Carcinogenic Human Papillomavirus Research Articles

Prevalence of Human Papillomavirus (HPV) and HPV Type Distribution in Penile Samples in Young Men in Denmark: Results 10 Years After Implementation of a Girls-Only HPV Vaccination Program.

In Denmark, a girls-only human papillomavirus (HPV) vaccination program was initiated in 2008-2009. The study aim was to assess the HPV prevalence and type distribution in younger men prior to HPV vaccination in men. The study population was younger men who attended information days regarding military service. At random days (2019-2020), 280 men were included. We collected questionnaire data regarding risk factors for HPV infection and a penile swab for HPV testing. We compared results in this study with those from a previous study of young men (2006-2007). The majority of participants (94%) were 18-20 years old. The median number of lifetime sexual partners was 4. Altogether, 130 men (46.4%) were HPV positive. No infections with HPV types 6, 11, 16, 18, 31, and 45 were detected. The most frequent type was HPV-51 (detected in 11.1%). Comparison showed that the odds of high-risk HPV type infection were higher in 2019-2020 (prevalence odds ratio [POR], 1.7 [95% confidence interval {CI}, 1.1-2.7]) compared with 2006-2007. In contrast, the odds were lower (POR, 0.3 [95% CI, .1-.6]) for HPV types targeted by the 9-valent HPV vaccine. The multicohort girls-only vaccination program has to a large degree protected young men against the HPV types included in the licensed vaccines. This does not speak against gender-neutral vaccination as the HPV prevalence is still high, although consisting largely of less carcinogenic HPV types.

High-risk human papillomaviruses l1 gene isolates identified in Western Kazakhstan

Kazakhstani researchers reported a significant prevalence of highly carcinogenic human papillomavirus types in the country.<br /> The article <b>aimed</b> to present HPV L1 gene sequencing developments in women affected with cervical cancer throughout the western part of Kazakhstan with provided findings on the geographic pathways of obtained isolates.<br /> <b>Methods. </b>The HPV L1 gene was amplified using the consensus primers MY09HPV 5’-CGTCCMARRGGAWACTGATC-3’ and MY11HPV 5’ – GCMCAGGGWCATAAYAATGG-3’.  The purified DNA was used as the target for direct nucleotide sequencing. Phylogenetic analyses were conducted using the MegAlign program from the LASERGENE software package (version 6.0; DNA star, Madison, WI) and with MEGA version 5.0 software. A multiple alignment was created through Clustal W software, and the neighbor-joining method was used to construct the phylogenetic tree.<br /> <b>Results.</b> Of 70 HPV samples transported to the Astana shared laboratory for gene L1 sequencing, only ten appeared fit to obtain isolates (14.3%). The viral load of the samples ranged from 3.3 to 8.2, and the range of DNA concentration was from 8.16 to 69.6 ng/uL. HPV16 unique Kazakhstani isolate from Aktobe, having its own branch, and not yet registered in the world genebank, was revealed. An isolate of potentially carcinogenic HPV53 forming a remote cluster with KF436822/1, KU951264.1 - Southwest China, and 97% identity with EU056643.1 - Ireland, and acted as a single agent for invasive cervical cancer was identified.<br /> In general, the sequencing findings indicate the variety of ways for HPV pervasion into the western region of Kazakhstan: North and South America, Europe, and Asia.<br /> <i><i>The study was recorded in the ISRCTN registry, No. 7154910, 02/01/2018.</i></i>

Predictive Value of Various Atypical Cells for the Detection of Human Papillomavirus in Cervical Smears.

It is thought that numerous genotypes of human papillomavirus (HPV) are associated with various atypical cells, such as multinucleated cells, koilocytes, binucleated cells, parakeratotic cells, and giant cells, in the cervix. We previously showed the specificity of HPV genotypes for koilocytes and multinucleated cells. Therefore, in this study, we analyzed the association among HPV genotypes and binucleated cells, parakeratotic cells, and giant cells in Papanicolaou (Pap) smears. We detected HPV genotypes and atypical cells in 651 cases of liquid-based cytology with an abnormal Pap smear. The HPV genotypes associated with atypical cells were evaluated using stepwise logistic regression with backward elimination and a likelihood ratio test for model construction. Polymerase chain reaction was used to determine the HPV genotypes in whole liquid-based cytology samples and microdissected cell samples from Pap smear slides. Binucleated cells were significantly associated with HPV genotype 42. Moreover, parakeratotic cells were significantly associated with certain HPV genotypes, such as HPV40. However, it was difficult to detect specific HPV genotypes by the manual microdissection-polymerase chain reaction method despite the presence of binucleated cells and parakeratotic cells. Thus, the presence of binucleated cells, parakeratotic cells, and giant cells in Pap smears may not be predictive of cervical lesions above low-grade squamous intraepithelial lesions or infection with highly carcinogenic HPV genotypes.

