Rationale and design of the Anal HPV, HIV and Aging (AHHA) study: Protocol for a prospective study of anal HPV infection and HSIL among men who have sex (MSM) or trans women living with and without HIV, ages 50 and older.

Introduction: More than half of people living with HIV in the US are 50+ years old. Despite the benefits of antiretroviral therapy, older individuals with HIV are at higher risk for illnesses than their HIV-negative counterparts. Anal cancer, anal high-grade squamous intraepithelial lesions (HSIL), and anal HPV-16 infection occur most frequently among men who have sex with men living with HIV (MSMLWH). Men aged 60+ are 3-fold more likely to be diagnosed with anal cancer compared with younger men. Despite the increasing risk of anal cancer with age and HIV, little is known about the relationships among aging, HPV infection, HSIL and HIV. Methods and analysis: The Anal HPV, HIV, and Aging (AHHA) Study is a two-stage project to evaluate the relationships among anal HPV infection, HSIL, HIV infection, and biomarkers of biological aging in MSM or trans women over the age of 50 years. Stage 1 will estimate the cross-sectional prevalence of both anal HPV infection and HSIL, based on outcomes of anal HPV DNA testing, and high-resolution anoscopy with biopsy. We will also study associations with study outcomes and serological biomarkers of inflammation (interleukin-6, C-reactive protein, D-dimer) and with the Veterans Aging Cohort Study Index and the Fried Frailty Phenotype using multivariable models. Participants living with HIV (n = 150) and HIV-negative participants (n = 150) will be enrolled. The 3-year Stage 2 longitudinal sample restricted to HSIL-negative and anal HPV-16 DNA-negative participants will estimate the 3-year incidence of both anal HSIL and anal HPV, stratified by HIV status through Cox proportional hazards regression. The effect of biomarkers of inflammation and markers of aging on study outcomes will be evaluated through multivariable repeated measures models stratified by HIV status. Ethics and dissemination: This protocol was approved by the University of California, San Francisco Institutional Review Board (IRB: 16-18966). Results will be disseminated through presentations at national/international scientific conferences and publication in peer-reviewed journals.

Developing Human Skin Contains Lymphocytes Demonstrating a Memory Signature.

Lymphocytes in barrier tissues play critical roles in host defense and homeostasis. These cells take up residence in tissues during defined developmental windows, when they may demonstrate distinct phenotypes and functions. Here, we utilized mass and flow cytometry to elucidate early features of human skin immunity. Although most conventional αß T (Tconv) cells in fetal skin have a naive, proliferative phenotype, a subset of CD4+ Tconv and CD8+ cells demonstrate memory-like features and a propensity for interferon (IFN)γ production. Skin regulatory T cells dynamically accumulate over the second trimester in temporal and regional association with hair follicle development. These fetal skin regulatory T cells (Tregs) demonstrate an effector memory phenotype while differing from their adult counterparts in expression of key effector molecules. Thus, we identify features of prenatal skin lymphocytes that may have key implications for understanding antigen and allergen encounters in utero and in infancy.

MAIT cells are imprinted by the microbiota in early life and promote tissue repair.

How early-life colonization and subsequent exposure to the microbiota affect long-term tissue immunity remains poorly understood. Here, we show that the development of mucosal-associated invariant T (MAIT) cells relies on a specific temporal window, after which MAIT cell development is permanently impaired. This imprinting depends on early-life exposure to defined microbes that synthesize riboflavin-derived antigens. In adults, cutaneous MAIT cells are a dominant population of interleukin-17A (IL-17A)-producing lymphocytes, which display a distinct transcriptional signature and can subsequently respond to skin commensals in an IL-1-, IL-18-, and antigen-dependent manner. Consequently, local activation of cutaneous MAIT cells promotes wound healing. Together, our work uncovers a privileged interaction between defined members of the microbiota and MAIT cells, which sequentially controls both tissue-imprinting and subsequent responses to injury.

Biomarkers of oral inflammation in perinatally HIV-infected and perinatally HIV-exposed, uninfected youth.

