Objectives: The aims of this study were to: 1) Assess whether naturally induced anti-HPV antibodies are associated with subsequent acquisition of genital HPV 6, 11, 16, and 18 infections in men, 2) assess the recurrence (redetection) of genital HPV infections of the 9-valent vaccine HPV types and investigate factors associated with recurrent infections among men, and 3) assess the risk of type-specific sequential acquisition of anal HPV infection following a genital HPV infection of the 9-valent vaccine HPV types among men who have sex with women (MSW). Methods: 4,123 healthy men were followed every six months (median follow-up time 4.1 years). HPV antibodies were measured at baseline using a virus-like particle-based ELISA assay. Genital and anal HPV genotypes were detected using the Roche Linear Array assays. Kaplan-Meier curves and Cox models were developed to assess associations between serum anti-HPV antibody and subsequent incident HPV infections. Individual type analyses and grouped analyses were carried out to assess type-specific recurrence of the 9-valent vaccine HPV types. Risk of sequential anal HPV infection was assessed by examining incident rate ratios (IRR) and adjusted hazard ratios (aHR) among men with a prior genital HPV infection compared to men without a prior genital HPV infection. Results: 1) Significantly higher rates of incident infections were observed for HPV 16 among baseline HPV 16 seropositive men (aHR 1.37, 95% CI 1.01-1.86). Risk of persistent HPV 18 infection was significantly lower among HPV 18 seropositive men in unadjusted models, but not in the adjusted model, while incident and six-month persistent HPV 6 and 11 infections did not differ by baseline serostatus. 2) Up to 31% of prior prevalent and 20% of prior incident HPV infections recurred over time in individual type analyses. New female sexual partners, frequency of sexual intercourse with female partners, and new male sexual partners were associated with type-specific recurrence of HPV infections (HPV 6, 16, 31 and 58). In grouped analyses, lifetime number of male sexual partners (aOR = 2.40, 95% CI 1.19-4.84) and number of new male sexual partners (aOR 2.35, 95% CI 1.16-4.74) were associated with recurrence of HPV infections. 3) In individual type analyses, men with a prior HPV 16 genital infection had a significantly higher risk of subsequent anal HPV 16 infection (aHR=4.63, 95% CI 1.41-15.23). Significantly higher HRs were observed for any of the nine HPV types (aHR= 2.8, 95% CI1.32-5.99), high risk HPV types (aHR=2.65, 95% CI 1.26, 5.55) and low risk HPV types (aHR=5.89, 95% CI1.29, 27.01) in grouped analyses. Conclusion: Baseline seropositive status among men was not associated with a reduction in subsequent incident genital HPV 6, 11, and 16 infections, but with a possible protective effect for persistent HPV 18 infections. Men are also susceptible to recurrence of type-specific genital HPV infections, and recurrence of HPV infection was associated with high-risk sexual behaviors. MSW men with prior genital HPV infections are more likely to have a subsequent type-specific anal HPV infection than men who did not have prior genital HPV infections. Understanding the natural history of HPV infections among men is essential to control HPV associated diseases in both men and women.

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2016-04-15T12:35:53Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Trabalho e Artigo. BIBLIOTECA.pdf: 1144641 bytes, checksum: 49381fb9cd2af1b7f9dccd4c30011139 (MD5) / Made available in DSpace on 2016-04-15T12:35:53Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Trabalho e Artigo. BIBLIOTECA.pdf: 1144641 bytes, checksum: 49381fb9cd2af1b7f9dccd4c30011139 (MD5) Previous issue date: 2015-09-11 / CAPEs / O câncer de colo uterino é o terceiro câncer mais comum em mulheres. A infecção e persistência do papilomavirus humano (HPV) tem papel fundamental no surgimento e evolução das lesões cervicais, promovendo alterações no ciclo celular e proliferação celular descontrolada através das oncoproteínas E6 e E7. Entretanto, fazem-se necessários diversos outros fatores para o desenvolvimento de neoplasias. Entre estes, encontram-se as metaloproteinases de matriz (MMP), endopeptidases capazes de digerir matriz extracelular, membrana basal e induzir fatores de crescimento, que participam dos processos de invasão, metástase, angiogênese e recidiva tumorais. Em lesões neoplásicas, a síntese de MMPs encontra-se aumentada. Sua atividade normalmente é contrarregulada por inibidores endógenos, sendo muito comum que haja desequilíbrio nesta relação em lesões tumorais. A despeito de muito estudo sobre sua relação com o câncer cervical, sabe-se pouco sobre o papel das MMPs e seus inibidores na progressão de lesões cervicais causadas