Natural History of HPV Infection Across the Lifespan: Role of Viral Latency.

Large-scale epidemiologic studies have been invaluable for elaboration of the causal relationship between persistent detection of genital human papillomavirus (HPV) infection and the development of invasive cervical cancer. However, these studies provide limited data to adequately inform models of the individual-level natural history of HPV infection over the course of a lifetime, and particularly ignore the biological distinction between HPV-negative tests and lack of infection (i.e., the possibility of latent, undetectable HPV infection). Using data from more recent epidemiological studies, this review proposes an alternative model of the natural history of genital HPV across the life span. We argue that a more complete elucidation of the age-specific probabilities of the alternative transitions is highly relevant with the expanded use of HPV testing in cervical cancer screening. With routine HPV testing in cervical cancer screening, women commonly transition in and out of HPV detectability, raising concerns for the patient and the provider regarding the source of the positive test result, its prognosis, and effective strategies to prevent future recurrence. Alternative study designs and analytic frameworks are proposed to better understand the frequency and determinants of these transition pathways

Acceptability of HPV vaccine implementation among parents in India.

Due to high cervical cancer rates and limited research on human papillomavirus (HPV) vaccine acceptability in India, the research team examined parental attitudes toward HPV vaccines. Thirty-six interviews with parents were conducted to assess sexually transmitted infection (STI)-related knowledge and HPV-specific vaccine awareness and acceptability. Despite limited knowledge, parents had positive views toward HPV vaccines. Common barriers included concerns about side effects, vaccine cost, and missing work to receive the vaccine. Parents were strongly influenced by health care providers' recommendations. Our findings suggest that addressing parental concerns, health worker training and polices, and efforts to minimize cost will be central to successful HPV vaccine implementation

Baseline assessment of prevalence and geographical distribution of HPV types in Chile using self-collected vaginal samples

<p>Abstract</p> <p>Background</p> <p>Chile has broad variations in weather, economics and population from the far desert north (Region 1) to the cold, icy south (Region 12). A home-based self-collected vaginal sampling was nested in the 2003 Chilean population-based health survey in order to explore the possibility of a type-specific geographical variation for human papillomavirus</p> <p>Methods</p> <p>The population was a national probability sample of people 17 years of age and over. Consenting women provided self-collected cervicovaginal swabs in universal collection media (UCM). DNA was extracted and typed to 37 HPV genotypes using PGMY consensus PCR and line blot assay. Weighted prevalence rates and adjusted OR were calculated.</p> <p>Results</p> <p>Of the 1,883 women participating in the health survey, 1,219 (64.7%) provided a cervicovaginal sample and in 1,110 (56.2% of participants and 66.5% of those eligible) the samples were adequate for analysis. Refusal rate was 16.9%. HPV prevalence was 29.2% (15.1% high-risk HPV and 14.1% low-risk HPV). Predominant high-risk types were HPV 16, 52, 51, 56 and 58. Predominant low-risk HPVs were HPV 84, CP6108, 62, 53 and 61. High-risk and low-risk HPV rates were inversely correlated between the regions. High-risk HPV prevalence was highest among the youngest women, whereas low-risk HPV increased slightly with age.</p> <p>Conclusion</p> <p>Self-obtained vaginal sampling is adequate for monitoring HPV in the community, for identifying high-risk areas, and for surveying the long term impact of interventions.</p

Considerations for Child Cancer Survivors and Immunocompromised Children to Prevent Secondary HPV-associated Cancers

Survivors of childhood cancer and other immunocompromised children are at high risk for the development of secondary Human Papillomavirus (HPV)-associated cancers. In this overview, the authors examine the epidemiology of vaccine efficacy, the natural history of HPV infections, and accelerated HPV-associated cancer development in these populations. The authors highlight the opportunities for preventive care and future research directives

Indian women with higher serum concentrations of folate and vitamin B12 are significantly less likely to be infected with carcinogenic or high-risk (HR) types of human papillomaviruses (HPVs)

