Natural History Of Human Papillomavirus Infection Research Articles

Adding a quadrivalent human papillomavirus vaccine to the UK cervical cancer screening programme: A cost-effectiveness analysis.

BackgroundWe assessed the cost-effectiveness of adding a quadrivalent (6/11/16/18) human papillomavirus (HPV) vaccine to the current screening programme in the UK compared to screening alone.MethodsA Markov model of the natural history of HPV infection incorporating screening and vaccination was developed. A vaccine that prevents 98% of HPV 6, 11, 16 and 18-associated disease, with a lifetime duration and 85% coverage, in conjunction with current screening was considered.ResultsVaccination with screening, compared to screening alone, was associated with an incremental cost-effectiveness ratio of £21,059 per quality adjusted life year (QALY) and £34,687 per life year saved (LYS). More than 400 cases of cervical cancer, 6700 cases of cervical intraepithelial neoplasia and 4750 cases of genital warts could be avoided per 100,000 vaccinated girls. Results were sensitive to assumptions about the need for a booster, the duration of vaccine efficacy and discount rate.ConclusionThese analyses suggest that adding a quadrivalent HPV vaccine to current screening in the UK could be a cost-effective method for further reducing the burden of cervical cancer.

Cost-effectiveness analysis of the introduction of a quadrivalent human papillomavirus vaccine in France

A vaccine to prevent diseases due to human papillomavirus (HPV) types 6, 11, 16, and 18 is now available in France. The objective of this study was to assess the health and economic impact in France of implementing a quadrivalent HPV vaccine alongside existing screening practices versus screening alone. A Markov model of the natural history of HPV infection incorporating screening and vaccination, was adapted to the French context. A vaccine that would prevent 100 percent of HPV 6, 11, 16, and 18-associated diseases, with lifetime duration and 80 percent coverage, given to girls at age 14 in conjunction with current screening was compared with screening alone. Results were analyzed from both a direct healthcare cost perspective (DCP) and a third-party payer perspective (TPP). Indirect costs such as productivity loss were not taken into account in this analysis. The incremental cost per life-year gained from vaccination was euro12,429 (TPP) and euro20,455 (DCP). The incremental cost per quality-adjusted life-year (QALY) for the introduction of HPV vaccination alongside the French cervical cancer screening program was euro8,408 (TPP) and euro13,809 (DCP). Sensitivity analyses demonstrated that cost-effectiveness was stable, but was most sensitive to the discount rate used for costs and benefits. Considering the commonly accepted threshold of euro50,000 per QALY, these analyses support the fact that adding a quadrivalent HPV vaccine to the current screening program in France is a cost-effective strategy for reducing the burden of cervical cancer, precancerous lesions, and genital warts caused by HPV types 6, 11, 16, and 18.

Molecular basis of cervical carcinogenesis by high-risk human papillomaviruses

Over the last two decades since discovery of human papillomavirus (HPV) type 16 and 18 DNAs in cervical cancers by Dr. Harald zur Hausen, HPVs have been well characterized as causative agents for cervical cancer. Viral DNA from a specific group of HPVs can be detected in at least 90% of all cervical cancers and two viral genes, E6 and E7, are invariably expressed in HPV-positive cervical cancer cells. Their gene products are known to inactivate the major tumor suppressors, p53 and pRB, respectively. In addition, one function of E6 is to activate telomerase, and E6 and E7 cooperate to effectively immortalize human primary epithelial cells. Though expression of E6 and E7 is itself not sufficient for cancer development, it seems to be either directly or indirectly involved in every stage of multi-step carcinogenesis. Indeed, it has been shown that only one or two genetic alterations in addition to expression of E6 and E7 are experimentally sufficient to confer tumorigenicity to normal human cervical keratinocytes. Epidemiological and biological studies suggest the potential efficacy of prophylactic vaccines to prevent genital HPV infection as an anti-cancer strategy. However, given the widespread nature of HPV infection and unresolved issues about the duration and type specificity of the currently available HPV vaccines, it is crucial that molecular details of the natural history of HPV infection as well as the biological activities of the viral oncoproteins be elucidated in order to provide the basis for development of new therapeutic strategies against HPV-associated malignancies. This review highlights the novel functions of E6 and E7 as well as the molecular mechanisms of HPV-induced carcinogenesis.

