Human Papillomavirus Clearance Research Articles

Higher HPV16 and HPV18 Penile Viral Loads Are Associated With Decreased Human Papillomavirus Clearance in Uncircumcised Kenyan Men

Higher HPV16 and HPV18 Penile Viral Loads Are Associated With Decreased Human Papillomavirus Clearance in Uncircumcised Kenyan Men

Bacterial vaginosis and inflammatory response showed association with severity of cervical neoplasia in HPV-positive women.

Vaginal infections may affect susceptibility to and clearance of human papillomavirus (HPV) infection and chronic inflammation has been linked to carcinogenesis. This study aimed to evaluate the association between bacterial vaginosis (BV) and inflammatory response (IR) with the severity of cervical neoplasia in HPV-infected women. HPV DNA was amplified using PGMY09/11 primers and genotyping was performed using a reverse line blot hybridization assay in 211 cervical samples from women submitted to excision of the transformation zone. The bacterial flora was assessed in Papanicolaou stained smears, and positivity for BV was defined as ≥ 20% of clue cells. Present inflammatory response was defined as ≥ 30 neutrophils per field at 1000× magnification. Age higher than 29 years (OR:1.91 95% CI 1.06-3.45), infections by the types 16 and/or 18 (OR:1.92 95% CI 1.06-3.47), single or multiple infections associated with types 16 and/or 18 (OR: 1.92 CI 95% 1.06-3.47), BV (OR: 3.54 95% CI 1.62-7.73) and IR (OR: 6.33 95% CI 3.06-13.07) were associated with severity of cervical neoplasia (CIN 2 or worse diagnoses), while not smoking showed a protective effect (OR: 0.51 95% CI 0.26-0.98). After controlling for confounding factors, BV(OR: 3.90 95% CI 1.64-9.29) and IR (OR: 6.43 95% CI 2.92-14.15) maintained their association with the severity of cervical neoplasia. Bacterial vaginosis and inflammatory response were independently associated with severity of cervical neoplasia in HPV-positive women, which seems to suggest that the microenvironment would relate to the natural history of cervical neoplasia.

Incidence and clearance of anal high-risk human papillomavirus in HIV-positive men who have sex with men: estimates and risk factors.

To estimate incidence and clearance of high-risk human papillomavirus (HR-HPV), and their risk factors, in men who have sex with men (MSM) recently infected by HIV in Spain; 2007-2013. Multicenter cohort. HR-HPV infection was determined and genotyped with linear array. Two-state Markov models and Poisson regression were used. We analysed 1570 HR-HPV measurements of 612 MSM over 13 608 person-months (p-m) of follow-up. Median (mean) number of measurements was 2 (2.6), median time interval between measurements was 1.1 years (interquartile range: 0.89-1.4). Incidence ranged from 9.0 [95% confidence interval (CI) 6.8-11.8] per 1000 p-m for HPV59 to 15.9 (11.7-21.8) per 1000 p-m for HPV51. HPV16 and HPV18 had slightly above average incidence: 11.9/1000 p-m and 12.8/1000 p-m. HPV16 showed the lowest clearance for both 'prevalent positive' (15.7/1000 p-m; 95% CI 12.0-20.5) and 'incident positive' infections (22.1/1000 p-m; 95% CI 11.8-41.1). More sexual partners increased HR-HPV incidence, although it was not statistically significant. Age had a strong effect on clearance (P-value < 0.001) due to the elevated rate in MSM under age 25; the effect of HIV-RNA viral load was more gradual, with clearance rate decreasing at higher HIV-RNA viral load (P-value 0.008). No large variation in incidence by HR-HPV type was seen. The most common incident types were HPV51, HPV52, HPV31, HPV18 and HPV16. No major variation in clearance by type was observed, with the exception of HPV16 which had the highest persistence and potentially, the strongest oncogenic capacity. Those aged below 25 or with low HIV-RNA- viral load had the highest clearance.

Human papillomavirus infection and lymphoma incidence using cervical conization as a surrogate marker: a Danish nationwide cohort study.