AIM: To examine oral biomarkers that have been associated with periodontal disease progression in HIV-infected adults in perinatally HIV-infected and HIV-exposed but uninfected youth. MATERIAL AND METHODS: This was a cross-sectional, multicentre substudy of youth participating in the Oral Health Pediatric HIV/AIDS Cohort study. Gingival crevicular fluid repository samples from participants with and without periodontal disease (using Gingival Index [GI] and Bleeding on Probing [BOP] parameters on dental examination) were tested for concentration levels of inflammatory biomarkers. Associations were assessed using Wilcoxon test and Spearman correlation. RESULTS: For perinatal HIV youth (n = 129), the markers consistently elevated (p < .05) in sites with GI ≥2 and in sites with BOP were interleukin-1ß, 6 and 13, macrophage inflammatory protein-1α and metalloproteinase-9. Serum tumour necrosis factor-α and soluble CD14 were positively correlated with a summary count of elevated cytokines. No associations were seen among HIV-uninfected subjects (n = 71). CONCLUSIONS: The association of oral biomarkers of inflammation with clinical indicators of periodontal inflammation and systemic immune activation suggests that perinatal HIV-infected youth may be at higher risk for developing significant periodontal disease, associated with tooth loss and HIV progression. More frequent dental care of this group is needed to prevent potential periodontal progression.

Adventitial Stromal Cells Define Group 2 Innate Lymphoid Cell Tissue Niches.

Type 2 lymphocytes promote both physiologic tissue remodeling and allergic pathology, yet their physical tissue niches are poorly described. Here, we used quantitative imaging to define the tissue niches of group 2 innate lymphoid cells (ILC2s), which are critical instigators of type 2 immunity. We identified a dominant adventitial niche around lung bronchi and larger vessels in multiple tissues, where ILC2s localized with subsets of dendritic and regulatory T cells. However, ILC2s were most intimately associated with adventitial stromal cells (ASCs), a mesenchymal fibroblast-like subset that expresses interleukin-33 (IL-33) and thymic stromal lymphopoietin (TSLP). In vitro, ASCs produced TSLP that supported ILC2 accumulation and activation. ILC2s and IL-13 drove reciprocal ASC expansion and IL-33 expression. During helminth infection, ASC depletion impaired lung ILC2 and Th2 cell accumulation and function, which are in part dependent on ASC-derived IL-33. These data indicate that adventitial niches are conserved sites where ASCs regulate type 2 lymphocyte expansion and function.

Toll-like receptors: Important immune checkpoints in the regression of cervical intra-epithelial neoplasia 2.

Toll-like receptors (TLRs) are innate immune defenders thought to be critical for the clearance of human papillomavirus (HPV) infections hence preventing the development of HPV-associated high-grade cervical intra-epithelial neoplasia (CIN2 or 3), a potential cervical cancer precursor. However, the role of TLRs in the regression of established cervical lesions, such as CIN2, is hindered by a lack of prospective design studies. Using SYBR green real-time PCR assays, we have examined the gene expression of TLR2, TLR3, TLR7, TLR8 and TLR9, in cytobrush collected endocervical cells of 63 women diagnosed with CIN2 at study entry (baseline) and followed over a 3-year period. Wilcoxon rank-sum test was used to examine the association between TLR expression levels, measured at baseline, and CIN2 outcome (regression vs. persistence/progression) over time. HPV genotyping was performed using Roche Linear Array Assay detecting 37 HPV types. Women with CIN2 regression showed significantly higher baseline levels of TLR2 (p = 0.006) and TLR7 (p = 0.007), as well as a non-significant trend for a higher TLR8 expression (p = 0.053) compared to women with CIN2 persistence/progression. Six women with CIN2 regression, who presented with an HR-HPV DNA-negative CIN2 lesion at study entry, had significantly higher baseline levels of TLR2 (p = 0.005), TLR7 (p = 0.013) and TLR8 (p = 0.012), compared to women with CIN2 persistence/progression, suggesting their role in clearance of HPV prior to clearance of the lesion. Our results confirm a key role of TLRs in regression of CIN2 and support the potential use of TLR-agonists for treatment of these lesions.

Prevalence and Transmission of Beta and Gamma Human Papillomavirus in Heterosexual Couples.