BACKGROUND: Studies conducted in the USA have demonstrated that micronutrients such as folate and vitamin B12 play a significant role in modifying the natural history of high-risk human papillomaviruses (HR-HPVs), the causative agent for developing invasive cervical cancer (CC) and its precursor lesions. OBJECTIVE: The purpose of the current study was to investigate whether these micronutrients have similar effects on HR-HPV infections in Indian women. METHODS: The associations between serum concentrations of folate and vitamin B12 and HR-HPV infections were evaluated in 724 women who participated in a CC screening study in the southern state of Andhra Pradesh, India. Serum folate and vitamin B12 concentrations were measured by using a competitive radio-binding assay. Digene hybrid capture 2 (HC2) assay results were used to categorize women into two groups, positive or negative for HR-HPVs. Unconditional logistic regression models specified a binary indicator of HC2 (positive/negative) as the dependent variable and serum folate concentrations combined with serum vitamin B12 concentrations as the independent predictor of primary interest. Models were fitted, adjusting for age, education, marital status, parity, type of fuel used for cooking and smoking status. RESULTS: Women with higher concentrations of serum folate (>6 ng/mL) and vitamin B12 (>356 pg/mL) were at lower risk of being positive for HR-HPVs compared to those with serum folate ≤6 ng/mL and serum vitamin B12 ≤ 356 pg/mL (odds ratio = 0.26; 95% confidence interval: 0.08-0.89; P = 0.03). CONCLUSIONS: These results demonstrated that improving folate and vitamin B12 status in Indian women may have a beneficial impact on the prevention of CC. Micronutrient based interventions for control of HR-HPV infections may represent feasible alternatives to vaccine based approaches to HPV disease prevention, which are currently unaffordable for use in resource limited areas in rural India

Effectiveness of VIA, Pap, and HPV DNA Testing in a Cervical Cancer Screening Program in a Peri-Urban Community in Andhra Pradesh, India

BACKGROUND: While many studies have compared the efficacy of Pap cytology, visual inspection with acetic acid (VIA) and human papillomavirus (HPV) DNA assays for the detection cervical intraepithelial neoplasia and cancer, few have evaluated the program effectiveness. METHODS AND FINDINGS: A population-based sample of 5603 women from Medchal Mandal in Andhra Pradesh, India were invited to participate in a study comparing Pap cytology, VIA, and HPV DNA screening for the detection of CIN3+. Participation in primary screening and all subsequent follow-up visits was rigorously tracked. A 20% random sample of all women screened, in addition to all women with a positive screening test result underwent colposcopy with directed biopsy for final diagnosis. Sensitivity, specificity, positive and negative predictive values were adjusted for verification bias. HPV testing had a higher sensitivity (100%) and specificity (90.6%) compared to Pap cytology (sensitivity  =  78.2%; specificity = 86.0%) and VIA (sensitivity = 31.6%; specificity = 87.5%). Since 58% of the sample refused involvement and another 28% refused colposcopy or biopsy, we estimated that potentially 87.6% of the total underlying cases of CIN3 and cancer may have been missed due to program failures. CONCLUSIONS: We conclude that despite our use of available resources, infrastructure, and guidelines for cervical cancer screening implementation in resource limited areas, community participation and non-compliance remain the major obstacles to successful reduction in cervical cancer mortality in this Indian population. HPV DNA testing was both more sensitive and specific than Pap cytology and VIA. The use of a less invasive and more user-friendly primary screening strategy (such as self-collected swabs for HPV DNA testing) may be required to achieve the coverage necessary for effective reduction in cervical cancer mortality

Planning for resilience in screening operations using discrete event simulation modeling: example of HPV testing in Peru