Persistent human papillomavirus (HPV) infection may promote carcinogenesis by hyperactivation of the immune system. We, therefore, explored the associations between HPV infection and risk of Hodgkin and non-Hodgkin lymphoma in a nationwide cohort study using conization as a surrogate marker. We identified all Danish women who underwent conization between 1978 and 2011. We computed standardized incidence ratios and 95% confidence intervals for Hodgkin and non-Hodgkin lymphoma based on national cancer incidence rates. Among 87 435 women who underwent conization, we noted an increased incidence of Hodgkin (standardized incidence ratio 1.48, 95% confidence interval 1.05-2.02) but only a slight increase for non-Hodgkin lymphoma (standardized incidence ratio 1.10, 95% confidence interval 0.97-1.25). As measured by conization, HPV infection is associated with an increased risk of lymphoma. This association may be attributable to a chronic immune activation induced by persistent HPV infection and/or failure of the immune system both to clear HPV infection and to control lymphoma development. Copyright © 2015 John Wiley & Sons, Ltd.

Undetected human papillomavirus DNA and uterine cervical carcinoma: Association with cancer recurrence.

The time course of human papillomavirus (HPV) DNA clearance was studied in patients with carcinoma of the cervix during follow-up after primary radical radiotherapy (RT). This study investigated the relationship between timing of HPV clearance and RT effectiveness. A total of 71 consecutive patients who were treated for cervical cancer with primary radical radiotherapy and high-dose rate intracavitary brachytherapy with or without chemotherapy were enrolled in the study. Samples for HPV DNA examination were taken before (1) treatment, (2) every brachytherapy, and (3) every follow-up examination. The times when HPV DNA was undetected were analyzed for association with recurrence-free survival. HPV DNA was not detected in 13 patients (18 %) before RT. Of the 58 patients with HPV DNA detected before treatment, HPV DNA was not detected in 34 % during treatment and in 66 % after the treatment. Within 6 months after RT, HPV DNA was detected in 0 % of all patients. The patients were followed up for a median period of 43 months (range 7-70 months). In all, 20 patients were found to develop recurrence. The 3-year cumulative disease-free survival (DFS) rate was 71 ・} 5.4 % for all 71 patients. In multivariate analysis, DFS was significantly associated with HPV (detected vs. not detected) with a hazard ratio of 0.07 (95 % confidence interval 0.008-0.6, p = 0.009). In this study, patients in whom HPV was not detected had the worst prognosis. Six months after RT, HPV DNA was detected in 0 % of the patients. Patients in whom HPV DNA could not be detected before treatment need careful follow-up for recurrence and may be considered for additional, or alternative treatment.

The Effect of Cryotherapy on Human Papillomavirus Clearance Among HIV-Positive Women in Lusaka, Zambia.

We sought to investigate the progression of human papillomaviruses (HPV) infection in HIV-positive women after cryotherapy. We examined changes in detection of high-risk HPV (hrHPV) cervical infections among HIV-infected women over a 12-week period after cryotherapy using stored specimens from a cohort study conducted between June 2009 and March 2011 in Lusaka, Zambia. Samples from visits at baseline and weeks 4, 8, and 12 were tested using the Roche Linear Array assay. A total of 89 women were included in the analysis. The median age was 32 years (interquartile range [IQR], 28-36 years). The median CD4+ cell count was 350 cells/μL (IQR, 214-470 cells/μL), and 66% of women were receiving antiretroviral therapy. At baseline, the prevalence of hrHPV was 91% (95% confidence interval [CI], 83%-95%). HPV45 was the most common HPV type, present in (30%) women, followed by HPV16 (27%), HPV18 (27%), HPV51 (20%), and HPV58 (22%). Among women with valid results both at baseline and 12 weeks, 25% (17/67) cleared their initial hrHPV infection within 12 weeks of treatment, although 65% (11/17) had new hrHPV types detected. Cryotherapy led to clearance of 25% of hrHPV infections within 12 weeks of treatment. However, hrHPV infection remained persistent in most women, and new hrHPV types were detected often, explaining the high rate of persistence and recurrence of cervical disease in this population. Continued efforts to scale up HPV vaccination and cervical screening should remain a priority in high HIV burden settings such as Zambia.