BACKGROUND: Beta (ß) and gamma (γ) human papillomavirus (HPV) are commonly found on the skin. Few of the ß types are associated with nonmelanoma skin cancer. Little is known about transmission patterns of these HPV, specifically in the anogenital (AG) areas. The primary objective of this study was to examine the AG concordance and transmission of ß and γHPV types between heterosexual couples. METHODS: Archival samples from a previously published study examining concordance of alpha HPV types between couples were tested for ß and γHPV. Hand, mouth, and genital samples were obtained 5 times over a 6-week period. RESULTS: Of the 21 couples examined, ß and γHPV were detected in AG sites in 67% and 30% of men, respectively, and 41% and 25% of women. Positive concordance for ß and γHPV was 27% and 20%, respectively, which was greater than the observed concordance between noncouples (10% for ßHPV and 4% for γHPV). Transmission rate of ßHPV between AG areas was 15.9 (95% confidence interval [CI], 3.3-46.5) per 100 person months for men-to-women at risk and for γHPV was 6.6 (95% CI, .2-36.7). Risks for women-to-men were similar. CONCLUSIONS: Beta and γHPV are common in the AG area, and data suggest that they can be sexually transmitted.

Oral Human Papillomavirus in Youth From the Pediatric HIV/AIDS Cohort Study.

In contrast to high rates of oral human papillomavirus (HPV) found in human immunodeficiency virus (HIV)-infected adults, only 2% of 209 perinatally HIV-infected youth had oral HPV. This rate was similar in HIV-exposed but uninfected youth. No association was found with sexual activity; however, low CD4 counts were associated with oral HPV.

Development of a novel liquid bead array human papillomavirus genotyping assay (PGMY-LX) and comparison with linear array for continuity in longitudinal cohort studies.

Studies of the natural history of human papillomavirus (HPV) infection require reproducible, type-specific testing of the viral types that infect cervical tissue; Linear Array (LA) is one method that has been widely used. We sought to develop a cost-effective, high-throughput alternative using the same PGMY09/11 primer/probe system and offering sensitivity and specificity comparable to those with LA to ensure continuity in longitudinal studies. We report here on a Luminex-based approach, PGMY-LX, that offers type-specific detection of 33 oncogenic and nononcogenic types. Detection of HPV type-specific plasmid DNA was highly specific, with high signal-to-noise ratios for all types except nononcogenic type 40 and no cross-reactivity between types. Cohen's unweighted κ values for 378 clinical samples tested by both LA and PGMY-LX were ≥0.8 (range, 0.80 to 1.0) for 25 types, including oncogenic HPV types 16, 31, 33, 39, 45, 58, and 59 and possibly oncogenic types 53, 66, 73, and 82) and >0.7 (range, 0.74 to 0.79) for oncogenic types 18, 35, 51, and 56 and probable oncogenic type 68b, indicating substantial or better type-specific agreement between the two methods. The reproducibility by PGMY-LX of the types detected by LA varied from 94% when a single HPV type was present to 66% when multiple types were present. The interrun reproducibility for PGMY-LX varied from 98% for single-type infections to 85% for multiple-type infections. The high reproducibility of PGMY-LX and the type-specific agreement with LA allows PGMY-LX to be incorporated into longitudinal, cohort studies that have historically relied on LA.

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.

Human papillomavirus infections in nonsexually active perinatally HIV infected children.

Although human papillomavirus (HPV) infections are common in HIV-infected adults, little is known about children. Our objective was to examine the prevalence of and risks for HPV of the oral mucosal and external genital areas in nonsexually active (NSA) perinatally (P) HIV+ children and compare with HIV-exposed but uninfected (HEU) children. A convenience sample attending a pediatric clinic were enrolled. Samples for HPV were obtained from the oral and anogenital areas and tested for one of 37 HPV types. The mean age of the 48 PHIV+ children was 14.3±3.9 years vs. 6.2±4.8 for the 52 HEU (p<0.001). Of the 23 PHIV+ girls, 30.4% had anogenital and 17% had oral HPV, and of the 27 HEU girls, 2 (7.4%) anogenital and 0 had oral HPV. Of the boys, 4/23 (17.4%) and 1/25 (4%) PHIV+ had anogenital and oral HPV, respectively, and 3/24 (12.5%) and 1/25 (4%) HEU had anogenital and oral HPV, respectively. Rates of HPV did not differ by age among the PHIV+, whereas older HEU were more likely to have HPV than younger HEU (p=0.07). This large age gap precluded statistical comparison by HIV status. The presence of HPV in NSA PHIV+ children may have implications regarding HPV vaccination efficacy.

Natural history of anal human papillomavirus infection in heterosexual women and risks associated with persistence.