ABSTRACT: Background: The World Health Organization (WHO) has called for the elimination of cervical cancer. Unfortunately, the implementation of cost-effective prevention and control strategies has faced significant barriers, such as insufficient guidance on best practices for resource and operations planning. Therefore, we demonstrate the value of discrete event simulation (DES) in implementation science research and practice, particularly to support the programmatic and operational planning for sustainable and resilient delivery of healthcare interventions. Our specific example shows how DES models can inform planning for scale-up and resilient operations of a new HPV-based screen and treat program in Iquitos, an Amazonian city of Peru. Methods: Using data from a time and motion study and cervical cancer screening registry from Iquitos, Peru, we developed a DES model to conduct virtual experimentation with “what-if” scenarios that compare different workflow and processing strategies under resource constraints and disruptions to the screening system. Results: Our simulations show how much the screening system’s capacity can be increased at current resource levels, how much variability in service times can be tolerated, and the extent of resilience to disruptions such as curtailed resources. The simulations also identify the resources that would be required to scale up for larger target populations or increased resilience to disruptions, illustrating the key tradeoff between resilience and efficiency. Thus, our results demonstrate how DES models can inform specific resourcing decisions but can also highlight important tradeoffs and suggest general “rules” for resource and operational planning. Conclusions: Multilevel planning and implementation challenges are not unique to sustainable adoption of cervical cancer screening programs but represent common barriers to the successful scale-up of many preventative health interventions worldwide. DES represents a broadly applicable tool to address complex implementation challenges identified at the national, regional, and local levels across settings and health interventions—how to make effective and efficient operational and resourcing decisions to support program adaptation to local constraints and demands so that they are resilient to changing demands and more likely to be maintained with fidelity over time

Rates of New Human Papillomavirus Detection and Loss of Detection in Middle-aged Women by Recent and Past Sexual Behavior.

BACKGROUND: Understanding the source of newly detected human papillomavirus (HPV) in middle-aged women is important to inform preventive strategies, such as screening and HPV vaccination. METHODS: We conducted a prospective cohort study in Baltimore, Maryland. Women aged 35-60 years underwent HPV testing and completed health and sexual behavior questionnaires every 6 months over a 2-year period. New detection/loss of detection rates were calculated and adjusted hazard ratios were used to identify risk factors for new detection. RESULTS: The new and loss of detection analyses included 731 women, and 104 positive for high-risk HPV. The rate of new high-risk HPV detection was 5.0 per 1000 woman-months. Reporting a new sex partner was associated with higher detection rates (adjusted hazard ratio, 8.1; 95% confidence interval, 3.5-18.6), but accounted only for 19.4% of all new detections. Among monogamous and sexually abstinent women, new detection was higher in women reporting ?5 lifetime sexual partners than in those reporting <5 (adjusted hazard ratio, 2.2; 95% confidence interval, 1.2-4.2). CONCLUSION: Although women remain at risk of HPV acquisition from new sex partners as they age, our results suggest that most new detections in middle-aged women reflect recurrence of previously acquired HPV

Whole tissue cervical mapping of HPV infection: Molecular evidence for focal latent HPV infection in humans.

In this study, we aimed to provide molecular evidence of HPV latency in humans and discuss potential challenges of conducting studies on latency. We analyzed the entire cervix of two women who underwent hysterectomy unrelated to cervical abnormality. The cervices were sectioned into 242 and 186 sets respectively, and each set was tested separately for HPV using the SPF10-PCR-DEIA-LiPA25 system. To identify whether there was any evidence of transforming or productive infection, we used the biomarkers E4 and P16INK4a to stain slides immediately adjacent to HPV-positive sections. HPV was detected in both cervices. In patient 1, 1/242 sets was positive for HPV31. In patient 2, 13/186 sets were positive for HPV18 and 1/186 was positive for HPV53. The infection was very focal in both patients, and there was no sign of a transforming or productive infection, as evaluated by the markers E4 and P16INK4a. Had we only analyzed one set from each block, the probability of detecting the infection would have been 32.3% and 2%, respectively.Our findings support the idea that HPV may be able to establish latency in the human cervix; however, the risk associated with a latent HPV infection remains unclear