Viral infections associated with oral cancers and diseases in the context of HIV: a workshop report.

Human herpesviruses (HHVs) and human papillomavirus (HPV) are common in the general population and, in immunocompetent people, are mostly carried asymptomatically. However, once an individual becomes immunocompromised by age, illness or HIV infection these dormant viruses can manifest and produce disease. In HIV-positive patients, there is an increased risk of disease caused by HHVs and HPV infections and cancers caused by the oncoviruses Epstein-Barr Virus, HHV-8 and HPV. This workshop examined four questions regarding the viruses associated with oral cancers and disease in the HIV-positive and -negative populations, the immune response, and biomarkers useful for accurate diagnostics of these infections and their sequalae. Each presenter identified a number of key areas where further research is required.

Sustained efficacy and immunogenicity of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine: analysis of a randomised placebo-controlled trial up to 6.4 years.

BACKGROUND: Prophylactic human papillomavirus (HPV) vaccines have to provide sustained protection. We assessed efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine up to 6.4 years. METHODS: Women aged 15-25 years, with normal cervical cytology, who were HPV-16/18 seronegative and oncogenic HPV DNA-negative (14 types) at screening participated in a double-blind, randomised, placebo-controlled initial study (n=1113; 560 vaccine group vs 553 placebo group) and follow-up study (n=776; 393 vs 383). 27 sites in three countries participated in the follow-up study. Cervical samples were tested every 6 months for HPV DNA. Management of abnormal cytologies was prespecified, and HPV-16/18 antibody titres were assessed. The primary objective was to assess long-term vaccine efficacy in the prevention of incident cervical infection with HPV 16 or HPV 18, or both. We report the analyses up to 6.4 years of this follow-up study and combined with the initial study. For the primary endpoint, the efficacy analysis was done in the according-to-protocol (ATP) cohort; the analysis of cervical intraepithelial neoplasia grade 2 and above (CIN2+) was done in the total vaccinated cohort (TVC). The study is registered with ClinicalTrials.gov, number NCT00120848. FINDINGS: For the combined analysis of the initial and follow-up studies, the ATP efficacy cohort included 465 women in the vaccine group and 454 in the placebo group; the TVC included 560 women in the vaccine group and 553 in the placebo group. Vaccine efficacy against incident infection with HPV 16/18 was 95.3% (95% CI 87.4-98.7) and against 12-month persistent infection was 100% (81.8-100). Vaccine efficacy against CIN2+ was 100% (51.3-100) for lesions associated with HPV-16/18 and 71.9% (20.6-91.9) for lesions independent of HPV DNA. Antibody concentrations by ELISA remained 12-fold or more higher than after natural infection (both antigens). Safety outcomes were similar between groups: during the follow-up study, 30 (8%) participants reported a serious adverse event in the vaccine group versus 37 (10%) in the placebo group. None was judged related or possibly related to vaccination, and no deaths occurred. INTERPRETATION: Our findings show excellent long-term efficacy, high and sustained immunogenicity, and favourable safety of the HPV-16/18 AS04-adjuvanted vaccine up to 6.4 years. FUNDING: GlaxoSmithKline Biologicals (Belgium).

HPV vaccination of immunocompromised hosts.

It is well-established that immunocompromised people are at increased risk of HPV-related disease compared with those who are immunocompetent. Prophylactic HPV sub-unit vaccines are safe and immunogenic in immunocompromised people and it is strongly recommended that vaccination occur according to national guidelines. When delivered to immunocompromised populations, HPV vaccines should be given as a 3-dose regimen.

Peripheral blood mononuclear cell markers in antiretroviral therapy-naive HIV-infected and high risk seronegative adolescents. Adolescent Medicine HIV/AIDS Research Network.