Análisis de coste-efectividad de la vacunación frente al virus del papiloma humano tipos 6, 11, 16 y 18 en España

ObjectivesA vaccine to prevent diseases due to human papillomavirus (HPV) types 6, 11, 16 and 18 is now available in Spain. The objective of this study was to assess the health and economic impact in Spain of implementing a four-valent HPV vaccine alongside existing screening versus screening alone. MethodsA Markov model of the natural history of HPV infection, incorporating screening and vaccination, was adapted to the Spanish context. A vaccine that would prevent 100% of HPV 6, 11, 16 and 18-associated diseases, with a lifetime duration and 80% coverage, given to girls at age 11 plus current screening was compared to screening alone. The analysis was made from the third-party payer perspective and therefore excluded indirect costs such as loss of productivity. ResultsThe incremental cost per life years gained (LYG) and per quality-adjusted life years (QALY) gained for the introduction of HPV vaccination alongside the Spanish cervical cancer screening programme was 8,657 € and 6,493 €, respectively. Sensitivity analyses demonstrated that the cost-effectiveness was stable, but was most sensitive to the discount rate used for costs and benefits. ConclusionsThese analyses demonstrate that adding a four-valent HPV vaccine to the current screening programme in Spain is a cost-effective strategy for reducing the burden of cervical cancer, pre-cancerous lesions and genital warts.

Vaccine Policy Analyses Can Benefit from Natural History Studies of Human Papillomavirus in Men

With the licensure of the human papillomavirus (HPV) vaccine in the United States and many other countries, an understanding of the natural history of HPV infection is imperative for establishment of appropriate policies and guidelines for its use. Although our knowledge of the natural history of HPV infection in

Estimating the number needed to vaccinate to prevent diseases and death related to human papillomavirus infection

A vaccine against human papillomavirus (HPV) types 6, 11, 16 and 18 is now licensed for use in Canada and many other countries. We sought to estimate the number needed to vaccinate to prevent HPV-related diseases and death. A cohort model of the natural history of HPV infection was developed. Model simulations were based on 209 different parameter sets that reproduced Canadian HPV type-specific data for infection, cervical intraepithelial neoplasia, cervical cancer and genital warts. The number needed to vaccinate was calculated as the number of women who would need to be vaccinated to prevent an HPV-related event during their lifetime. Among 12-year-old girls, we estimated that the number needed to vaccinate to prevent an episode of genital warts would be 8 (80% credibility interval [CrI] 5-15) and a case of cervical cancer 324 (80% CrI 195-757). These estimates were based on the assumption that the vaccine procures lifelong protection and that its efficacy is 95%. If vaccine protection is assumed to wane at 3% per year, the predicted number needed to vaccinate would increase to 14 (80% CrI 6-18) and 9080 (80% CrI 1040-does not prevent), respectively. The latter number would be greatly reduced with the addition of a booster dose, to 480 (80% CrI 254-1572). Our model predictions suggest that vaccination with the currently available HPV vaccine may significantly reduce the incidence of genital warts, cervical intraepithelial neoplasia and cervical cancer. However, the benefits (particularly in terms of cervical cancer reduction) are highly dependent on the duration of vaccine protection, on which evidence is currently limited.