Abstract A55: PD-1 blockade synergizes with cisplatin radiation therapy aiding in clearance of murine HPV+ oropharyngeal carcinoma

Abstract Squamous cell carcinomas of the head and neck (SCCHN) are the 6th most common malignancy world-wide with approximately 650,000 diagnoses per year. Human papillomavirus (HPV) causes up to 80% of oropharyngeal (tonsil/base of tongue) SCCHN. Despite presenting at an advanced stage, multiple studies show that HPV+ SCCHN are more curable relative to their HPV- counterparts. Clearance of SCCHN during treatment with cisplatin radiation therapy (CRT) is not only related to direct cytotoxicity, but is also dependent on immune mediated clearance. This immune clearance is strongly dependent on an intact CD4+ and CD8+ cellular response to tumor cells harboring these viral oncogenes. Furthermore, the immune system recognizes and clears HPV + SCCHN only after the start of CRT. The immunologic tolerance to these cancers prior to treatment could be explained by immune checkpoints aimed at preventing unregulated immune activity. The programmed death 1 receptor (PD-1) and its ligand, PD-L1, are one such checkpoint axis. Recent data suggests that the PD-1:PD-L1 pathway may play an important role in immune resistance in head and neck cancer. We evaluated PD-1 in combination with CRT in an immune competent HPV+ SCCHN mouse model. HPV + mouse SCCHN cells were injected subcutaneously into immune competent mice and tumors were treated after growing to palpable size. Using the mouse analog to the human PD-1 blocker, pembrolizumab, we determined that while single-agent therapy does not have significant activity on primary disease or distant metastasis, PD-1 blockade strongly synergizes with CRT. An overall survival of 58% was evident in mice treated with combination PD-1 and CRT versus 8% in mice treated with isotype control (IgG1) in combination with CRT (p = 0.006). These studies provide the impetus for future work investigating less toxic induction of immune responses in combination with blockade of immune checkpoint pathways. Citation Format: Daniel W. Vermeer, Steven Powell, William C. Spanos, John H. Lee. PD-1 blockade synergizes with cisplatin radiation therapy aiding in clearance of murine HPV+ oropharyngeal carcinoma. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr A55.

Associations of Anogenital Low-Risk Human Papillomavirus Infection With Cancer and Acquisition of HIV.

α-Mucosal human papillomavirus (HPV) types are implicated in a range of clinical conditions and categorized as "low-risk" (LR) and "high-risk" (HR) types according to their degree of association with cervical cancers. The causative role of LR HPV infection in the development of anogenital warts and in low-grade squamous intraepithelial lesions is well established. In addition, there is a growing body of evidence that infection with LR HPV types may be associated with an elevated risk of cancers and potentiation of coinfections. Prospective and case-control studies consistently report a higher risk of anogenital cancers in men and women with a history of anogenital warts. Based on currently available evidence, this higher risk may be due to shared exposure to HR HPV types or an underlying immune impairment, rather than a direct role of LR HPV types in subsequent cancer risk. Data also suggest that infection with LR HPV, HR HPV, or both may increase the risk of HIV acquisition, although the relative contribution of different HPV types is not yet known. There is also evidence implicating HPV clearance, rather than HPV infection, in increased risk of HIV acquisition.

