of sexual partners, a positive pregnancy test and detection of genital warts were significantly associated with HPV positivity. In Paper III, the incidence rate of HPV infections was 30.5 per 100 person-years. The risk for incident infections was not statistically significant among HIV positive compared to HIV negative women (Risk Ratio, [RR] = 2.8, 95%; 95% Confidence Interval [CI]; 0.9-8.3). Clearance for the individual HPV type was frequent; 42.3-100.0 % for HR-HPV types and 50-100% for low-risk types. HIV negative women cleared their infection more frequently than HIV positive women (clearance Adjusted = 0.2, 95% CI = 0.1-0.7). In Paper IV, the prevalence of HPV infections was 60% among young primigravidae. HPV 16 and 18 were detected in 8.4% and 5.8%, respectively, which was less frequent than HPV 51 (8.7%) and HPV 52 (12.1%). Although HPV infections were detected in 42.9% of women between the 1st/2nd and 3rd trimesters, and 38.1% between pregnancy and delivery, 50.0% and 71.8% of HPV infections, respectively cleared, leaving the HPV prevalenceunchanged in different periods of pregnancy. Conclusion: The prevalence and incidence of high-risk HPV infections were extremely high in our study populations of young women in Kampala, Uganda. Clearance of HPV infections was frequent but had no effect on prevalence