Human papillomavirus, pregnancy and HIV infection

Evaluation of: Minkoff H, Xian LS, Watts HD et al. Relationship of pregnancy to human papillomavirus among human immunodeficiency virus-infected women. Obstet. Gynecol. 108[4], 953–960 [2006].The relationships that exist between human papillomavirus (HPV) infection and pregnancy remain controversial and have rarely been properly investigated in the context of HIV infection. The paper under discussion presents important data on the effect of pregnancy on the natural history of HPV infection obtained from two US cohorts of HIV-infected women, who were either pregnant at enrollment or became pregnant during follow-up. The results indicate that cervical HPV prevalence and HPV DNA viral loads are not increased during pregnancy in HIV-infected women and that incident HPV detection is significantly lower during pregnancy when compared with the postpregnancy period. These results suggest that the immune suppression and changes in vaginal milieu associated with pregnancy are of little importance compared with immu...

Human papillomavirus genital infection in modern gynecology: genetic and genomic aspects

HPV (human papillomavirus) is a virus responsible for many female and male genital tract diseases. It is a small nonenveloped virus with icosahedral symmetry that contains a double-stranded DNA genomes of approximately 7,900 bp. Approximately 200 different HPVs have been characterized, classified in mucosal and cutaneous viruses, responsible for a wide spectrum of clinical conditions, from simple feet and hands warts to genital cancer. Their genome is functionally distinct in three regions. The condition of the host immune system is one of the factors that can strongly influence the natural history of HPV infection. The primary response to viral infection is cell-mediated, so conditions that compromise the immune system increase the viral infection risk. The molecular mechanisms involved in the onset of the cervical carcinoma are well defined, and they are mainly associated to the ability of the proteins E6 and E7 to neutralize the activity of p53 and retinoblastoma protein, respectively. The infection of HPV is mainly diagnosed through molecular methods. Several assays have been developed for the simultaneous identification of HPV types, the majority of which are polymerase chain reaction-based assays. Side by side with these assays, the emerging technology of the DNA chip may offer a reliable diagnostic tool for discriminating easily between many HPV genotypes.

A cost-effectiveness analysis of adding a human papillomavirus vaccine to the Australian National Cervical Cancer Screening Program

The cost-effectiveness of adding a human papillomavirus (HPV) vaccine to the Australian National Cervical Screening Program compared to screening alone was examined. A Markov model of the natural history of HPV infection that incorporates screening and vaccination was developed. A vaccine that prevents 100% of HPV 16/18-associated disease, with a lifetime duration of efficacy and 80% coverage offered through a school program to girls aged 12 years, in conjunction with current screening was compared with screening alone using cost (in Australian dollars) per life-year (LY) saved and quality-adjusted life-year (QALY) saved. Sensitivity analyses included determining the cost-effectiveness of offering a catch-up vaccination program to 14-26-year-olds and accounting for the benefits of herd immunity. Vaccination with screening compared with screening alone was associated with an incremental cost-effectiveness ratio (ICER) of $51 103 per LY and $18 735 per QALY, assuming a cost per vaccine dose of $115. Results were sensitive to assumptions about the duration of vaccine efficacy, including the need for a booster ($68 158 per LY and $24 988 per QALY) to produce lifetime immunity. Accounting for herd immunity resulted in a more attractive ICER ($36 343 per LY and $13 316 per QALY) for girls only. The cost per LY of vaccinating boys and girls was $92 052 and the cost per QALY was $33 644. The cost per LY of implementing a catch-up vaccination program ranged from $45 652 ($16 727 per QALY) for extending vaccination to 14-year-olds to $78 702 ($34 536 per QALY) for 26-year-olds. These results suggest that adding an HPV vaccine to Australia's current screening regimen is a potentially cost-effective way to reduce cervical cancer and the clinical interventions that are currently associated with its prevention via screening alone.