P0063 HPV infection and lymphoma incidence using cervical conisation as a surrogate marker: A Danish nationwide cohort study

Background Persistent human papillomavirus (HPV) infection may promote carcinogenesis by hyperactivation of the immune system. We therefore explored the associations between HPV infection and risk of Hodgkin’s and non-Hodgkin lymphoma in a nationwide cohort study using conisation as a surrogate marker. Methods We identified all Danish women who underwent conisation between 1978 and 2011. We computed standardised incidence ratios and 95% confidence interval (CI) for Hodgkin’s and non-Hodgkin lymphomas based on rates of national cancer incidence. Findings Of 87,435 women who underwent conisation (1978–2011), we noted an increased incidence of Hodgkin’s lymphomas (standardised incidence ratio [SIR] 1.48, 95% CI 1.05–2.02), but only a slight increase in incidence for non-Hodgkin lymphoma (SIR 1.10, 95% CI 0.97–1.25). Interpretation HPV infection, as measured by conisation, is associated with an increased risk of lymphoma. This association may be attributable to a chronic immune activation induced by persistent HPV infection or poor clearance of HPV.

A joint model of persistent human papillomavirus infection and cervical cancer risk: Implications for cervical cancer screening.

New cervical cancer screening guidelines in the US and many European countries recommend that women get tested for human papillomavirus (HPV). To inform decisions about screening intervals, we calculate the increase in precancer/cancer risk per year of continued HPV infection. However, both time to onset of precancer/cancer and time to HPV clearance are interval-censored, and onset of precancer/cancer strongly informatively censors HPV clearance. We analyze this bivariate informatively interval-censored data by developing a novel joint model for time to clearance of HPV and time to precancer/cancer using shared random-effects, where the estimated mean duration of each woman's HPV infection is a covariate in the submodel for time to precancer/cancer. The model was fit to data on 9,553 HPV-positive/Pap-negative women undergoing cervical cancer screening at Kaiser Permanente Northern California, data that were pivotal to the development of US screening guidelines. We compare the implications for screening intervals of this joint model to those from population-average marginal models of precancer/cancer risk. In particular, after 2 years the marginal population-average precancer/cancer risk was 5%, suggesting a 2-year interval to control population-average risk at 5%. In contrast, the joint model reveals that almost all women exceeding 5% individual risk in 2 years also exceeded 5% in 1 year, suggesting that a 1-year interval is better to control individual risk at 5%. The example suggests that sophisticated risk models capable of predicting individual risk may have different implications than population-average risk models that are currently used for informing medical guideline development.

HPV and Adolescent Males with HIV 2007-2009

Objective: Human Papillomavirus (HPV) infection is found to be more prevalent in HIV-infected than uninfected men (73% vs. 43%). Young men who have sex with men (YMSM) with HIV with HPV anal lesions often deny or are unaware of these lesions. Unless screened, these lesions will remain undiagnosed with a potential for transmission to sexual partners and disease progression. We explored screening practices for HPV and therapeutic/diagnostic outcome of HPV screening among YMSM with HIV, including co-infection with other STIs. Methods: Chart review of all HIV+ adolescent males, age 13-24 years, reporting MSM, engaged in care, 2007-2009, at an inner city HIV clinic for adolescents and young adults. Results: The average number of males enrolled in care was 143 per year (range 127-166) and none received HPV vaccination. By visual inspection 50 YMSM were identified with anal HPV lesions: 46% received anal cytology, 30% were identified as abnormal (ASCUS, LGSIL, or HGSIL); 90% received medical treatment (Imiquimod or Podophylline); 72.3% with no evidence that lesions cleared; 68.6% were referred to Colorectal surgical clinic. In addition, 62% had STIs diagnosed: syphilis (42%); gonorrhea (39%); chlamydia (26%), and HSV (19%), Hepatitis B (6%); Hepatitis C (3%). Clearance of HPV was associated with having more than one STI (p=0.03). Conclusions: Detecting genital warts by visual inspection without acetic acid is an insensitive screening, thus the number of males suspected to have HPV would be higher than the 50 identified by visual inspection. In this cohort of HIV+ YMSM with HPV, a third were identified as having abnormal cytology, which is worrisome for infection with oncogenic HPV subtypes. Not all received HPV medical and or referred for surgical treatment. The majority of the cohort was co-infected with STIs, and having more than one STI was associated with clinical clearance of HPV lesions

Type-specific persistence or regression of human papillomavirus genotypes in women with cervical intraepithelial neoplasia 1: A prospective cohort study.