Diversity in Proprotein Convertase Reactivity among Human Papillomavirus Types.

The cleavage of viral surface proteins by furin is associated with some viruses' high virulence and infectivity. The human papillomavirus (HPV) requires the proteolytic processing of its capsid proteins for activation before entry. Variability in reactivity with furin and other proprotein convertases (PCs) among HPV types was investigated. HPV16, the most prevalent and carcinogenic HPV type, reacted with PCs with the broadest selectivity compared to other types in reactions of pseudoviral particles with the recombinant PCs, furin, PC4, PC5, PACE4, and PC7. Proteolytic preactivation was assessed using a well-established entry assay into PC-inhibited cells based on the green fluorescent protein as a reporter. The inhibition of the target cell PC activity with serpin-based PC-selective inhibitors also showed a diversity of PC selectivity among HPV types. HPV16 reacted with furin at the highest rate compared to the other types in time-dependent preactivation reactions and produced the highest entry values standardized to pseudoviral particle concentration. The predominant expression of furin in keratinocytes and the high reactivity of HPV16 with this enzyme highlight the importance of selectively targeting furin as a potential antiviral therapeutic approach.

Cervical Cancer Screening: A Review

(Abstracted from JAMA 2023;330(6):547–558) More than 90% of cervical cancer is caused by persistent infections with carcinogenic human papillomavirus (HPV), leading to precancer and then to cervical cancer. Approximately 100,000 people are treated for cervical precancer, 14,000 people are diagnosed with cervical cancer, and more than 4000 die of cervical cancer in the United States each year.

A novel HPV16 splicing enhancer critical for viral oncogene expression and cell immortalization.

High-risk carcinogenic human papillomaviruses (HPVs), e.g. HPV16, express the E6 and E7 oncogenes from two mRNAs that are generated in a mutually exclusive manner by splicing. The HPV16 E7 mRNA, also known as the E6*I/E7 mRNA, is produced by splicing between splice sites SD226 and SA409, while E6 mRNAs retain the intron between these splice sites. We show that splicing between HPV16 splice sites SD226 and SA409 is controlled by a splicing enhancer consisting of a perfect repeat of an adenosine-rich, 11 nucleotide sequence: AAAAGCAAAGA. Two nucleotide substitutions in both 11 nucleotide sequences specifically inhibited production of the spliced E6*I/E7 mRNA. As a result, production of E7 protein was reduced and the ability of HPV16 to immortalize human primary keratinocytes was abolished. The splicing-enhancing effect was mediated by the cellular TRAP150/THRAP3 protein that also enhanced splicing of other high-risk HPV E6*I/E7 mRNAs, but had no effect on low-risk HPV mRNAs. In summary, we have identified a novel splicing enhancer in the E6 coding region that is specific for high-risk HPVs and that is critically linked to HPV16 carcinogenic properties.

Clinical and morphological features of bladder cancer course in HPV-infected patients

Purpose of the study. To study the histological type, grade of tumor differentiation in patients with primary and recurrent clinically non-muscle-invasive bladder cancer (NMIBC) with highly carcinogenic human papillomavirus (HPV) infection.Patients and methods. Formalin-fixed and paraffin-embedded bladder tumor tissue samples have been studied in 159 patients who underwent transurethral resection (TUR) of the bladder, for the presence of HPV DNA. To detect, quantify and differentiate DNA of HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68 genotypes in the samples, the AmpliSense® HPV HRC genotype-titer-FL was used. The result of the study was taken into account when the amount of DNA of the β-globin gene was at least 1000 copies per reaction. In order to statistically analyze our data we used the Fisher exact test and also calculated the odds ratio (OR) and 95 % CI.Results. According to the results of the study, out of 159 patients, high-risk HPV DNA was detected in the tumor tissue in 59 (37.1 %), of which HPV type 16 was found in 52 patients (89.4 %), HPV 18 was detected in 4 patients type (6.7 %) and type 35 in 3 (5.08 %). In a morphological study of the tissues of HPV-positive patients, the grade of tumor differentiation was G2 in 18 cases (30.5 %), G3 in 37 blocks, and G1 was detected only in 4 cases (6.7 %). In the presence of HPV, the chance of detecting a stage G3 tumor increases by 4.3 times. According to the received data, we can assume that there is a close relationship between detection in HPV patients of high-risk genotypes with moderately differentiated and low-differentiated forms of bladder cancer.Conclusion. this study may indicate that HPV infection affects the grade of tumor differentiation, and this, in turn, may allow the use of the HPV test to assess the nature of the development of relapse and/or progression of the disease.