BACKGROUND: Anal cancer is more common in women than in men, yet little is known about the natural history of human papillomavirus (HPV) in women. The objective was to examine the natural history of anal HPV in heterosexual women. METHODS: Young women participating in an HPV cohort study were seen at 4-month intervals for cervical and anal HPV testing. Time to clearance was estimated using the Kaplan-Meier approach; risks for persistence were assessed using Cox regression models. RESULTS: Seventy-five women (mean age, 23.5 ± 4.1 years) who tested positive for anal HPV were followed for a mean of 84.5 ± 44.9 months. By 3 years, 82.5% of anal non-16 high-risk (HR) HPV, 82.6% of low-risk (LR) HPV, and 76.2% of HPV-16 infections had cleared. By 3 years, only 36.4% of women had become negative for all HPV types. In the multivariable model, concurrent cervical HPV-16 (P < .001), weekly alcohol use (P = .015), anal touching during sex (P = .045), recent anal sex (P = .04), and no condom use during anal sex (P = .04) were associated with HPV-16 persistence. Greater number of new sex partners (P = .024) and condom use during vaginal sex (P = .003) were associated with clearance. Similar associations were found for clearance in all HR-HPV infections. Only concomitant cervical HPV was associated with non-16 HR-HPV persistence. CONCLUSIONS: The majority of anal HPV infections cleared within 3 years. HPV-16 infections were slower to clear than other HR-HPV infections, consistent with its role in anal cancer. Specific sexual behaviors were associated with persistence, suggesting that education and behavioral interventions may decrease persistence.

Redetection of cervical human papillomavirus type 16 (HPV16) in women with a history of HPV16.

BACKGROUND: The purpose of this study was to examine the rate of and risks for cervical human papillomavirus type 16 (HPV16) redetection in women with documented or suspected HPV16 infection. METHODS: A convenience sample of women aged 13-21 years were seen at 4-month intervals for HPV DNA testing and cytology. Serum samples were obtained at baseline and annually. RESULTS: A total of 1543 women entered the study. Of the 295 women with detection of HPV16 DNA and subsequent clearance, 18.1% had HPV16 redetected by 8.5 years (88% cleared this second detection by 3 years). Of the 247 women who had antibodies to HPV16 and were HPV16 DNA negative at baseline, 15.3% had HPV16 redetected by year 5. Risks for redetection included douching, current use of medroxyprogesterone, reporting >1 sex partner or having a new sex partner, and having a sexually transmitted infection. Development of cervical intraepithelial neoplasia 2/3 was rare in women with redetection, except for those with prevalent HPV16 infection. CONCLUSIONS: Reappearance of HPV16 DNA was observed in 18% of women. Most are associated with sexual exposure and appear benign. Interpretation of the studies is more complex in women with prevalent infections as it appears that this small subset reflects women with persistence already present at entry.

Concordance and transmission of human papillomavirus within heterosexual couples observed over short intervals.

BACKGROUND: Because many human papillomavirus (HPV) infections are transient, rates of transmission may be miscalculated if the interval between testing spans several months. We examined rates of concordance and transmission in heterosexual couples over short intervals. METHODS: Twenty-five adult couples were enrolled and sampled for HPV DNA from the genitals, hand, and mouth 5 times over a 6-week period, including 24 hours after sexual intercourse and after 48 hours of abstinence. Concordance and transmission patterns were described. RESULTS: Concordance between the couple's genital sites ranged from 64% to 95% for at least 1 HPV type. The highest rates of concordance were observed 24 hours after sexual intercourse. A similar peak in concordance was not seen between genital and nongenital anatomic sites. Transmission rates for female genital to male genital ranged from 26.8 to 187.5 per 100 person-months and for male genital to female genital from 14.5 to 100 per 100 person-months. CONCLUSIONS: High rates of concordance shortly after intercourse suggest that some DNA detections in the genital area are contaminants from a partner and not established HPV infections. Female-to-male transmission appeared more common than male-to-female transmission.

Active squamous metaplasia of the cervical epithelium is associated with subsequent acquisition of human papillomavirus 16 infection among healthy young women.