ObjectiveTo evaluate the type-specific human papillomavirus (HPV) persistence or regression in women with or less than low-grade cervical intraepithelial neoplasia (CIN).MethodsThis prospective cohort study included patients with or less than cytological low-grade squamous intraepithelial lesion (or histologically CIN 1 when biopsy was performed) combined with HPV infection. The cohort was collected from July 2006 to November 2011 at Korea University Guro Hospital. Follow-up was performed with liquid-based Papanicolaou test, hybrid capture 2 test, AnyplexTM II HPV 28 Detection, colposcopic biopsy if necessary every 4 months. All patients were prospectively observed without treatment.ResultsOne hundred and thirty-seven patients were enrolled. Of these, 21 patients whose minimum follow-up periods were less than 8 months were excluded. Finally, one hundred sixteen patients were included and followed-up. Median follow-up period was 16 months. In case of high-risk HPVs, HPV 53 was the most prevalent type, followed by HPV 52, 68, 66, and 16. HPV 16 took 10.6 months to regress spontaneously, which was the longest period among the 10 most prevalent high-risk HPV genotypes. In case of spontaneous regression, HPV clearance was always accompanied by lesion clearance. A total of 13 patients showed disease progression either cytologically or histologically. Two cases of CIN 3 were confirmed by colposcopy-directed biopsy during follow-up, which were subsequently managed by conization.ConclusionHPV 16 is the most persistent HPV genotypes. Studies with longer term follow-up and larger sample size are needed to demonstrate whether persistence of HPV 16 is directly correlated with progression of low-grade lesions.

The Effect of Cryotherapy on Human Papillomavirus Clearance Among HIV-Positive Women in Lusaka, Zambia

The Effect of Cryotherapy on Human Papillomavirus Clearance Among HIV-Positive Women in Lusaka, Zambia

Risk factors for acquisition and clearance of oral human papillomavirus infection among HIV-infected and HIV-uninfected adults.

Human papillomavirus (HPV) causes the majority of oropharyngeal cancers in the United States, yet the risk factors for and natural history of oral HPV infection are largely unknown. In 2010-2011, a US-based longitudinal cohort study of 761 human immunodeficiency virus (HIV)-infected and 469 at-risk HIV-uninfected participants from the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study was initiated. Semiannually collected oral rinses were evaluated for 37 HPV genotypes using the Roche LINEAR ARRAY HPV Genotyping Test (Roche Molecular Systems, Pleasanton, California), and factors associated with oral HPV incidence and clearance were explored using adjusted Wei-Lin-Weissfeld modeling. Through 2013, the 2-year cumulative incidence of any type of oral HPV infection was 34% in HIV-infected persons and 19% in HIV-uninfected persons. However, many of these infections cleared. Seven percent of incident infections and 35% of prevalent infections persisted for at least 2 years. After adjustment for other risk factors, HIV infection (adjusted hazard ratio = 2.3, 95% confidence interval: 1.7, 3.2), reduced current CD4 cell count, and increased numbers of oral sex and "rimming" partners increased the risk of incident oral HPV infection, whereas male sex, older age, and current smoking increased the risk of oral HPV persistence (each P < 0.05). This helps explain the consistent associations observed between these factors and prevalent oral HPV infection in previous cross-sectional studies.

Oral prevalence and clearance of oncogenic human papilloma virus in a rehabilitation community for substance abusers in Italy: a case of behavioral correction?