HPV Testing and its Role in Cervical Cancer Screening.

The recognition that persistent infection with carcinogenic human papillomavirus (HPV) is a necessary cause of cervical precancer and cancer has led to the introduction of HPV testing into cervical cancer screening, either as a primary screening test or in conjunction with cervical cytology (i.e., co-testing). HPV testing has much higher sensitivity for detection of cervical precancer and provides greater long-term reassurance if negative compared to cytology. However, most HPV infections are transient, and do not progress to invasive cancer, thus triage tests are required to identify individuals who should be referred to colposcopy for diagnostic evaluation. This chapter begins with a description of the biology, natural history, and epidemiology of HPV as a foundation for understanding the role of HPV in cervical carcinogenesis. This section is followed by a detailed discussion regarding the introduction of HPV-based testing and triage into cervical cancer screening and management. Summarized triage tests include cervical cytology, HPV genotyping, p16/Ki-67 dual stain, and HPV and cellular methylation markers. The final section of this chapter includes an important discussion on cervical cancer disparities, particularly within the United States, followed by concluding remarks.

Characterization of DoTc2 4510-Identifying HPV16 Presence in a Cervical Carcinoma Cell Line Previously Considered to Be HPV-Negative.

Cervical cancer is the fourth leading cause of cancer deaths in women, with over 340,000 women dying from this disease in 2020. Almost all cases have an underlying persistent infection with an oncogenic high-risk type of human papillomavirus (HPV), mainly HPV16. While cervical squamous cell carcinoma is hardly ever HPV-negative, a small subset of adenocarcinoma exhibits absence of HPV, even after disproval of false-negative testing results due to low viral load. This proportion is evident in many cervical cancer studies and is reflected in the repertoire of model cell lines commonly used in research. As the viral origin of cervical cancer makes it a disease preventable and potentially treatable by immunotherapeutic approaches, it is the focus of many studies. For pertinent research, both a broad set of HPV-infected cervical carcinoma models are required, as well as stringent negative controls. A ubiquitously used HPV-negative cervical adenocarcinoma cell line is C-33A. Another cervical cancer cell line is available for purchase from the American Type Culture Collection (ATCC), namely DoTc2 4510, described to be HPV-negative and thus as a model for a rare gynecological malignancy. Here, we present findings proving that DoTc2 4510 is, in fact, an HPV16-positive cell line. This we assessed using a highly sensitive nested multiplex PCR protocol adapted for the identification of 12 carcinogenic HPV types and a second PCR targeting the HPV16 oncogenes E6 and E7. Subsequently, the protein expression of E6 and E7 was examined, as well as the expression of their target proteins p53, p21, and p16INK4a, to assess E6/E7 functionality. Finally, to attest to the survival dependence of DoTc2 4510 cells on HPV16, we performed an HPV16 E6/E7-targeted siRNA knock-down, which indeed led to senescence induction. Together, these findings demonstrate that DoTc2 4510 is an HPV16-transformed cell line.

Recent Developments in Human Papillomavirus (HPV) Vaccinology.

Human papillomavirus (HPV) is causally associated with 5% of cancers, including cancers of the cervix, penis, vulva, vagina, anus and oropharynx. The most carcinogenic HPV is HPV-16, which dominates the types causing cancer. There is also sufficient evidence that HPV types 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59 cause cervical cancer. The L1 protein, which, when assembled into virus-like particles, induces HPV-type-specific neutralising antibodies, forms the basis of all commercial HPV vaccines. There are six licensed prophylactic HPV vaccines: three bivalent, two quadrivalent and one nonavalent vaccine. The bivalent vaccines protect from HPV types 16 and 18, which are associated with more than 70% of cervical cancers. Prophylactic vaccination targets children before sexual debut, but there are now catch-up campaigns, which have also been shown to be beneficial in reducing HPV infection and disease. HPV vaccination of adults after treatment for cervical lesions or recurrent respiratory papillomatosis has impacted recurrence. Gender-neutral vaccination will improve herd immunity and prevent infection in men and women. HPV vaccines are immunogenic in people living with HIV, but more research is needed on the long-term impact of vaccination and to determine whether further boosters are required.

