Human Papillomavirus Clearance Research Articles

Molecular mechanisms of viral infection and propagation: An overview of the second Advanced Summer School in Africa

Molecular mechanisms of viral infection and propagation: An overview of the second Advanced Summer School in Africa

Spontaneous clearance of high risk human papillomavirus infection

To study the clearance of high risk human papillomavirus (HPV) infection among the women with normal cervical pathologic diagnosis. One hundred and seventy-two HPV-positive cases with normal cervical pathologic diagnosis were enrolled in the study. The infection status of HPV was monitored during follow-up from Aug 2006 to Aug 2008. The time of HPV infection spontaneous clearance, as well as effect factors, were analyzed. During follow-up, there were 62.2% (107 cases, 107/172) of the HPV infection cleared. The medium clearance time was 11.3 months (95%CI: 10.6 - 16.6 months). The medium clearance time of aged < 30 years, 30 - 39 years, 40 - 49 years and > 49 years were 11.3, 12.0, 10.9 and 8.5 months, respectively. There were not significant difference among aged intervals (P = 0.384). The virus copies of HPV-clearance cases and persistent-infection were 22.6 and 95.0, respectively. There was not significant difference between groups (P = 0.061). Most of the high risk HPV infection with normal cervical pathologic diagnosis would spontaneously cleared. Age and HPV copies may play little role in the HPV clearance.

Association Between Serum Cytokine Profiles and Clearance or Persistence of High-Risk Human Papillomavirus Infection: A Prospective Study

The cytokines that may be associated with the clearance or persistence of high-risk human papillomavirus (HPV) infection in patients with mild dysplasia or less of the uterine cervix were determined. A prospective study of 160 patients who harbored high-risk HPV with histologically confirmed mild dysplasia or less between January 2006 and August 2008 was performed. All patients were followed up at every 4 months during the first year. Human papillomavirus DNA tests by the Hybrid Capture 2 method (Digene, Gaithersburg, Md) were performed at every visit on all patients. Blood sampling was performed in all patients at their initial visit, and an enzyme-linked immunosorbent assay was used to measure the serum levels of interferon gamma, tumor necrosis factor alpha, and interleukins 6 and 10. Of the 160 patients, 107 (66.9%) had clearance of HPV infection after 12 months of follow-up. The median age of patients in the persistence group was significantly higher than that of patients in the clearance group (47 vs 38 years, respectively; range, 21-77 vs 21-71 years, respectively; P = 0.0009). In univariate analysis, the number of patients with serum negative for tumor necrosis factor alpha was significantly higher in the clearance group than the persistence group (P = 0.0363). However, in multivariate logistic regression analysis, all 4 cytokines failed to show any significant association with the clearance or persistence of HPV infection. The baseline serum cytokine levels were not associated with the clearance or persistence of HPV infection. Systemic immunity may not influence the natural history of HPV infection.

Genotype-Specific Clearance of Genital Human Papillomavirus (HPV) Infections among Mothers in the Finnish Family HPV Study

The majority of cervical human papillomavirus (HPV) infections in young women are transient, but whether the clearance differs among different HPV genotypes and the different factors predicting genotype-specific clearance are partly unknown. In the Finnish Family HPV Study, 131 of 252 women (mean age, 25.5 years) cleared their infection during the prospective follow-up of 6 years (median, 62.4 months; range, 1.6 to 94.5 months). Cervical scrapings collected at each visit were tested for 24 low-risk and high-risk (HR) HPV types with multiplex HPV genotyping. Poison regression (panel data) was used to estimate predictors for the clearance of species 7 and 9 HPV genotypes. Of all HPV genotypes detected in these women, multiple-type and HPV type 16 (HPV16) infections showed clearance least frequently (46.1% and 50.5%, respectively). The actuarial and crude mean times to first clearance were variable among different genotypes. The actuarial clearance rate (events/person-time at risk) was highest for HPV16 and multiple-type infections, while HPV66 and -82 had the highest crude clearance rate. Independent predictors increasing type-specific clearance of species 7/9 HPV genotypes were older age (incidence rate ratio [IRR] = 1.1; 95% confidence interval [95% CI], 1.03 to 1.18; P = 0.002) and baseline oral HR HPV DNA-negative status (IRR = 2.94; 95% CI, 1.03 to 8.36; P = 0.042), while a higher number of sexual partners during the follow-up decreased the probability of clearance (IIR = 0.35; 95% CI, 0.15 to 0.83; P = 0.018). To conclude, HPV16 and multiple-type infections showed the lowest clearance among young mothers. Increasing age and negative oral HR HPV DNA status at baseline were associated with increased clearance, whereas a higher number of current sexual partners decreased the probability of species 7/9 HPV genotype clearance.