OBJECTIVE: To examine potential hematologic and immunologic markers for healthy adolescents and for adolescents infected with HIV. DESIGN: The REACH Project (Reaching for Excellence in Adolescent Care and Health) of the Adolescent Medicine HIV/AIDS Research Network (AMHARN) recruits HIV-infected and high-risk HIV-uninfected adolescents, aged at least 13 but less than 19 years. The study evaluates biomedical and behavioral features of HIV infection as observed while under medical care for HIV infection and adolescent health. METHODS: Blood samples were collected from HIV-infected and HIV-uninfected subjects at 16 clinical sites. Cell phenotypes were determined using standard single, dual or three-color flow cytometry. RESULTS: This report includes data at enrollment for 94 HIV-positive adolescents who had never received antiretroviral therapy (ART) (mean age, 17.4 +/- 1.0 years for males and 16.5 +/- 1.3 years for females) and 149 HIV-negative adolescents (mean age, 16.7 +/- 1.2 years for males and 16.6 +/- 1.2 years for females); this is the antiretroviral therapy-naive subset drawn from 294 HIV-positive and 149 HIV-negative adolescents enrolled in the REACH Cohort. The total leukocyte count was significantly reduced in the HIV-positive females in comparison with the HIV-negative females (P < 0.001). There was a reduction in natural killer cells (P < 0.05) in HIV-positive females (mean, 140.6 +/- 104.2 x 10(6) cells/l) in comparison with HIV-negative females (184.3 +/- 142.5 x 10(6) cells/l), whereas no differences were found between the two groups of males. The reduction in the total CD4 cell count in HIV-positive males and females in comparison with the HIV-negative subjects was the consequence of a decrease in both the naive CD4 and memory CD4 components. There was a striking increase in the mean number of CD8 memory cells in HIV-positive compared with HIV-negative adolescents, and a corresponding increase in the percentage of these cells. In contrast, naive CD8 cells were present in increased numbers but their percentage was decreased. CONCLUSIONS: These studies of adolescents provide normative data for high-risk healthy adolescents as well as baseline immunologic data for a cohort of ART-naive HIV-positive adolescents. This comparison suggests that this untreated, recently infected group had relatively intact immunologic parameters.

Risk factors for abnormal anal cytology in young heterosexual women.

Although anal cancers are up to four times more common in women than men, little is known about the natural history of anal human papillomavirus (HPV) infections and HPV-related anal lesions in women. This study reports on the prevalence of and risks for anal cytological abnormalities over a 1-year period in a cohort of young women participating in a study of the natural history of cervical HPV infection. In addition to their regularly scheduled sexual behavior interviews and cervical testing, consenting women received anal HPV DNA and cytological testing. Anal cytology smears were obtained from 410 women whose mean age was 22.5 +/- 2.5 years at the onset of the study. Sixteen women (3.9%) were found to have abnormal anal cytology: 4 women had low-grade squamous intraepithelial lesions (SILs) or condyloma; and 12 women had atypical cells of undetermined significance. Factors found to be significantly associated with abnormal anal cytology were a history of anal sex [odds ratio (OR), 6.90; 95% confidence interval (CI), 1.7-47.2], a history of cervical SILs (OR, 4.13; 95% CI, 1.3-14.9), and a current anal HPV infection (OR, 12.28; 95% CI, 3.9-43.5). The strong association between anal intercourse and the development of HPV-induced SILs supports the role of sexual transmission of HPV in anal SILs. Young women who had engaged in anal intercourse or had a history of cervical SILs were found to be at highest risk.

Relationship of CD4+ T cell counts and HIV type 1 viral loads in untreated, infected adolescents. Adolescent Medicine HIV/AIDS Research Network.

The REACH Project (Reaching for Excellence in Adolescent Care and Health) of the Adolescent Medicine HIV/AIDS Research Network was designed as a study of an adolescent cohort composed of HIV-1-infected and -uninfected subjects. The goal of the analysis presented was to examine the relationship of CD4+ T cell counts and HIV-1 plasma viral loads in adolescents. The CD4+ T cell counts of 84 HIV+ subjects who were 13 to 19 years of age were measured at the clinical sites, using ACTG standardized techniques. HIV-1 viral loads in frozen plasma were determined by the NASBA/NucliSens assay at a central laboratory. Past and current treatment with antiretroviral drugs was determined by medical record abstraction and interview data. The slope of the line generated by regressing log10 HIV-1 RNA (copies/ml) versus CD4+ T cell counts of REACH subjects who are antiretroviral drug naive was negative and significantly different than zero. A negative association has also been reported for antiretroviral drug-naive, adult males in the Pittsburgh Men's Study, a component of MACS (Pitt-MACS) (Mellors J, et al.: Science 1996;272:1167). These data show that in adolescents, as in adults, HIV-1 RNA concentrations are correlated with corresponding absolute CD4+ T cell count. The slopes of the lines generated with data from each cohort were different (p = 0.003). In addition to age, there are sex and racial differences in the makeup of the two cohorts. Any or all of these differences may affect the slopes of the lines.