Age-specific and genotype-specific carcinogenic human papillomavirus prevalence in a country with a high cervical cancer burden: results of a cross-sectional study in Estonia

ObjectivesTo describe age-specific and type-specific carcinogenic human papillomavirus (HPV) prevalence prior to large-scale effect of HPV vaccines in Estonia and to analyse the risk factors associated with carcinogenic HPV.DesignCross-sectional study...

Diagnostic value of high-risk HPV other than type 16/18 in high-grade cervical neoplasia among cytology-negative women: A multicenter retrospective study.

Human papillomavirus (HPV) is a necessary cause of cervical cancer, and a tool more sensitive than cytology for the early screening of cervical precancers. The two most carcinogenic genotypes HPV 16/18 have been reported in the majority of studies. High-risk HPVs other than HPV 16/18 (non-16/18-hrHPVs) cause approximately a quarter of cervical cancers, and we aimed to analyze the genotype-specific prevalence, risk and diagnostic efficiency of non-16/18-hrHPVs in cervical carcinogenesis among Chinese cytology-negative women. A total of 7043 females who had abnormal cervical testing results from January 2018 to October 2021 were enrolled, among them 3091 were cytology-negative. Descriptive statistics was used to estimate the HPV genotype-specific prevalence, and multivariable logistic regression was used to estimate the genotype-specific non-16/18 hrHPVs risk of cervical carcinogenesis. The evaluation of diagnostic value among HPV genotypes included the possibility of predicting cervical intraepithelial neoplasia grade 2/3 or worse (CIN2+/CIN3+) and the diagnostic efficiency measured by increased referral rate and referral numbers of colposcopies per additional CIN2+/CIN3+ detected. Among HPV-positive cytology-negative women, the five dominant genotypes for CIN2+/CIN3+ were HPV 31/33/35/52/58. HPV 52/58/33 had comparatively high sensitivity and specificity in predicting CIN2+/CIN3+, while the referral strategy of multiple HPV58 required 26 colposcopies to detect 1 CIN3+, compared with 14, 12, and 8 required by multiple HPV52, 31, and 33, respectively. HPV31/33/35/52/58 infections are significant risk factors for cervical lesions, and multiple HPV 31/33/52 infections should be included in the previously recommended HPV16/18 genotyping triage for colposcopy in China, as the benefits of disease prevention may outweigh the disadvantages of increasing requirements for colposcopy services.

Prediction of carcinogenic human papillomavirus types in cervical cancer from multiparametric magnetic resonance images with machine learning-based radiomics models.

This study aimed to evaluate the potential of machine learning-based models for predicting carcinogenic human papillomavirus (HPV) oncogene types using radiomics features from magnetic resonance imaging (MRI). Pre-treatment MRI images of patients with cervical cancer were collected retrospectively. An HPV DNA oncogene analysis was performed based on cervical biopsy specimens. Radiomics features were extracted from contrast-enhanced T1-weighted images (CE-T1) and T2-weighted images (T2WI). A third feature subset was created as a combined group by concatenating the CE-T1 and T2WI subsets. Feature selection was performed using Pearson's correlation coefficient and wrapper- based sequential-feature selection. Two models were built with each feature subset, using support vector machine (SVM) and logistic regression (LR) classifiers. The models were validated using a five-fold cross-validation technique and compared using Wilcoxon's signed rank and Friedman's tests. Forty-one patients were enrolled in the study (26 were positive for carcinogenic HPV oncogenes, and 15 were negative). A total of 851 features were extracted from each imaging sequence. After feature selection, 5, 17, and 20 features remained in the CE-T1, T2WI, and combined groups, respectively. The SVM models showed 83%, 95%, and 95% accuracy scores, and the LR models revealed 83%, 81%, and 92.5% accuracy scores in the CE-T1, T2WI, and combined groups, respectively. The SVM algorithm performed better than the LR algorithm in the T2WI feature subset (P = 0.005), and the feature sets in the T2WI and the combined group performed better than CE-T1 in the SVM model (P = 0.033 and 0.006, respectively). The combined group feature subset performed better than T2WI in the LR model (P = 0.023). Machine learning-based radiomics models based on pre-treatment MRI can detect carcinogenic HPV status with discriminative accuracy.