BACKGROUND: Vulnerability of younger women to human papillomavirus 16 (HPV16) infection has been attributed to the predominance of ectocervical columnar epithelia in this age group. However, squamous metaplastic tissue may be more influential. We examined the extent of ectopy and metaplastic activity as risks for HPV16 acquisition in a prospective cohort. METHODS: Participants were HPV16 negative at the first two visits. Follow-up occurred every 4 months. Ectopy was quantitatively measured on colpophotographs. We calculated metaplastic rate as the difference in ectopy between visits. Cox proportional hazards models were constructed, adjusting for several covariates. RESULTS: Analyses included 198 women (mean baseline age 17 years) for 1734 visits. Mean follow-up was 4.4 years. Incident HPV16 was detected in 36 (18%) women. Metaplastic rate between the two visits before HPV16 detection was significantly associated with incident infection (hazard ratio [HR], 1.17; confidence interval [CI], 1.02-1.33; P = .02). However, ectopy was not significant, whether measured before or concurrent to HPV16 detection (HR range, 0.99-1.00; CI range, .97-1.02; P range, .47-.65). CONCLUSIONS: Dynamic metaplasia rather than the sheer extent of ectopy appears to increase risk for incident HPV16 in healthy young women. This in vivo observation is consistent with the HPV life cycle, during which host cell replication and differentiation supports viral replication.

Cervical ectopy and the acquisition of human papillomavirus in adolescents and young women.

OBJECTIVE: Higher rates of human papillomavirus (HPV) in adolescents and younger women have been attributed to their greater extent of "cervical ectopy," defined as columnar and metaplastic epithelia on the ectocervix. Our objective was to estimate associations between ectopy and incident HPV in healthy adolescents and young women. METHODS: Enrolled between October 2000 and October 2002, this prospective cohort included women aged 13-21 years who were sexually active, without previous cervical intraepithelial neoplasia, cervical procedures, or immunosuppression, with menarche within 6 years before enrollment, and negative for HPV DNA at baseline. Every 4 months, extent of ectopy was quantitatively measured using colpophotography and computerized planimetry. Cox proportional hazards models examined associations between ectopy and incident HPV, defined as the first positive HPV result during follow-up. RESULTS: The 138 women attended 509 total visits. At baseline, mean age was 16.7 years and mean extent of ectopy was 25% of the total cervical face. Incident HPV of any type was detected in 42 (30%) women and was not significantly associated with baseline ectopy (hazard ratio 1.09, 95% confidence interval 0.96-1.25; P=.20; ectopy in units of 10%), or with ectopy measured 4 months before HPV detection (hazard ratio 1.09, confidence interval 0.94-1.26; P=.25). Our sample size had 80% power to detect a hazard ratio of 1.9 (with two-tailed α=0.05). Results were similarly insignificant for HPV subgroupings of incident high-risk, low-risk, α9, and α3/α15 types, and when adjusted for new sexual partners. CONCLUSION: Extent of cervical ectopy was not associated with HPV acquisition in healthy adolescents and young women. Biological vulnerabilities may lie in immune function or other characteristics of the cervical epithelium. LEVEL OF EVIDENCE: II.

CD8 T-cell responses in incident and prevalent human papillomavirus types 16 and 18 infections.

CD8 T-cell responses were examined in subjects with incident (new following negative visits) or prevalent (lasting ≥ 4 months) human papillomavirus type 16 (HPV16) or human papillomavirus (HPV18) infection. The groups were chosen from a cohort of women being followed every 4 months with cervical cytology and HPV-DNA testing. Enzyme-linked immunospot (ELISPOT) assay was performed at enrollment (time zero) and one year later. At time zero, 1 (6%) of 17 subjects with incident HPV 16/18 infections had positive ELISPOT results which increased to 6 (35%) at one year. For the subjects with prevalent HPV 16/18 infections, the ELISPOT results were similar at time zero (2 (15%) of 15 subjects positive) and at one year (3 (20%)). While all of the 11 women with prevalent HPV16 infection showed clearance one year later, unexpectedly only 1 (25%) of 4 women with prevalent HPV18 infection demonstrated clearance one year later (P = .009).

Association between toll-like receptor expression and human papillomavirus type 16 persistence.