Parametric frailty models for clustered data with arbitrary censoring: application to effect of male circumcision on HPV clearance

BackgroundIn epidemiological studies, subjects are often followed for a period during which study outcomes are measured at selected time points, such as by diagnostic testing performed on biological samples collected at each visit. Although test results may indicate the presence or absence of a disease or condition, they cannot provide information on when exactly it occurred. Such study designs generate arbitrarily censored time-to-event data, which can include left, interval and right censoring. Adding to this complexity, the data may be clustered such that observations within the same cluster are not independent, such as time to recovery of an infectious disease of family or community members. This data structure is observed when evaluating circumcision's effect on clearance of penile high risk human papillomavirus (HR-HPV) infections using data collected from the male circumcision(MC) trial conducted in Rakai, Uganda, where the multiple infections within individual and HPV testings performed at trial follow-up visits gave rise to the clustered data with arbitrary censoring.MethodsWe describe the use of parametric proportional hazards frailty models and accelerated failure time frailty models to examine the relationship between explanatory variables and the survival outcomes that are subject to arbitrary censoring, while accounting for the correlation within clusters. Standard software such as SAS can be used for parameter estimation.ResultsCircumcision's effect on HPV infection was a secondary end point in the Rakai MC trial, and HPV genotyping was conducted for penile samples of a subset of trial participants collected at enrollment, 6, 12 and 24-month follow up visits. At enrollment, 36.7% intervention arm men (immediate circumcision) and 36.6% control arm men (delayed circumcision at 2 years) were infected with HR-HPV, with the number of infections per man being 1-5. The proposed models were used to examine whether MC facilitated clearance of the prevalent infections. Results show that clearance of multiple infections within each man is highly correlated, and clearance was 60% faster if a man was circumcised.ConclusionsParametric frailty models provide viable ways to study the relationship between exposure variables and clustered survival outcome that is subject to arbitrary censoring, as is often observed in HPV epidemiology studies.

Reduced Clearance of Penile Human Papillomavirus Infection in Uncircumcised Men

The relationship between circumcision and the acquisition and clearance of human papillomavirus (HPV) infection was examined in a cohort of 357 men followed up at 2-month intervals for an average of 431 days. There were no differences in HPV acquisition by circumcision status. Clearance of HPV infection, including infection with oncogenic types, was slower in the glans/coronal sulcus of the penis of uncircumcised men than circumcised men. The median duration of HPV infection of the glans/coronal sulcus was significantly longer in uncircumcised men (154 days) than circumcised men (91 days) (P=.04). Circumcision may protect against HPV-associated disease by enhancing the resolution of infection.

Abstract 4714: Oral human papillomavirus infection among HIV infected and uninfected men who have sex with men

Abstract Introduction: Human papillomavirus (HPV) causes a subset of oropharyngeal cancers but the prevalence and risk factors for oral HPV infection are not well understood. Initial studies suggest HIV-infected individuals have an increased incidence of HPV-related cancers including oropharyngeal cancer. Methods: Oral exfoliated cells were collected using a swish and gargle with 10ml of Scope mouthwash in 149 HIV-infected and HIV-uninfected men who have sex with men (MSM) in the Baltimore center of the MACS. Samples were tested for 37 types of HPV DNA using PGMY09/11 consensus primers and line blot hybridization. Logistic regression was used to explore risk factors for infection. Results: Prevalent oral HPV infection was common among the 62 HIV-infected and the 87 HIV-uninfected MSM (39% vs 28%, p=0.15). HPV16 was the most common HPV type detected and was found in an alarming 13% of MSM (8.2% of HIV-infected and 16% of HIV-uninfected MSM, p=0.15). The most common other oncogenic oral HPV infections detected were HPV 66, 68, 83 (2.0% prevalence each), and 45, 53, 58, 59, 73 (1.3% each). In this study 32% of men reported multiple oral sex partners in the past six months. Oral HPV16 prevalence was significantly associated with number of recent oral sexual partners among HIV uninfected (p-trend=0.04) but not HIV infected participants. The majority of HIV-infected participants were currently on HAART (74%), had CD4 cell count&amp;gt;500 (65%) and HIV viral load &amp;lt;500 copies/ml (78%). Oral HPV prevalence was similar among current HAART users (41%) compared to former or never HAART users (27% and 40% respectively) and prevalence increased non-significantly with low CD4 and high HIV viral load. In multivariate analysis of HIV infected but not HIV-uninfected MSM, current marijuana users were over ten times more likely (OR=11.5 95%CI=1.5-17) to have prevalent high risk HPV infection. Conclusions: Oral HPV16 prevalence is high among both HIV uninfected and HIV infected MSM suggesting they may be at increased risk for HPV-associated oropharyngeal cancers. Oral HPV risk factor profiles differed by HIV status. Oral HPV prevalence was similar among HIV infected HAART users and non-users suggesting HAART may not improve oral HPV clearance. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4714.