Serum antibody response to Human papillomavirus (HPV) infections detected by a novel ELISA technique based on denatured recombinant HPV16 L1, L2, E4, E6 and E7 proteins

BackgroundHuman papillomaviruses (HPVs) are the primary etiological agents of cervical cancer and are also involved in the development of other tumours (skin, head and neck). Serological survey of the HPV infections is important to better elucidate their natural history and to disclose antigen determinants useful for vaccine development. At present, the analysis of the HPV-specific antibodies has not diagnostic value for the viral infections, and new approaches are needed to correlate the antibody response to the disease outcome. The aim of this study is to develop a novel ELISA, based on five denatured recombinant HPV16 proteins, to be used for detection HPV-specific antibodies.MethodsThe HPV16 L1, L2, E4, E6 and E7 genes were cloned in a prokaryotic expression vector and expressed as histidine-tagged proteins. These proteins, in a denatured form, were used in ELISA as coating antigens. Human sera were collected from women with abnormal PAP smear enrolled during an ongoing multicenter HPV-PathogenISS study in Italy, assessing the HPV-related pathogenetic mechanisms of progression of cervical cancer precursor lesions. Negative human sera were collected from patients affected by other infectious agents. All the HPV-positive sera were also subjected to an avidity test to assess the binding strength in the antigen-antibody complexes.ResultsMost of the sera showed a positive reactivity to the denatured HPV16 proteins: 82% of the sera from HPV16 infected women and 89% of the sera from women infected by other HPV genotypes recognised at least one of the HPV16 proteins. The percentages of samples showing reactivity to L1, L2 and E7 were similar, but only a few serum samples reacted to E6 and E4. Most sera bound the antigens with medium and high avidity index, suggesting specific antigen-antibody reactions.ConclusionThis novel ELISA, based on multiple denatured HPV16 antigens, is able to detect antibodies in women infected by HPV16 and it is not genotype-specific, as it detects antibodies also in women infected by other genital HPVs. The assay is easy to perform and has low cost, making it suitable for monitoring the natural history of HPV infections as well as for detecting pre-existing HPV antibodies in women who receive VLP-based HPV vaccination.

PL7 Oral viral infections that could be transmitted oro‐genitally

Orogenital transmission has been suggested for several viruses, e.g. herpes simplex virus‐1 and ‐2 (HS‐1 and HSV‐2), Epstein‐Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus‐8 (HHV‐8), human papillomavirus (HPV) and HIV. Most studies have focused on HIV, HSV and HPV. Unprotected orogenital contact, especially receptive oral intercourse, is associated with greater risk of HIV transmission than previously thought. Factors potentially associated with increased risk of HIV transmission through oral sex include poor oral health, the salivary anti‐HIV properties such as peroxidases and thrombospondin‐1, the local and systemic immunological responses, concomitant sexually transmitted infections, ejaculation in the mouth, local mucosal integrity, and the level of infectious HIV present at the oral mucosa. The probability of per act transmission in oral intercourse with ejaculation is 0.04%. HSV‐2 has been regarded as a sexually transmitted virus while HSV‐1 is causing primary herpetic gingivo‐stomatitis, muco‐cutaneous oro‐facial disease and ocular disease. Also HSV‐2 might be detected occasionally in oro‐facial area. Recent data on young women with a primary genital infection indicate that HSV‐1 is much more frequent than HSV‐2. Oro‐genital route of transmission is more common than expected in genital HSV‐1 infections. EBV is a tumorigenic herpes virus that is carried as a persistent infection by more than 90% of adults. Most persistently infected people produce EBV in their saliva, and transmission is through close contact. There is a significant association between sexual intercourse and EBV seropositivity, increasing with numbers of sex partners. Because EBV has been found in genital secretions from healthy seropositive men and women, direct spread of virus during sexual intercourse is possible. Today, 106 HPV types have been sequenced of which almost 40 have been detected also in oral mucosa, causing benign epithelial lesions (papillomas, condylomas, warts and focal epithelial hyperplasia, or FEH). Recent meta‐analyses of the case‐control studies have confirmed HPV as an independent risk factor for oral SCC with odds ratios (OR) 3.7 to 5.4. HPV16 is the overwhelmingly most frequent type. HPV has been regarded as a sexually transmitted disease but this view is challenged by frequent detection of HPV in children. Unlike in genital tract, natural history of oral HPV infection is poorly studied. As part of the Finnish HPV Family Study we evaluated natural history of oral HPV in within family members. The detection rate of HR HPVs varied from 15% to 27%. Our results indicate that natural history of HPV infection in oral mucosa mimics that of genital HPV infections. Oral sex had no association to oral HPV infection, but a persistent oral HPV infection of the spouse increased the risk of persistent oral HPV infection in the other spouse 10‐fold.