Electrochemical bioplatform for the determination of the most common and carcinogenic human papillomavirus DNA

Nucleic acid-based analytical bioplatforms have gained importance as diagnostic tests for genomics and as early detection tools for diseases such as cancer. In this context, we report the development of an amperometric bioplatform for the determination of a specific human papillomavirus type 16 (HPV16) sequence. The bioplatform utilizes an immune-nucleic acid hybrid-sandwich assay. A biotinylated RNA capture probe (RNAbCp), complementary to the selected HPV16 target DNA sequence, was immobilised on the surface of streptavidin coated magnetic microbeads (Strep-MBs). The RNA/DNA heteroduplex resulting from the hybridization of the RNAbCP and the HPV16 target sequence was recognised by a commercial antibody that specifically bound to the heteroduplex (AbDNA-RNA). A horseradish-peroxide labeled secondary antibody (antiIgG-HRP) was used for the detection of AbDNA-RNA. Relying on amperometric detection of the resulting HRP-labeled magnetic bioconjugates captured on screen-printed electrodes (SPCEs) in the presence of H2O2 and hydroquinone (HQ), the biotool achieved a low limit of detection (0.5 pM) for the synthetic HPV16 target DNA. In addition, the developed bioplatform was able to discriminate between HPV16 positive and negative human cancer cells using only 25 ng of amplified DNA in a test time of 45 min

Evidence for virus-mediated oncogenesis in bladder cancers arising in solid organ transplant recipients.

A small percentage of bladder cancers in the general population have been found to harbor DNA viruses. In contrast, up to 25% of tumors of solid organ transplant recipients, who are at an increased risk of developing bladder cancer and have an overall poorer outcomes, harbor BK polyomavirus (BKPyV). To better understand the biology of the tumors and the mechanisms of carcinogenesis from potential oncoviruses, we performed whole genome and transcriptome sequencing on bladder cancer specimens from 43 transplant patients. Nearly half of the tumors from this patient population contained viral sequences. The most common were from BKPyV (N=9, 21%), JC polyomavirus (N=7, 16%), carcinogenic human papillomaviruses (N=3, 7%), and torque teno viruses (N=5, 12%). Immunohistochemistry revealed variable Large T antigen expression in BKPyV-positive tumors ranging from 100% positive staining of tumor tissue to less than 1%. In most cases of BKPyV-positive tumors, the viral genome appeared to be clonally integrated into the host chromosome consistent with microhomology-mediated end joining and coincided with focal amplifications of the tumor genome similar to other virus-mediated cancers. Significant changes in host gene expression consistent with the functions of BKPyV Large T antigen were also observed in these tumors. Lastly, we identified four mutation signatures in our cases, with those attributable to APOBEC3 and SBS5 being the most abundant. Mutation signatures associated with an antiviral drug, ganciclovir, and aristolochic acid, a nephrotoxic compound found in some herbal medicines, were also observed. The results suggest multiple pathways to carcinogenesis in solid organ transplant recipients with a large fraction being virus-associated.

Comparative Effects of Bivalent, Quadrivalent, and Nonavalent Human Papillomavirus Vaccines in The Prevention of Genotype-Specific Infection: A Systematic Review and Network Meta-Analysis.

Human papillomavirus (HPV) infection is a major global disease burden and the main cause of cervical cancer. Certain HPV genotypes, with are the most common etiologic pathogens and cause a significant disease burden, are being targeted for vaccine development. However, few studies have focused on the comparative effectiveness of the bivalent HPV (2v-HPV), quadrivalent HPV (4v-HPV), and nonavalent HPV (9v-HPV) vaccines against HPV strain-specific infection. This study investigated the comparative effects of these vaccines against genotype-specific infection. We conducted a pairwise and network meta-analysis of published randomized clinical trials of HPV vaccines according to sex and HPV infection status for nine HPV genotypes (HPV 6/11/16/18/31/33/45/52/58). Overall, 10 randomized controlled trials (12 articles) were included in this study. In the network meta-analysis, no statistically significant differences were observed in the prevention of carcinogenic HPV strains (16/18/31/33/45/52/58) between the 2v-HPV and 4v-HPV vaccines in female HPV infection-naïve populations. However, the 9v-HPV vaccine showed a significantly superior effect compared with 2v-HPV and 4v-HPV vaccines in preventing HPV 31/33/45/52/58 infections. Although 2v-HPV and 4v-HPV vaccines provided some cross-protection against HPV 31/33/45/52/58 infections, the effect was significant only on HPV 31 infection. For HPV 16 and 18, neither statistically significant nor small differences were found in the prevention of HPV infection among the 2v-HPV, 4v-HPV, and 9v-HPV vaccines. Our study complements previous understanding of how the effect of HPV vaccines differs according to the HPV genotype. This is important because HPV genotype prevalence varies among countries. We advocate for continued efforts in vaccinating against HPV, while public health agencies should consider the difference in the vaccine effect and HPV genotype prevalence when implementing HPV vaccination in public vaccination programs.