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

BackgroundWhile 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).ResultsThree 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).ConclusionsIncident 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.

Imiquimod‐induced clearance of HPV is associated with normalization of immune cell counts in usual type vulvar intraepithelial neoplasia

Recently, we reported on the efficacy of imiquimod for treatment of usual type vulvar intraepithelial neoplasia (uVIN). A histologic regression of uVIN to normal tissue was observed in 58% of patients. As success of treatment is related to clearance of high-risk human papilloma virus (HPV), the aim of our study was to assess differences in immune cell counts and in the expression of p16(INK4a) in VIN tissue before and after imiquimod treatment, in relation to HPV clearance and clinical response. Vulvar tissue samples taken prior to imiquimod treatment and 4 weeks after treatment were tested for the presence of HPV. Previously determined immune cell counts (CD1a, CD207, CD208, CD123/CD11c, CD94, CD4, CD8 and CD25/HLA-DR) in epidermis and dermis of 25 VIN patients and 19 healthy controls were completed with the counts for CD14 and CD68. The expression of p16(INK4a) was investigated by immunohistochemistry in 15 patients. Before imiquimod treatment, both HPV cleared and HPV noncleared patients showed mainly in the dermis significantly upregulated immune cell counts compared to healthy controls. However, in patients that cleared HPV and showed histologic regression already 4 weeks after imiquimod treatment, immune cell counts and p16(INK4a) expression were normalized. In conclusion, our data indicate that imiquimod-induced clearance of HPV results in normalization of counts for certain immune cells and is strongly correlated with histologic regression of the disease.

Association of TGF-β1 Genetic Variants with HPV16-positive Oropharyngeal Cancer

Transforming growth factor-beta1 (TGF-beta1) plays an important role in inflammation and immune responses, which control the human papillomavirus (HPV) clearance and escape of immune surveillance, and may contribute to genetic susceptibility to HPV16 infection. In this case series study, we analyzed the HPV16 status in tumor specimens and genotyped three TGF-beta1 polymorphisms using genomic DNA from the blood of 200 squamous cell carcinoma of the oropharynx (SCCOP) cases. We calculated odds ratio (OR) and 95% confidence intervals (95% CI) in univariate and multivariable logistic regression models to examine the association between the TGF-beta1 polymorphisms and HPV16 status in SCCOP. Compared with those with the common homozygous genotype, the TGF-beta1 T869C variant genotypes were significantly associated with HPV16-positive tumor status among patients with SCCOP (OR, 1.97; 95% CI, 1.03-3.76), but no significant association was observed for the TGF-beta1 C509T or G915C polymorphism. When all variant genotypes were combined, however, SCCOP patients carrying genotypes with any of these TGF-beta1 variants were more than twice as likely to have an HPV16-positive tumor (OR, 2.28; 95% CI, 1.16-4.50) as patients with no variant genotypes. The stratified analysis showed that those under 54 years of age, non-Hispanic white patients, never smokers, and never drinkers with any variant TGF-beta1 genotypes were also more likely to have HPV16-positive tumors. TGF-beta1 polymorphisms may serve as a susceptibility marker for tumor HPV16 status among SCCOP patients, particularly those who were never smokers and never drinkers. Large studies are needed to validate our findings.