por HPV. Este estudo procura correlacionar a expressão de TIMP2 e RECK às lesões cervicais causadas por HPV. Foram utilizadas 115 amostras teciduais, obtidas por conização de lesões cervicais uterinas entre 2011 e 2015 no Hospital das Clínicas de Recife, nas quais foi realizado estudo histopatológico e imunohistoquímico. Foi observada reatividade fraca no citoplasma de células do tecido escamoso de 28,5% dos controles, sem nenhuma lâmina demonstrar reatividade moderada ou forte. Quanto ao núcleo, a quase totalidade das amostras não apresentou TIMP-2, enquanto 28,5% dos controles o fez. No epitélio glandular nenhuma amostra do Grupo Controle, NIC I ou NIC II foi positiva para TIMP2 no citoplasma e núcleo. Das amostras de NIC III, 6% demonstraram positividade no citoplasma. Os resultados de RECK no citoplasma do epitélio escamoso mostraram que a expressão de RECK no citoplasma de células epiteliais escamosas é significativamente maior quanto maior o grau de lesão do tecido, exceto no CC, onde a expressão é menor que a das lesões NIC III (p = 0,019). Os resultados demonstraram que a expressão nuclear de RECK em células epiteliais escamosas é significativamente menor nos tecidos displásicos (p < 0,001). Nas análises de citoplasma do epitélio glandular , nenhuma amostra do Grupo Controle, NIC I e NIC II foi positiva, havendo 3,6% de positividade nas lesões de NIC III, todas com reatividade fraca ou moderada, e 10% de positividade moderada nas amostras de CC. Nenhuma das amostras apresentou positividade nuclear. Os resultados obtidos demonstram menor expressão nuclear de TIMP2 e RECK na presença de displasia e maior expressão citoplasmática de RECK nas células escamosas. Esta foi maior quanto mais alto o grau de displasia, mas foi menor nas amostras de carcinoma do que nas de NIC III. Conclui-se que os inibidores de MMPs podem ter utilidade como marcadores imunohistológicos nas lesões cervicais, sendo necessários mais estudos para sua validação prática. / Cervical cancer is the third most common cancer in women. The infection and persistence of human papillomavirus (HPV) plays a key role in the emergence and evolution of cervical lesions, promoting changes in the cell cycle and uncontrolled cell proliferation through the oncoproteins E6 and E7. However, make up several other factors required for the development of malignancies. Among these are the matrix metalloproteinases (MMPs), endopeptidases capable of digesting the extracellular matrix, basement membrane and induce growth factors, that participate in the processes of invasion, metastasis, angiogenesis and tumor recurrence. In neoplastic lesions, MMPs synthesis is increased. Its activity is usually contrarregulada by endogenous inhibitors, being very common there is imbalance in this relationship in tumor lesions. Despite much study on its relationship with cervical cancer, little is known about the role of MMPs and their inhibitors in the progression of cervical lesions caused by HPV. This study tries to correlate the expression of RECK and TIMP2 the cervical lesions caused by HPV. 115 tissue samples were used, obtained by conization to uterine cervical lesions between 2011 and 2015 at the Hospital das Clinicas of Recife, in which was conducted histopathological and immunohistochemical study. Weak reactivity was observed in the cytoplasm of the squamous tissue cells of 28.5% of controls, with no slide show moderate or strong reactivity. As for the core, almost all of the samples showed no TIMP-2, while 28.5% of controls did. Glandular epithelium in any sample of the control group, CIN I or CIN II was positive for TIMP2 in the cytoplasm and nucleus. Samples of CIN III, 6% showed positivity in the cytoplasm. The results of RECK in the cytoplasm of squamous epithelium showed that RECK expression in the cytoplasm of squamous epithelial cells is significantly higher the higher the degree of tissue injury, except DC, where expression is lower than that of CIN III lesions (p = 0.019). The results showed that nuclear RECK expression in squamous epithelial cells is significantly lower in dysplastic tissues (p <0.001). In the cytoplasm analysis of glandular epithelium, no sample of the control group, CIN I and CIN II was positive, with 3.6% of positivity in CIN III lesions, all with low or moderate reactivity, and 10% moderate positivity in the samples DC. None of the samples showed nuclear positivity. The results showed lower nuclear expression TIMP2 and RECK in the presence of dysplasia and increased cytoplasmic expression of RECK in squamous cells. This was greater the higher the degree of dysplasia, but was lower in carcinoma samples than in CIN III. We conclude that MMP inhibitors may have utility as immunohistological markers in cervical lesions, more research is needed to validate your practice.