PL8 The causal role of genital human papillomavirus (hpv) infections in cervical carcinogenesis

Well over 150 different human papillomavirus (HPV) types are currently recognised, divided according to their preferential targets into (i) cutaneous and (ii) mucosal HPV types. The latter are further classified as low‐risk (HPV 6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, and CP6108), intermediate risk (HPV 26, 53, and 66) and high‐risk (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82) types, according to their association with malignant lesions at genital‐ and extra‐genital mucosal sites. Since the recognition of their close association with cervical cancer precursor (CIN) lesions in 1976, HPVs have emerged as the most important human tumour viruses. Beyond any doubt, oncogenic HPV types are the single most important etiological agents of cervical cancer (CC) and CIN lesions, whereas low‐risk HPV types are associated with benign mucosal squamous cell lesions (papillomas and condylomas). Apart from extensive epidemiological documentation, the link between HPV and CC has been confirmed by molecular biological research and prospective cohort studies disclosing the natural history of HPV infections and the true precancer nature of high‐grade CIN lesions. The latter develop as a result of persistent oncogenic HPV infections, known to predispose the women to significantly increased risk of CC. Factors predicting both the disease outcome (persistence, progression, regression) and the viral events (incident infections, HPV persistence, virus clearance) are emerging only recently. In addition to testing the feasibility of various optional screening tools in early detection of CC precursors, as well as to ongoing clinical trials with prophylactic HPV vaccines, another major focus of current HPV research includes the intense screening of new biomarkers as potential predictors of disease progression and outcome of oncogenic HPV infections.

Chapter 29: Knowledge gaps and priorities for research on prevention of HPV infection and cervical cancer

The recognition that human papillomavirus (HPV) infection is the necessary cause of cervical cancer brought new prevention paradigms in screening and HPV immunization. We now face many questions about how to implement an ambitious evidence-based agenda for cervical cancer prevention. Much is known about the epidemiology and natural history of HPV infection but several key variables remain to be elucidated. Research on HPV transmission requires new study designs to provide useful insights into preventive strategies. HPV testing has carved a niche in clinical practice but to consolidate its role in screening still requires evidence of long-term benefit. The rapidly evolving field of HPV diagnostics has contributed useful information concerning the value of HPV typing. Other screening methods hold promise in specific settings. The decade-long process that brought HPV vaccines to the doorstep of public health application is over. Many questions remain concerning long-term efficacy, correlates of protection, age of vaccination, and delivery. As vaccination makes inroads as a cancer control strategy, screening practices must be reformulated to maximize the synergy between primary and secondary prevention. Research on how to achieve an efficient combination of these modalities is yet to begin, but mathematical models have provided a useful road map for field-testing of promising algorithms. Daunting questions loom large concerning delivery of vaccines to those populations that need it the most. The field of HPV and cervical cancer prevention has never been so multi-disciplinary. A new era has begun and the challenges are many.

The development of cervical cancer and its precursors: what is the role of human papillomavirus infection?

Human papillomavirus (HPV) is a significant health care burden in the United States. The majority of sexually active men and women will be infected with HPV at some point in their lives and are subject to developing human papillomavirus-associated disease. Current estimates suggest that 20 million Americans are currently infected, and more than 5 million new infections occur each year. The prevalence of human papillomavirus is highest in populations in their late teens and early twenties, with nearly half of all new human papillomavirus infections occurring within 3 years of first intercourse. HPV is the necessary cause of genital warts, cervical intraepithelial neoplasia, and invasive cervical cancer. As such, human papillomavirus is responsible for significant medical morbidity and health care costs. Screening with cervical cytology has significantly reduced mortality rates; however, approximately 3900 women will die in 2005 from cervical cancer in the United States. Human papillomavirus DNA testing has shown promise in identifying high-grade abnormalities as an adjunct to traditional cytology, and should be used according to guidelines established by the American Cancer Society and the American College of Obstetricians and Gynecologists. The epidemiology of HPV infection and a brief introduction to the natural history of HPV infection will be presented here.