Prevalence of and risks for cervical human papillomavirus infection and squamous intraepithelial lesions in adolescent girls: impact of infection with human immunodeficiency virus.

CONTEXT: Data suggest that in adults, human papillomavirus (HPV) infections and their sequalae, squamous intraepithelial lesions (SILs), occur more commonly among human immunodeficiency (HIV)-infected women because of the HIV-associated CD4+ T-cell immunosuppression. Since adolescents are more likely to be early in the course of HIV and HPV infections, the study of both infections in this age group may help elucidate their initial relationship. OBJECTIVE: To examine the prevalence of and risks for cervical HPV infection and SILs by HIV status in a population of adolescent girls. PARTICIPANTS: Subjects recruited at each of the 16 different US sites participating in a national study of HIV infection in adolescents. MAIN OUTCOME MEASURES: Cervical HPV DNA findings using polymerase chain reaction detection techniques and Papanicolaou smear from baseline visits. Infection with HPV was categorized into low- (rarely associated with cancer) and high- (commonly associated with cancers) risk types. RESULTS: Of 133 HIV-infected girls, 103 (77.4%) compared with 30 (54.5%) of 55 noninfected girls were positive for HPV (relative risk [RR], 1.4; 95% confidence interval [CI], 1.1-1.8). The risk was for high-risk (RR, 1.8; 95% CI, 1.2-2.7) but not low-risk (RR, 1.2; 95% Cl, 0.4-3.9) HPV types. Among the girls with HPV infection, 21 (70.0%) of the non-HIV-infected girls had normal cytologic findings compared with only 29 (29.9%) of the HIV-infected girls (P<.001). Multivariate analysis showed that HIV status was a significant risk for HPV infection (odds ratio [OR], 3.3; 95% CI, 1.6-6.7) and SIL (OR, 4.7; 95% CI, 1.8-14.8), but CD4 cell count and viral load were not associated with infection or squamous intraepithelial lesions. Only 9 girls had a CD4+ T-cell count of less than 0.2 cell X 10(9)/L. CONCLUSIONS: High prevalence of HPV infection in both groups underscores the risky sexual behavior in this adolescent cohort. Rates of HPV infection and SILs were higher among HIV-infected girls, despite similar sexual risk behaviors and the relatively healthy state of our HIV-infected group. Infection with HIV may enhance HPV proliferation through mechanisms other than CD4 immunosuppression, particularly early in the course of HIV infection.

Variability of human papillomavirus DNA testing in a longitudinal cohort of young women.

OBJECTIVE: To determine the variability in human papillomavirus (HPV) DNA testing of the cervix in young women found positive for HPV DNA by dot blot hybridization on routine examination. METHODS: Young women who were found to be HPV DNA-positive on routine screening using an RNA-DNA dot blot hybridization method were asked to return for repeat HPV DNA sampling, cytology, colposcopic examination, and biopsy if indicated. Those who had no histologic evidence of cervical dysplasia were asked to return every 4 months for cytology and HPV DNA testing using standardized RNA-DNA hybridization and polymerase chain reaction techniques. RESULTS: The women were followed for a mean of 27.6 months (range 13-40) with a mean of six visits (range four to ten). One-third of the women remained consistently or intermittently HPV DNA-positive by RNA-DNA dot blot hybridization, and almost 50% of the women remained consistently or intermittently positive using polymerase chain reaction techniques. Women were more likely to be positive by polymerase chain reaction than by RNA-DNA hybridization at both 1 year and after 2 years of follow-up (P < .05). However, rates for persistent positive tests by either method were similar at 1 and 2 years of follow-up. Forty percent of the subjects had new or different types than the original HPV type appear during follow-up. All five women who had evidence of spontaneous regression of cytologic abnormalities became HPV DNA-negative by both methods. CONCLUSIONS: Our data suggest that a portion of women infected with HPV appear to eliminate the infection over a relatively short period and are at low or no risk of developing disease. Persistent DNA negativity was also found in those women undergoing spontaneous regression. However, a substantial proportion of women remained intermittently positive by RNA-DNA hybridization and polymerase chain reaction. This finding suggests that the virus remains latent in some individuals and may undergo reactivation, defined by sufficient replication to allow detection by means less sensitive than polymerase chain reaction.