Les inégalités de participation au dépistage du cancer du col de l’utérus (CCU) sont multifactorielles et la prévention primaire du CCU par la vaccination contre les papillomavirus humains (HPV) oncogènes pourrait présenter des similarités. Médecin de premier recours de l’ensemble de la population, le médecin généraliste (MG) pourrait avoir une place importante dans la limitation de ces inégalités et nous voulions l’explorer avant l’implémentation du dépistage organisé national français (DONF) du CCU.La comparaison des données de remboursement de deux départements français dont l’un participait à l’expérimentation de dépistage organisé, a mis en évidence une participation au dépistage plus importante dans le département d’expérimentation. Le gradient de participation diminuant avec l’augmentation du niveau de défavorisation était plus fort dans le département d’expérimentation, et plus encore en milieu rural. Nos données ne nous ont pas permis d’explorer ces aspects pour la vaccination contre les HPV.Interrogés sur leurs préférences pour limiter ces inégalités dans le cadre du DONF, gynécologues et MG étaient favorables au ciblage des femmes non dépistées, par invitations centralisées impliquant le médecin traitant déclaré ou en leur fournissant la liste des femmes non dépistées de leur patientèle. Le ciblage des femmes de plus de 50 ans ou défavorisées, de même que les autoprélèvements de dépistage des HPV, étaient rejetés par les praticiens.L’ensemble de nos travaux confirmaient l’importance d’un universalisme proportionné lors de l’implémentation du DONF. L’adhésion des praticiens, dont les MG, nécessitera une information sur la motivation des mesures proposées. / Unequal participation in uterine cervical cancer screening (UCC) is multifactorial and primary prevention of UCC by vaccination against oncogenic human papillomavirus (HPV) may have similarities. As primary care physicians for the overall population, general practitioners (GPs) could be a major contributor in limiting these inequalities. We aimed to explore these contributions before the implementation of the French national organized screening (FNOS) of UCC.The comparison of reimbursement data from two French departments, one of which experimented a regional organized screening, revealed a greater participation in screening in the experimental department. The participation gradient decreasing with the increase of deprivation was stronger in the experimental department, and moreover in rural areas. Our data did not allow us to explore these aspects for HPV vaccination.Asked about their preferences to limit these inequalities when implementing the FNOS, gynecologists and GPs were in favour of targeting unscreened women, by centralized invitations involving the declared attending physician, or by providing them with a list of unscreened women among their patients. Targeting women over 50 years old or deprived women, as well as HPV self-sampling, were options rejected by practitioners.Our results confirmed the importance of a proportionate universalism when implementing the FNOS. The involvement of practitioners, including GPs, will require information on the rational of the proposed measures.

The human papillomavirus (HPV) has been a “companion” of humanity for as long as humanity has existed. The migration of peoples around the globe has given rise to more than 170 different types of the virus, which cause a variety of conditions. All five genera of HPV infect epithelial cells in the body, but only the Alphapapillomaviruses infect the genital mucosa. Most infections are benign and typically regress to subclinical within two years, but persistent infections can cause precancerous lesions. HPV types 16 and 18 are among the highest risk and account for the majority of cervical cancer, and more than 90% of all other HPV-related cancers. While the two vaccines, Gardasil and Cervarix, have been successfully implemented in the US market and some European and Asian countries, complete world penetrance has been burdened by multiple factors, including financial constraints and social norms. Treatments for established papillomas are invasive (cryosurgery, conization, etc.) and advanced malignant HPV-related tumors have been targeted with chemo- and radiotherapy with varied success. The high morbidity and long-term effects of current treatment options make clear the need for easy-to-administer, low-cost therapies, which can specifically treat both early and advanced HPV-associated cancers.