Human papilloma virus oral infection can be related to several factors including HIV infection, cigarette smoking, marijuana consumption and number of sexual partners. We conducted a study on oral HPV prevalence and clearance among the hosts of the San Patrignano community, a population considered at "high-risk" for HPV due to their previous habits. From March 2007 to September 2010 all subjects were submitted to oropharyngeal brushing and saliva collection at baseline, after 6, 12 and 48 months (for subjects HPV positive at baseline). Samples were analyzed to detect HPV DNA and virus genotypes. The correlation between HPV prevalence and demographic, behavioral or immunological characteristics was assessed. Among 194 subjects, 30 (15%) were HPV positive with 25 (13%) high-risk (HR)-HPV at baseline brushing. At 12 months HPV infection was cleared in all cases. However at 48 months HPV was newly detected in 33% of subjects. A correlation between time spent in the community and increase in the ratio of "low-risk" (LR) HPV and HR-HPV was observed. HPV infection was not associated with age, gender, HIV status, HCV, alcohol and/or drug exposure, number of years spent in community, sex with drug-addicts and condom use. Only AIDS under antiretroviral treatment was inversely correlated with the risk of infection. At 1 year a complete HPV clearance was observed which could be related to adoption of healthier lifestyles of participants. New HPV infections were detected even in the absence of the recognized and declared risky behavioral factors, suggesting a re-expression from a latent infection.

A randomized study of hexaminolevulinate photodynamic therapy in patients with cervical intraepithelial neoplasia 1/2

The objective of the study was to investigate the efficacy and safety of hexaminolevulinate (HAL) photodynamic therapy (PDT), a novel therapy for women with cervical intraepithelial neoplasia (CIN)1/2, to define the appropriate population and endpoints for a phase 3 program. This was a double-blind, randomized, placebo-controlled, dose-finding study that included a total of 262 women with biopsy-confirmed CIN 1/2 based on local pathology. Patients received 1 or 2 topical treatments of HAL hydrochloride 0.2%, 1%, 5%, and placebo ointment and were evaluated for response after 3-6 months based on biopsy, Papanicolaou test, and oncogenic human papillomavirus (HPV) test. All efficacy analyses were performed on blinded central histology review to avoid interreader variability. Adverse events, blood biochemistry, and vital signs were assessed after 3 months. There were no statistically significant differences between placebo and either the CIN 1 or combined CIN 1/2 populations. A cleardose effect with a statistically significant response in theHAL5% group of 95% (18/19 patients) compared to 57% (12/21 patients) in the placebo group (P < .001) was observed at 3months in women with CIN 2, including an encouraging 83% (5/6 patients) clearance of HPV 16/18 compared to 33% (2/6 patients) in the placebo group at 6 months. The treatment was easy to use and well accepted by patients and gynecologists. Only local self-limiting adverse reactions including discharge, discomfort, and spotting were reported. HAL PDT is a novel therapy that shows promise in the treatment of CIN 2 including clearance of oncogenic HPV, but not of CIN 1. The positive risk/benefit balance makes HAL PDT a tissue-preserving alternative in women of childbearing age who wish to preserve the cervix. Confirmatory studies are planned.

Expression of nucleic acid-sensing Toll-like receptors predicts HPV16 clearance associated with an E6-directed cell-mediated response.

Toll-like receptors (TLRs), important in rapid clearance of incident human papillomavirus (HPV) infections, may also be important in shaping the adaptive response to persistent infections. We examined here the association between TLR expression and clearance of HPV16 infections following periods of persistence, using longitudinal TLR measurements and a time-to-clearance analysis, as well as the interaction between TLRs and adaptive, cell-mediated responses involved in clearance. TLR2, TLR3, TLR7, TLR8 and TLR9 mRNA expression were measured in cervical cytobrush samples by quantitative PCR. Responses to the HPV16 E6 and E7 oncoproteins were measured by an interferon-γ immunospot assay. Bivariable and multivariable Cox proportional hazard models were used to estimate the effect of TLRs on HPV16 clearance. Higher expression of TLR3 or TLR7 at an HPV16-positive visit was a significant (p ≤ 0.05) predictor of clearance by the following visit, in both unadjusted and adjusted (for smoking and oral contraceptive use) models. In women with, but not those without, a positive response to E6, higher expression of TLR3 (hazard ratio: 1.2 [95% confidence interval: 1.04-1.39], p = 0.012), TLR7 (1.39 [1.14-1.7], p = 0.001), TLR8 (1.37 [1.11-1.69], p = 0.003), or TLR9 (1.53 [1.13-2.08], p = 0.006) was significantly associated with clearance, revealing an important link between innate and adaptive immunity in the control of HPV infections following periods of persistence.