Abstract B27: Social representations of human papillomavirus (HPV) in Bogotá, Colombia: A qualitative study

Abstract Introduction: Identifying DNA of Human papillomavirus (HPV) among asymptomatic women has been proposed as a new screening method for cervical cancer control. Screening programs must be preceded by health education. Traditionally, health education is based on scientific information without considering any community cognitive processes. This paper studies HPV social representations constructed upon social interaction between men and women over 25 years of age, living in Bogotá, Colombia. The outcomes will be used as groundwork for an education strategy to promote HPV testing within a primary screening program. Methods: It is a qualitative study based upon symbolic interaccionism. Inter individual communication is precisely the ground where a framework of references is constructed and social representations emerge. Focus group selection was planned using a theoretical population sample. Twelve focus groups were held with 124 men and women from diverse educational status. Information source analysis and graphic analysis of significants were performed. Results: Social representation of HPV involves a series of figurative nuclei that arose from associated meanings linked to scientific information. While women focused on symbols associated to contagion; men focused on its venereal character. Negative feelings were expressed particularly among women with a history of one sexual partner. Figurative nuclei also included long-term uncertainty, need or urgent treatment and feelings of imminent death that are associated to cancer and chronic sexually transmitted infections. The social representation burden of HPV impeded many participants from clearly understanding written information about HPV transmission, clearance and cancer risk. Conclusion: HPV social representations are built into a whole framework of values, which must be deconstructed to allow women full participation in HPV screening programs and to prevent psychosocial adverse effects. Delivering scientific information may not be enough for achieving this purpose. Shared decision making is a communication strategy that must be promoted for anticipatory discussion on HPV-DNA testing to be able to deconstruct different values and meanings particularly its association with promiscuity and venereal diseases. Citation Information: Cancer Prev Res 2010;3(1 Suppl):B27.

Determinants of LSIL Regression in Women from a Colombian Cohort

ObjectiveTo analyze the role of Human Papillomavirus (HPV) and other risk factors in the regression of cervical lesions in women from the Bogotá Cohort. Methods200 HPV positive women with abnormal cytology were included for regression analysis. The time of lesion regression was modeled using methods for interval censored survival time data. Median duration of total follow-up was 9 years. Results80 (40%) women were diagnosed with Atypical Squamous Cells of Undetermined Significance (ASCUS) or Atypical Glandular Cells of Undetermined Significance (AGUS) while 120 (60%) were diagnosed with Low Grade Squamous Intra-epithelial Lesions (LSIL). Globally, 40% of the lesions were still present at first year of follow up, while 1.5% was still present at 5 year check-up. The multivariate model showed similar regression rates for lesions in women with ASCUS/AGUS and women with LSIL (HR=0.82, 95% CI 0.59–1.12). Women infected with HR HPV types and those with mixed infections had lower regression rates for lesions than did women infected with LR types (HR=0.526, 95% CI 0.33–0.84, for HR types and HR=0.378, 95% CI 0.20–0.69, for mixed infections). Furthermore, women over 30 years had a higher lesion regression rate than did women under 30 years (HR=1.53, 95% CI 1.03–2.27). The study showed that the median time for lesion regression was 9 months while the median time for HPV clearance was 12 months. ConclusionsIn the studied population, the type of infection and the age of the women are critical factors for the regression of cervical lesions.

Natural History of Cervical Papilloma Virus Infection in Systemic Lupus Erythematosus — A Prospective Cohort Study

To ascertain the incidence, cumulative prevalence, persistence, and clearance of human papilloma virus (HPV) infection in patients with systemic lupus erythematosus (SLE), and to assess the risk factors for the acquisition and persistence of HPV infection. One hundred forty-four patients with SLE were evaluated at 6-month intervals for up to 3 years. At each visit, a Pap test, a test for HPV DNA, and clinical assessment were performed. The cumulative prevalence of HPV infection increased significantly (12.5% at baseline to 25.0% after 3 years; p = 0.006). Regarding type-specific HPV infection, 18.8% patients experienced 68 incident infections. The cumulative prevalence of high-risk HPV infection (11.1% at baseline to 20.8% after 3 years; p = 0.02) and multiple HPV infection also increased significantly (6.9% at baseline to 16.7% after 3 years; p = 0.009). Half (33/68, 48.5%) of the incident infections persisted for >or= 6 months. Overall, 29/32 (90.6%) of the preexisting infection and 10/68 (14.7%) of the incident infections were cleared. Independent risk factors associated with incident HPV infection included younger age at first sexual intercourse (p = 0.025) and baseline Systemic Lupus International Collaborating Clinics score >or= 1 (p = 0.038). Independent risk factor associated with persistent HPV infection included preexisting HPV infection (p = 0.04) and multiple HPV infection during first incident infection (p = 0.02). High frequency of persistent HPV infection, especially high-risk and multiple HPV infection, may explain why squamous intraepithelial lesions occurred frequently in patients with SLE. Patients with high inflammatory burden are at risk of acquiring HPV infection.