<div><br></div><div>The hallmark of HPV tumors is the inactivation of p53, an evasion strategy key to the progression of HPV- derived cancers. Through an interaction between the viral protein E6 and the E3 ubiquitin ligase E6AP, p53 is polyubiquitinated and targeted for proteasomal degradation, allowing infected cells to bypass their own defense mechanisms. This work explores interruption of the association between E6 and E6AP as an opportunity to combat the infection and resulting malignancies.<br></div><div><br></div><div>In the first part of this project, disruption of the E6-E6AP interactions is pursued through the development of helical stabilized peptidomimetics of the LxxLL motif, which E6AP uses for E6 recognition and binding. Several reports have indicated that targeting the E6 binding groove is a viable means for disrupting the interaction. However, reported peptides were not cell permeable or optimized for α-helicity and proteolytic resistance (for reference, the LxxLL motif is an α-helix when bound). To address this challenge a peptide stabilization strategy was applied, which uses an all-hydrocarbon chain to connect two non-adjacent residues and enforce α-helicity. Results from in silico simulations and biochemical assay with these new stapled peptides showed that affinity for E6, α-helicity, and cell permeability can all be improved with the installment of the proper staple.<br></div><div><br></div><div>The second question examined by this work is whether fragment-based drug design can be successfully employed to derive new small-molecule inhibitors of the formation of the E6-E6AP complex. From a design perspective, the significant challenge was to define discreet binding hot-spots capable of accommodating fragments with reasonable affinity, which can then be linked together into a complete ligand. Using existing structural knowledge of the E6 protein and computational hot-spot searching tools, three previously-unidentified regions (sub-pockets) on E6 were discovered, which are near but not directly engaged by either the E6AP motif or p53. Using high-throughput in silico and biochemical screening, three sets of sub-pocket specific fragments were defined and elaborated into larger molecules with two different scaffolds. As a result, the work herein presents a stepwise approach to targeting the E6-E6AP protein-protein interaction – the discovery of new binding hot spots, the identification of site-specific fragments, and the design of complete molecules with versatile scaffold.<br></div>

Background: Human papillomavirus (HPV) is one of the most common sexually transmitted infections in the world and there are over 100 different varieties. Several of the varieties can lead to cancer. Although there are vaccines available, the vaccine coverage varies in the providing countries. Aim: The aim of this study was to describe aspects that make guardians choose to refrain from giving their children HPV-vaccines. Method: This Literature study is based on nine qualitative articles published between 2010 and 2020 and the articles were found in Cinahl and PubMed. Results: Guardians who refrained from the HPV-vaccine to their adolescents mentioned varied aspects. Some guardians were concerned about side effects of the vaccine and others mention a lack of knowledge and information about HPV and the vaccine. Guardians expressed concerns about vaccinating against sexually transmitted infections with their adolescents. A varied confidence in health care staff was mentioned by the guardians and they sought information from more unreliable sources such as stories from friends and family or the internet. The fact that HPV-vaccine only was provided to girls, in many of the countries, was a reason for the guardian’s skepticism. Conclusion: The result showed that there are various aspects that make guardians refrain from HPV-vaccine. Some reasons are more common in certain countries. Today's society is multicultural, which leads to a need for more studies to be done from an international perspective. Being able to meet the guardian’s various needs for information about HPV-vaccine is essential to get a higher HPV-vaccine coverage in the world.