The mechanisms involved in mucosal immune control of cervical human papillomavirus (HPV) infection remain ill defined. Because toll-like receptors (TLRs) are key players in innate immune responses, we investigated the association between TLR expression and viral persistence or clearance in young women with incident infections with oncogenic HPV types 16 or 51. Messenger RNA expression of TLR1, TLR2, TLR3, TLR4, TLR6, TLR7, TLR8 and TLR9 was measured by quantitative reverse transcription-PCR using human endocervical specimens, collected before and after viral acquisition, in a cohort well characterized for HPV infections. Wilcoxon rank sum test was used to compare the change seen from preinfection to incident infection between women who subsequently cleared infection with those who did not. HPV 16 infections that cleared were significantly (p < 0.05) associated with an increase in expression of the four viral nucleic acid-sensing TLRs (TLR3, TLR7, TLR8 and TLR9) as well as TLR2 upon viral acquisition. Similar associations were not observed for HPV 51. In women who subsequently cleared their HPV 16 infection, changes in TLR1, TLR3, TLR7 and TLR8 expression levels between preincident and incident visits were significantly correlated with parallel changes in the levels of interferon-α2, measured by immunoassay in cervical lavage specimens. This study suggests that dampened TLR expression in the cervical mucosa is a type-specific mechanism by which HPV 16 interferes with innate immune responses, contributing to viral persistence, and that TLR upregulation and resultant cytokine induction is important in subsequent viral clearance.

Rate of and risks for regression of cervical intraepithelial neoplasia 2 in adolescents and young women.

OBJECTIVE: To describe the natural history of cervical intraepithelial neoplasia (CIN) 2 in a prospective study of adolescents and young women, and to examine the behavioral and biologic factors associated with regression and progression. METHODS: Adolescents and women aged 13 to 24 years who were referred for abnormal cytology and were found to have CIN 2 on histology were evaluated at 4-month intervals. Risks for regression were defined as three consecutive negative cytology and histology visits, and progression to CIN 3 was estimated using Cox proportional hazards regression models. RESULTS: Ninety-five patients with a mean age of 20.4 years (±2.3) were entered into the analysis. Thirty-eight percent resolved by year 1, 63% resolved by year 2, and 68% resolved by year 3. Multivariable analysis found that recent Neisseria gonorrhoeae infection (hazard ratio 25.27; 95% confidence interval [CI] 3.11-205.42) and medroxyprogesterone acetate use (per month) (hazard ratio 1.02; 95% CI 1.003-1.04) were associated with regression. Factors associated with nonregression included combined hormonal contraception use (per month) (hazard ratio 0.85; 95% CI 0.75-0.97) and persistence of human papillomavirus (HPV) of any type (hazard ratio 0.40; 95% CI 0.22-0.72). Fifteen percent of patients showed progression by year 3. HPV 16/18 persistence (hazard ratio 25.27; 95% CI 2.65-241.2; P=.005) and HPV 16/18 status at last visit (hazard ratio 7.25; 95% CI 1.07-49.36; P<.05) were associated with progression Because of the small sample size, other covariates were not examined. CONCLUSION: The high regression rate of CIN 2 supports clinical observation of this lesion in adolescents and young women.

The role of sexual behavior and human papillomavirus persistence in predicting repeated infections with new human papillomavirus types.

BACKGROUND: Although human papillomavirus (HPV) infections are common in young women, the rate of and risk for repeated new infections are not well documented. We examined the rate of and risks for new HPV detection in young women. METHODS: We used data from an ongoing study of HPV, initiated in 1990. Sexually active women ages 12 to 22 years were eligible. Interviews on behaviors and HPV testing were done at 4-month intervals; sexually transmitted infection (STI) testing was annual or if symptomatic. Starting with first HPV detection, time to the next (second) visit (event) with detection of new HPV types, and then the second event to time to third event was calculated. Risks were determined using Cox proportional hazard model. RESULTS: Sixty-nine percent of 1,125 women had a second event, and of those with a second event, 63% had a third event by 3 years, respectively. Women with HPV persistence from initial visit to second event [hazard ratio (HR) = 4.51 (3.78-5.37)], an STI [HR = 1.47 (1.00-2.17)], bacterial vaginosis [HR = 1.60 (1.07-2.39)], and number of new sex partners [HR = 1.10 (1.05-1.15 per partner/mo)] were independent associations for HPV. Risks for third event were similar. CONCLUSION: This study documents the repeated nature of HPV infections in young women and their association with sexual risk behaviors. IMPACT: This finding underscores the lack of clinical utility of HPV testing in young women. Further studies are needed to examine host factors that lead to HPV acquisition and persistence.