P1001 Carbon dioxide laser vaporization of cervical dysplasia – an effective method for human papillomavirus clearance

International Journal of Gynecology & ObstetricsVolume 107, Issue S2 p. S694-S694 Poster presentations P1001 Carbon dioxide laser vaporization of cervical dysplasia – an effective method for human papillomavirus clearance G. Dimitrov, Search for more papers by this authorE. Dzikova, Search for more papers by this authorI. Andonova, Search for more papers by this authorE. Trajkovska, Search for more papers by this authorL. Hodza, Search for more papers by this author G. Dimitrov, Search for more papers by this authorE. Dzikova, Search for more papers by this authorI. Andonova, Search for more papers by this authorE. Trajkovska, Search for more papers by this authorL. Hodza, Search for more papers by this author First published: 20 November 2009 https://doi.org/10.1016/S0020-7292(09)62487-5AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume107, IssueS2Abstracts of XIX FIGO World Congress of Gynecology and ObstetricsOctober 2009Pages S694-S694 RelatedInformation

PVIII-1 Detection of EBV DNA in patients with hodgkin lymphoma in the Czech Republic: frequency, quantity in plasma, whole blood and lymph node

Objective: The purpose of this study was to determine the long-term tendency for cervical human papillomavirus infections to persist in the general population. Study Design: From 500 women who participated in a 1991 population-based survey, 90 healthy women with normal results of cytologic examination (women with human papillomavirus deoxyribonucleic acid detected and age-matched control women without human papillomavirus deoxyribonucleic acid detected) were interviewed and examined 5 years later colposcopically, cytologically, and with human papillomavirus serologic testing and human papillomavirus deoxyribonucleic acid testing by polymerase chain reaction with 2 different consensus primer pairs (MY09 and MY11 and GP5+ and GP6+), type-specific polymerase chain reaction, and deoxyribonucleic acid sequencing. Results: The 5-year human papillomavirus clearance rate was 92%. Only human papillomavirus type 16 infections persisted. Colposcopic impression of grade 2 cervical intraepithelial neoplasia was associated with persistent human papillomavirus 16 infection (P <.03). Human papillomavirus detection was associated with sexual history. Human papillomavirus type was the only determinant of human papillomavirus persistence. Conclusion: The high clearance rates in a population-based setting with a 5-year follow-up period imply that inclusion of human papillomavirus deoxyribonucleic acid testing in population-based cervical screening programs should target persistent infection. (Am J Obstet Gynecol 2000;183:561-7.)

Natural history of persistent high-risk human papillomavirus infections in Korean women

ObjectiveThis prospective study was performed to evaluate the clearance of high-risk human papillomavirus (HPV) infection and incidence of cytologic abnormality and cervical intraepithelial neoplasia (CIN) during the follow-up of persistent infection in Korean women. MethodsA total of 4170 women who were screened for cervical cancer, were aged 30 years or older, had no abnormal last Pap smear results for 3 years, had no history of treatment for cervical neoplastic disease, and were not pregnant were analyzed for high-risk HPV prevalence using the Hybrid capture (HC) II assay. The 224 women with normal cytology but positive for high-risk HPV DNA using the HC-II assay were analyzed for their clearance of HPV infection. ResultsThe median time to clearance in women with initially normal cytology was 7.5 months from initial detection (95% CI, 5.2–9.8 months). There were significant differences in the median time to clearance (4.5 vs. 14.5 months, p <0.001) of high-risk HPV infection between women with the initial relative light unit/ cutoff (RLU/CO) ratio values <10.0 and ≥10.0, as determined by the HC-II assay. In Kaplan–Meier analysis, probability of development of cytologic abnormalities, CIN and high-grade CIN was 38.2%, 21.7% and 8.5% respectively at 24 months of persistent high-risk HPV infection. ConclusionThe prevalence and clearance of high-risk infection in Korean women was similar to that in Western countries. Persistent high-risk HPV infection was associated with high viral load.

Cervical Human Papillomavirus Incidence and Persistence in a Cohort of HIV-Negative Women in Zimbabwe