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Thesis (PhD)--Stellenbosch University, 2014. / ENGLISH ABSTRACT: Title The Effect of Highly Active Antiretroviral Therapy on Human Papilloma Virus Infection and Cervical Cytological Abnormalities in Women Living With HIV Background Human Papillomavirus (HPV) infection causes cervical cancer. The prevalence of HPV-related dysplastic lesions is significantly higher in patients co-infected with the HI virus and thought to be linked to possible more persistent HPV infection. There is, however, conflicting evidence as to whether treatment of Human Immunodeficiency Virus (HIV) infection with antiretroviral agents may influence cervical HPV infection and the behaviour of Squamous Intraepithelial Lesions (SIL). Aims To examine the effect of the initiation of combination antiretroviral therapy (cART) on: 1) the persistence of cervical Low-grade SIL (LSIL); 2) The progression of cervical LSIL to High-Grade SIL (HSIL); 3) The effectiveness of excision treatment of HSIL 4) HPV genotypes detected, in HIVinfected and uninfected women at the Infectious Diseases Clinic and the Colposcopy Clinic, Tygerberg Teaching Hospital, Cape Town, South Africa. Design and Methods We conducted a retrospective cohort analysis of 1720 women with LSIL of the survival of progression-free-time or time-to-clearance. Time to progression or persistence was compared according to HIV status, antiretroviral treatment and CD4 count. In another retrospective cohort analysis, we investigated the effectiveness of excision treatment in 1848 women who underwent LLETZ or CKC biopsy was used. Logistic regression and survival analysis were used to compare excision treatment failure and recurrence-free time between groups according to HIV status, antiretroviral therapy and CD4 count. To investigate the effect of antiretroviral therapy on the cervical HPV infection, 300 HIV-infected women were prospectively enrolled and followed at 6-monthly interval. Cytological testing and cervical HPV sampling were done at each visit. Biopsy of suspicious lesions and excision treatment were done at colposcopy clinic according to standard a protocol. The Roche Linear array HPV genotyping test was used for HPV detection. Generalized Estimating Equation (GEE) multivariate analysis was applied to investigate the effect of cART on the detection of HPV infection, while adjusting for time-dependent covariates such as CD4 count, sexual activity and excision treatment. The effect on each HPV type was then also compared to the effect on HPV16. Results Overall, we found that there was no difference between the progression of LSIL to HSIL by HIV status. However, among HIV-infected patients, those who started ART before first LSIL had a significantly lower risk for progression (HR 0.66, 95% CI 0.54-0.81). CD4 count did not have an impact on the risk for progression. We also found lower persistence of SIL in the HIV uninfected group (HR 0.69, 95% CI 0.57-0.85) and that cART was independently associated with decreased persistence of LSIL. On the other hand, a higher CD4 count at the time of first LSIL was not associated with lower persistence of the lesion. HIV infected women with HSIL experienced much higher excision treatment failure than uninfected women (53.8% vs. 26.9%, p<0.001). Factors that improved outcome were higher CD4 count and complete excision. cART reduced the risk of detection of any HPV type by 47% (OR 0.53, 95% 0.49-0.58, p<001). When adjusted for covariates, time of exposure to cART and CD4 had a stronger effect. Every month of cART exposure reduced the risk detection of any HPV type with 7%. The effect was also significant on HPV16 alone (OR 0.93, 95% CI 0.90-0.95). All non-oncogenic subtypes were influenced similarly or more strongly than HPV16, as well as oncogenic HPV52. Only one oncogenic subtype HPV subtype, HPV39, was influenced marginally less (ratio of OR 0.95, CI 0.90-0.99, p=0.04). There was an increased risk for any HPV detection at CD4 count<200 (OR 1.63, 95% CI:1.50-1.77), but when adjusted, the time of cART exposure again remained the strongest predictor of risk (OR 0.94, 95% CI:0.93-0.95). Conclusion cART impact the outcome of cervical HPV infection by increasing clearance, decreasing progression of LSIL and recurrence after excision treatment. This effect is time dependent and also associated with CD4 count. Specifically, HPV16 detection risk is also reduced by cART, and all HPV types are influenced at least as much as HPV16, except possibly HPV39. It seems that increased cervical HIVproviral load is associated with HPV detection risk, and both are lowered by cART time. / AFRIKAANSE OPSOMMING: Titel Die Effek van Kombinasie Antiretrovirale Terapie op Menslike Papilloomvirusinfeksie en Servikale Sitologiese Abnormaliteite in Menslike Immuniteitsgebrekvirus-geïnfekteerde Vroue Agtergrond Menslike Papilloomvirusinfeksie (MPV) veroorsaak servikale kanker. Die prevalensie van MPVverwante displastiese letsels is betekenisvol hoër in pasiënte wie ook met Menslike Immuniteitsgebrekvirus (MIV) geïnfekteer is en dit word gereken dat dit te wyte is aan meer persisterende MPV infeksie. Daar