TLR9 is expressed in human papillomavirus-positive cervical cells and is overexpressed in persistent infections

Control of human papillomavirus (HPV) infection involves the activation of Toll-like receptors (TLRs), key components of the mucosal antiviral response. Available studies on TLR expression in HPV-positive cervical cells are limited and reported conflicting results.This study quantified TLR 2, 3, 4, 7 and 9 transcripts in low-risk (LR) and high-risk (HR) HPV-positive and HPV-negative cervical samples from 154 women attending a gynaecological clinic.Expression levels of TLR 2, 3, 4 and 7 did not differ among samples, whereas TLR9 levels were quite significantly higher in LR and marginally significant in HR HPV-positive samples, with respect to the HPV-negative samples. Interestingly, in a subgroup of women with documented previous HPV-infection, TLR9 levels were extremely higher in patients persistently positive to the same HPV genotype for more than 1 year, with respect to women who cleared HPV infection and to those re-infected with a different genotype.These findings implicate TLR9 in the response to LR and HR HPVs, including HPV 16 known to interfere with TLR9 transcription in cell lines. Elevated TLR9 levels without HPV clearance in persistently infected women could drive inflammation thereby contributing to cervical cancer risk.

An updated natural history model of cervical cancer: derivation of model parameters.

Mathematical models of cervical cancer have been widely used to evaluate the comparative effectiveness and cost-effectiveness of preventive strategies. Major advances in the understanding of cervical carcinogenesis motivate the creation of a new disease paradigm in such models. To keep pace with the most recent evidence, we updated a previously developed microsimulation model of human papillomavirus (HPV) infection and cervical cancer to reflect 1) a shift towards health states based on HPV rather than poorly reproducible histological diagnoses and 2) HPV clearance and progression to precancer as a function of infection duration and genotype, as derived from the control arm of the Costa Rica Vaccine Trial (2004-2010). The model was calibrated leveraging empirical data from the New Mexico Surveillance, Epidemiology, and End Results Registry (1980-1999) and a state-of-the-art cervical cancer screening registry in New Mexico (2007-2009). The calibrated model had good correspondence with data on genotype- and age-specific HPV prevalence, genotype frequency in precancer and cancer, and age-specific cancer incidence. We present this model in response to a call for new natural history models of cervical cancer intended for decision analysis and economic evaluation at a time when global cervical cancer prevention policy continues to evolve and evidence of the long-term health effects of cervical interventions remains critical.

Disparity in the persistence of high-risk human papillomavirus genotypes between African American and European American women of college age.

Cervical cancer incidence and mortality rates are higher in African Americans than in European Americans (white, non-Hispanic of European ancestry). The reasons for this disparity are not known. We recruited a population-based longitudinal cohort of 326 European American and 113 African American female college freshmen in Columbia, South Carolina, to compare clearance of high-risk human papillomavirus (HR-HPV) infection between ethnicities. HPV testing and typing from samples obtained for Papanicolaou testing occurred every 6 months. African American participants had an increased risk of testing positive for HR-HPV, compared with European American participants, but the frequency of incident HPV infection was the same in African American and European American women. Thus, exposure to HPV could not explain the higher rate of HPV positivity among African American women. The time required for 50% of participants to clear HR-HPV infection was 601 days for African American women (n = 63) and 316 days for European American women (n = 178; odds ratio [OR], 1.61; 95% confidence interval [CI], 1.08-2.53). African American women were more likely than European American women to have an abnormal result of a Papanicolaou test (OR, 1.58; 95% CI, 1.05-2.39). We propose that the longer time to clearance of HR-HPV among African American women leads to increased rates of abnormal results of Papanicolaou tests and contributes to the increased rates of cervical cancer observed in African American women.