Persistent infections with oncogenic human papillomavirus (HPV) types are causally related to cervical cancer. Little is known about the distribution of HPV types, independent risk factors of incidence and persistence, and patterns of persistence in sub-Saharan Africa. A cohort of 2040 Zimbabwean women was enrolled in a randomized trial assessing the effect of diaphragm/gel provision on human immunodeficiency virus and HPV acquisition. Data from the study arms were pooled for this analysis because diaphragm/gel provision did not affect HPV acquisition and clearance. Clinicians collected cervical samples for HPV testing at enrollment, 12 months, and exit (median 21 months). HPV prevalence was 24.5% for any HPV type and 16.1% for oncogenic types. HPV incidence at 12 months was 23.3% for any HPV type and 11.4% for oncogenic types. HPV58 had the highest baseline prevalence (5.0%) and incidence (2.4%). Type-specific persistence was 29.8% among all HPV infections over a median of 21 months of follow-up. Baseline predictors of incident HPV infection were younger age, having more than 1 lifetime sexual partner, infrequent condom use, herpes simplex virus-2 positive serology, and having a sexually transmissible infection or a different HPV type at enrollment. Baseline predictors of persistent HPV infection were younger age, having more than 1 lifetime sexual partner, and having a high-risk partner. The novel association between herpes simplex virus-2 seropositivity and incident HPV infection warrants further investigation. Having a high-risk partner is a potentially modifiable risk factor for persistent HPV infection. The relatively high prevalence of HPV58 has implications for vaccine development.

IFNG (+874 T/A) Polymorphism and Cervical Intraepithelial Neoplasia in Brazilian Women

Our objective was to investigate the relationship between IFNG (+874 T/A) polymorphism and cervical intraepithelial neoplasia (CIN) in a population of Brazilian women. Ninety-six women, CIN II (48) and CIN III (48) and 50 normal controls, were enrolled in this study. DNA was extracted from blood samples by the salting out method and polymerase chain reaction (PCR) amplified. IFNG genotyping was performed by the PCR-Sequence Specific Primer method, using the Cytokine Genotyping Tray. There were no differences in genotypic frequencies between CIN patients and controls. However, after sample stratification into CIN II and III, a higher frequency of the AA genotype in CIN II versus control group (P = 0.05) was observed. When the comparison was performed between CIN groups, a higher frequency of the AA genotype in CIN II versus CIN III (P = 0.05) was observed. This study suggests that IFNG +874 T/A polymorphism responsible for the genetic differences in interferon (IFN)-gamma production may influence the human papillomavirus (HPV) clearance and cervical malignant progression. Further understanding of the role of this cytokine may contribute to the development of a biomarker of HPV infection and resulting in the improvement of squamous intraepithelial lesions treatment.

Preclinical models of HPV+ and HPV− HNSCC in mice: An immune clearance of HPV+ HNSCC

To investigate whether human papilloma virus (HPV)-specific immune mechanisms can result in tumor clearance, we have created HPV+ and HPV- tonsil cells that form squamous cancers in immune-competent mice. Here, we determine that an immune-specific response can clear HPV+ tumor cells and the cellular requirements to mediate this tumor clearance. Through the benefit of this model, we use in vitro and in vivo methods to better understand how HPV+ cells are rejected. RESULT.: The data show that an in vivo antigen-specific antitumor response is generated to HPV+ transformed cells and that this response requires CD4+ and CD8+ cells to mount this antitumor response. The findings from this preclinical model will have implications not only in understanding human disease but also as a valuable model for testing immunotherapeutic strategies for HPV+ head and neck cancer.

Duration and Clearance of Anal Human Papillomavirus (HPV) Infection among Women: The Hawaii HPV Cohort Study

The association of anal cancer with human papillomavirus (HPV) infection is well established; however, little is known about the epidemiology of anal HPV in healthy women. We investigated patterns of duration and clearance of anal HPV infection in a cohort of healthy women in Hawaii. Viral and nonviral determinants of anal HPV clearance were examined in a longitudinal cohort study of 431 sexually active women. At baseline and at 4-month intervals, interviews were conducted and cervical and anal cell specimens were obtained for detection of HPV DNA. Of the 431 women, 50% experienced a total of 414 incident anal HPV infections, reported at 1 clinic visits from baseline through a follow-up period of average duration of 1.2 years. Of these infections, 58% cleared during follow-up. The clearance rate for a high-risk anal infection was 9.2 per 100 woman-months (95% confidence interval [CI], 6.9-11.9 per 100 woman-months), with a median duration of 150 days (95% CI, 132-243 days). The slowest clearing high-risk HPV types were HPV-59 (median clearance time, 350 days) and HPV-58 (median clearance time, 252 days). The median clearance times for HPV-16 and HPV-18, the predominant types associated with anal cancer, were 132 days and 212 days, respectively. Nonviral factors that delayed clearance of anal HPV included douching, long-term tobacco smoking, and anal sex. The majority of anal HPV infections resolve in a relatively short time. Although anal HPV is commonly acquired in healthy women, its rapid clearance suggests limited efficacy of HPV testing as an anal cancer screening tool.