The significance of high-risk carcinogenic human papillomavirus type identification and vaccination after surgical treatment in the development of cervical intraepithelial neoplasia recurrence

The significance of high-risk carcinogenic human papillomavirus type identification and vaccination after surgical treatment in the development of cervical intraepithelial neoplasia recurrence

Hookworm infection associates with a vaginal Type 1/Type 2 immune signature and increased HPV load.

Helminth infection-driven changes to immunity in the female reproductive tract (FRT) is an immune axis that is currently understudied but can have major implications for the control of FRT infections. Here we address how human hookworm infection associates with vaginal immune profile and risk of Human papillomavirus (HPV) infection. Stool, blood, cervical swabs and vaginal flushes were collected from women from the Central region of Togo to screen for hookworms (Ancylostoma duodenale) and high carcinogenic risk HPV types, via Kato Katz and PCR, respectively. Cytokine, chemokine and immunoglobulin levels were analysed in cervicovaginal lavages and plasma samples. A pronounced mixed Type 1/Type 2 immune response was detected in the vaginal fluids of women with hookworm infection and this immune signature was a notable feature in hookworm-HPV co-infected women. Moreover, hookworm infection is positively associated with increased risk and load of HPV infection. These findings highlight helminth infection as a significant risk factor for acquiring a sexually transmitted viral infection and potentially raising the risk of subsequent pathology.

Differences in integration frequencies and APOBEC3 profiles of five high-risk HPV types adheres to phylogeny

Persistent infection with Human Papillomavirus (HPV) is responsible for almost all cases of cervical cancers, and HPV16 and HPV18 associated with the majority of these. These types differ in the proportion of viral minor nucleotide variants (MNVs) caused by APOBEC3 mutagenesis as well as integration frequencies. Whether these traits extend to other types remains uncertain. This study aimed to investigate and compare genomic variability and chromosomal integration in the two phylogenetically distinct Alpha-7 and Alpha-9 clades of carcinogenic HPV types. The TaME-seq protocol was employed to sequence cervical cell samples positive for HPV31, HPV33 or HPV45 and combine these with data from a previous study on HPV16 and HPV18. APOBEC3 mutation signatures were found in Alpha-9 (HPV16/31/33) but not in Alpha-7 (HPV18/45). HPV45 had significantly more MNVs compared to the other types. Alpha-7 had higher integration frequency compared to Alpha-9. An increase in integration frequency with increased diagnostic severity was found for Alpha-7. The results highlight important differences and broaden our understanding of the molecular mechanisms behind cervical cancer induced by high-risk HPV types from the Alpha-7 and Alpha-9 clades.

Different human papillomavirus types share early natural history transitions in immunocompetent women.

Necessary stages of cervical carcinogenesis include acquisition of a carcinogenic human papillomavirus (HPV) type, persistence associated with the development of precancerous lesions, and invasion. Using prospective data from immunocompetent women in the Guanacaste HPV Natural History Study (NHS), the ASCUS-LSIL Triage Study (ALTS) and the Costa Rica HPV Vaccine Trial (CVT), we compared the early natural history of HPV types to inform transition probabilities for health decision models. We excluded women with evidence of high-grade cervical abnormalities at any point during follow-up and restricted the analysis to incident infections in all women and prevalent infections in young women (aged <30 years). We used survival approaches accounting for interval-censoring to estimate the time to clearance distribution for 20 529 HPV infections (64% were incident and 51% were carcinogenic). Time to clearance was similar across HPV types and risk classes (HPV16, HPV18/45, HPV31/33/35/52/58, HPV 39/51/56/59 and noncarcinogenic HPV types); and by age group (18-29, 30-44 and 45-54 years), among carcinogenic and noncarcinogenic infections. Similar time to clearance across HPV types suggests that relative prevalence can predict relative incidence. We confirmed that there was a uniform linear association between incident and prevalent infections for all HPV types within each study cohort. In the absence of progression to precancer, we observed similar time to clearance for incident infections across HPV types and risk classes. A singular clearance function for incident HPV infections has important implications for the refinement of microsimulation models used to evaluate the cost-effectiveness of novel prevention technologies.