is egter teenstrydige bewyse oor of die behandeling van MIV infeksie met antiretrovirale (ART) middels die infeksie met MPV en die gedrag van Plaveisel Intraepiletiële letsels (PIL) kan beïnvloed. Doelwitte Om die effek van die inisiasie van kombinasie ART op: 1) die persistering van Laegraadse PIL (LPIL); 2) die progressie van servikale LPIL na hoëgraadse PIL (HPIL) 3) die sukses van eksisiebehandeling van HPIL; 4) MPV genotypies waarneembaar, in MIV-geïnfekteerde vroue by die Infeksiesiektekliniek en die Kolposkopiekliniek,Tygerberghospitaal, Kaapstad, Suid-Afrika, te ondersoek. Studie-ontwerp en Metodes `n Retrospektiewe kohort-analise op 1720 vroue met LPIL van die oorlewing van progressive-vrye tyd en tyd tot opklaring van PIL is gedoen. Tyd tot progressie of opklaring is vergelyk na aanleiding van die pasiënt se MIV status, behandeling met antiretrovirale terapie en CD4-telling. In nog `n retrospektiewe kohort-analise is die effektiwiteit van eksisiebehandeling in 1848 vroue wie LLETZ or Kouemeskonus eksisie ondergaan het, ondersoek. Logistiese regressie en oorlewingsanalise is toegepas om die voorkoms van onsuksesvolle uitkoms en tyd sonder herhaling van letsels tussen groepe te vergelyk na aanleiding van MIV status, ART en CD4-telling. Om die effek van antiretroviral therapie op servikale MPV infeksie te ondersoek, is 300 MIVgeïnfekteerde vroue opgeneem in `n prospektiewe studie en sesmaandeliks opgevolg. Sitologiese en MPV servikale smere is met elke besoek geneem. Biopsies van verdagte letsels en eksisiebehandeling is by die Kolposkopiekliniek gedoen volgens die standaardpraktyk. Die Roche Linear Array HPV Genotyping toets is gebruik vir MPV deteksie. Algemeen-beraamde vergelyking (GEE) meerveranderlike analise is toegepas om die effek van die anti-MIV terapie op die teenwoordigheid van MPV op die serviks te ondersoek. Die aangepaste effek is ook getoets deur die CD4-telling, die seksuele aktiwiteits- en eksisiebehandelingstatus by elke besoek in ag te neem. Die effek op elke MPV genotipe is laastens dan ook vergelyk met die effek op ‘n spesifieke basislyn genotype; in hierdie geval was MPV16 gekies. Resultate Daar was geen statisties beduidende verskil tussen die progressie van LPIL na HPIL na aanleding van HIV status nie, maar pasiënte wie met ART begin het voordat hulle vir die eerste keer met LPIL gediagnoseer was, het ‘n laer risiko gehad vir progressie (HR 0.66, 95% VI 0.54-0.81). Daar is ook gevind dat dit onafhanklik van die CD4 telling was. Die persistering van PIL was laer in die MIV negatiewe groep (HR 0.69, 95% VI 0.57-0.85), maar ook hier was antiretrovirale behandeling geassosieer met verminderde persistering. Weer eens was daar nie ‘n verband met die CD4 telling nie. MIV-geinfekteerde vroue met HPILwas baie meer geneig tot gefaalde eksisiebehandeling (53.8% teenoor 26.9%, p<0.001). Verbeterde uitkoms was geassosieer met ‘n hoër CD4-telling en ‘n eksisie wat as volledig beskryf was. ART wat reeds voor die eksisiebehandeling begin was, het nie die risiko vir onsuskesvolle uitkoms statisties beduidend verminder nie, maar het egter die risiko vir herhaling van letsels na die eksisie sterk verlaag. ART het die kans dat enige MPV tipe waargeneem sou word, met 47% verlaag (OR 0.53, 95% VI 0.49-0.58, p<001). Wanneer aangepas vir ander faktore, was die tyd wat verloop het sedert ART begin was, sowel as vir die CD4 telling, sterker. Vir elke maand sedert ART begin was, het die kans dat enige MPV tipe waargeneem word, met 7% verminder. `n Soortgelyke effek is op HPV16 alleen gevind (OR 0.93, 95%, VI 0.90-0.95). Die effek was net so sterk of sterker op alle subtipes. Slegs een onkogeniese subtipe, MPV39, was gering minder beïnvloed (ratio van OR 0.95, VI 0.90-0.99, p=0.04). Die kans vir waarneming van enige MPV subtype is hoër wanneer die CD4 telling laer as 200 selle/ɥl is (OR 1.63, 95% VI: 1.50-1.77), maar wanneer aangepas, was die tyd van ART weer eens die sterkste voorspeller van MPV infeksie (OR 0.94, 95% VI:0.93-0.95). Gevolgtrekkings ART verbeter die uitkoms van servikale infeksie met MPV deur progressie en persistering van LPIL en herhaling van PIL na eksisie te verminder. Die effek is tydsafhanklik en word ook deur die CD4 telling beïnvloed. Die kanse dat MPV16 spesifiek waargeneem word, word ook deur ART verminder, en all MPV tipes ondervind dieselfde of groter verlaging van waarnemingsrisiko as MPV16, behalwe miskien MPV39. Ons kon aandui dat verhoogde teenwoordigheid van servikale MIV verband hou met die risiko vir die waarneming van MPV infeksie, en beide word verminer deur die tyd waarmee die pasiënt met ARV terapie behandel is.