Human papillomavirus infection in Rio de Janeiro, Brazil: a retrospective study

There is considerable data to support a central role for human papillomavirus (HPV) in the etiology of cervical cancer. More than a 100 HPV types have been described, and 40 have been isolated from benign and malignant genital lesions. Consequently, there is strong motivation to evaluate HPV testing for cervical cancer screening. Few studies concerning the natural history of HPV infection have been conducted in the state of Rio de Janeiro. We determined the prevalence of HPV types in female genital lesions by using Hybrid Capture Assay (HCA) and we retrospectively analyzed the course of HPV infection. Our sample included 788 women attended at Laboratórios Sérgio Franco. The average age of the participants was 29.6 years. HPV prevalence and cytological diagnosis were determined. The overall prevalence of HPV DNA in the study group was 50.1% (395/788), ranging from 25% (NORMAL) to 100% in high-grade intraepithelial lesions (HSIL). High risk HPV was found in 12% inflammatory, 58.3% HPV, 63.2% LSIL and 100% HSIL. A retrospective analysis of 78 patients showed that 22 presented persistent lesions, 2 had progressive lesions, 4 had regressive lesions, 13 showed latent infections, 18 were transiently infected and 19 were submitted to curative treatment. No cases of cancer were registered in this population, which can afford private medical care and regular follow-up exams. We suggest that HCA be used in specific cases involving persistent and recurrent lesions.

The epidemiology of human papillomavirus infections

Infection with oncogenic human papillomavirus (HPV) types is a necessary cause of cervical cancer, the second most frequently occurring cancer in women worldwide. Rates of acquisition of HPV are high, particularly among sexually active young adults. Reported estimates of incident HPV infection among initially negative women have reached as high as 60% over a 5-year follow-up period. In this article, we review the epidemiology of HPV infection. In addition to estimates of disease frequency, we highlight risk factors for HPV infection, including the number of lifetime sex partners, which is the most salient risk factor. We discuss significant issues surrounding the natural history of HPV infection, including viral persistence versus clearance, immune response, development of lesions and development of cancer. Finally, we discuss strategies for preventing HPV infection.

Beyond Human Papillomavirus: The Cervix, Exogenous Secondary Factors, and the Development of Cervical Precancer and Cancer

Human papillomavirus (HPV) is the necessary but probably not sufficient cause of cervical precancer and cancer. Secondary exogenous and endogenous factors, HPV cofactors, may contribute to the probability of a cancer-associated (oncogenic) HPV infection progressing to cervical precancer and cancer. For these cofactors to influence the natural history of HPV infection, they must act on cervical tissue to promote viral persistence, progression to precancer or cancer given viral persistence, or both. The aim of this review was to examine briefly the impact these factors may have on carcinogenesis of the cervix. Specifically, the roles of the cervical transformation zone, cervical immunity, inflammation and coinfection, and exposure to the main HPV cofactors (smoking, oral contraceptive use, and multiparity) are discussed.

Relationship between smoking and human papillomavirus infections in HIV-infected and -uninfected women.

Background. Smoking may increase the risk of cervical cancer, a disease that is related to human papillomavirus (HPV) infection. However, the effects of smoking on the natural history of HPV are poorly understood, especially in women coinfected with human immunodeficiency virus (HIV).Methods. HIV-infected (n=1797) and HIV-uninfected (n=496) women were assessed every 6 months for type-specific HPV DNA. Smoking status was self-reported. Covariates included age, parity, sexual behavior, HIV load, CD4(+) T cell count, and antiretroviral therapy.Results. Smoking was positively associated with HPV prevalence at baseline in HIV-infected women (P=.002) and was significantly associated with type-specific HPV detection (e.g., type 18, odds ratio [OR], 2.45; 95% confidence interval [CI], 1.86-3.22). In Cox models, detection of HPV was significantly associated with smoking in HIV-infected women (relative hazard [RH], 1.33; 95% CI, 1.10-1.60; P=.003), but HPV persistence was not (RH, 0.97; 95% CI, 80-1.16; P=.72). The overall likelihood of acquiring persistent HPV was higher in smokers (OR, 1.39; 95% CI, 1.05-1.86; P=.023) because of greater incidence.Conclusions. Among HIV-infected women, smoking is associated with a significantly higher prevalence and incidence of HPV infection. Smoking during HIV infection may alter the natural history of HPV infection and increase the risk of cervical disease.

Projected clinical benefits and cost-effectiveness of a human papillomavirus 16/18 vaccine.

Human papillomavirus (HPV) vaccine may be commercially available in a few years. We explored the clinical benefits and cost-effectiveness of introducing an HPV16/18 vaccine in a population with an organized cervical cancer screening program. A computer-based model of the natural history of HPV and cervical cancer was used to project cancer incidence and mortality, life expectancy (adjusted and unadjusted for quality of life), lifetime costs, and incremental cost-effectiveness ratios (i.e., the additional cost of a strategy divided by its additional clinical benefit compared with the next most expensive strategy) associated with different cancer prevention policies, including vaccination (initiated at age 12 years), cytologic screening (initiated at 18, 21, 25, 30, or 35 years), and combined vaccination and screening strategies. We assumed that vaccination was 90% effective in reducing the risk of persistent HPV16/18 infections and evaluated alternative assumptions about vaccine efficacy, waning immunity, and risk of replacement with non-16/18 HPV types. Our model showed that the most effective strategy with an incremental cost-effectiveness ratio of less than 60 dollars-000 per quality-adjusted life year is one combining vaccination at age 12 years with triennial conventional cytologic screening beginning at age 25 years, compared with the next best strategy of vaccination and cytologic screening every 5 years beginning at age 21 years. This triennial strategy would reduce the absolute lifetime risk of cervical cancer by 94% compared with no intervention. These results were sensitive to alternative assumptions about the underlying patterns of cervical cancer screening, duration of vaccine efficacy, and natural history of HPV infection in older women. Our model predicts that a vaccine that prevents persistent HPV16/18 infection will reduce the incidence of HPV16/18-associated cervical cancer, even in a setting of cytologic screening. A program of vaccination that permits a later age of screening initiation and a less frequent screening interval is likely to be a cost-effective use of health care resources.

High prevalence of anal squamous intraepithelial lesions in HIV-positive men despite the use of highly active antiretroviral therapy.

The impact of highly active antiretroviral therapy (HAART) on the natural history of HPV infection and anal squamous intraepithelial lesions (SIL) in HIV-infected men who have sex with men (MSM) is poorly documented. GOAL The goal of this study was to evaluate the prevalence of anal HPV infection and SIL inpatients under HAART. Forty-five HIV-infected protease inhibitor-experienced MSM were enrolled in a cross-sectional study. Each patient provided anal samples for anal cytology, histology, and human papillomavirus (HPV) DNA testing. The patients had previously received HAART for a median of 32 months. Anal cytology was abnormal in 32 of 45 (71%) patients, including high-grade SIL in 10 patients (22%), low-grade SIL in 19 patients (42%), and atypical squamous cells of undetermined significance in 3 patients (7%). HPV DNA was detected 36/45 men (80%). The prevalence of anal SIL and HPV infection were similar in patients exhibiting a significant increase in CD4+ cell count after HAART initiation compared with those who did not. Our results demonstrate a high prevalence of anal SIL, including high-grade SIL, and anal HPV infection in HIV-infected MSM despite immune restoration under HAART.