Sexually-transmitted disease in female adolescents: effects of psychosocial factors and high risk behaviors.

BACKGROUND: Although previous studies have reported behavioral correlates of sexually-transmitted diseases (STDs) and psychosocial correlates of risky behavior, research has not examined the linkages between psychosocial attributes, behavioral patterns, and actual STD acquisition within the same adolescent sample. We examined the effects of five psychosocial factors on risky sexual behavior and substance use, and their direct and indirect effects on STD acquisition. METHODS: A multiethnic sample of 571 sexually-active female adolescents (ages 13-19 years) was recruited from family planning clinics. Subjects completed questionnaires prior to their gynecologic examination and STD testing. RESULTS: A multiethnic sample of 571 sexually-active female adolescents (ages 13-19 years) was recruited from family planning clinics. Subjects completed questionnaires prior to their gynecologic examination and STD testing. RESULTS: Female adolescents who were heavy substance users, who felt little control over their sexual behavior, and had a greater number of friends who engaged in risky sexual behavior were themselves more likely to engage in risky sexual behavior. Risky sexual behavior was associated with positive STD status. Subjects who used psychoactive substances during sex reported higher numbers of sexual partners and were more likely to have an STD. CONCLUSIONS: This research has identified possible causal paths by which psychosocial factors may influence specific behaviors that are predictive of STDs in adolescent females.

Female adolescents at high, moderate, and low risk of exposure to HIV: differences in knowledge, beliefs, and behavior.

PURPOSE: To examine differences in the beliefs and behaviors of female adolescents at varying degrees of probable risk for HIV transmission. METHODS: A clinically-based, ethnically diverse sample of 696 sexually active female adolescents was recruited from urban and suburban general adolescent, family planning, and public health clinics. Subjects were categorized into four risk status groups on the basis of their history of IV drug use, sexually transmitted disease (STD), and probable risk of contact with an infected individual (living in a high-risk geographic location, sexual promiscuity, sex with male homo/bisexuals). RESULTS: Females in the highest risk group showed high rates of substance use, anal intercourse, and intentions to have future risky sexual partners. A second high-risk group reported high rates of STDs, inconsistent condom use, and less AIDS knowledge. CONCLUSION: Different subsets of higher risk adolescents may require different intervention strategies.

Sexually transmitted infections among HIV infected and HIV uninfected high-risk youth in the REACH study. Reaching for Excellence in Adolescent Care and Health.

OVERVIEW: This review presents the findings of published research in the Reaching for Excellence in Adolescent Care and Health (REACH) Project on sexually transmitted infections (STIs) within the context of the project's scientific agenda. Methods employed in the study for specimen collection, management, and laboratory analysis are presented. This review presents published analyses of cross-sectional data; longitudinal analyses are underway. In addition, baseline prevalence data on selected STIs and sexual risk profiles of the subjects in REACH are presented. High STI rates were evident in both human immunodeficiency virus (HIV) infected and uninfected youth of both genders regardless of sexual orientation. High infection rates at baseline suggest that prevention-oriented programs for risk reduction among adolescents should focus on both HIV infected and at-risk, uninfected youth.

HIV-related oral manifestations among adolescents in a multicenter cohort study.

PURPOSE: To describe baseline prevalence of oral mucosal diseases among HIV infected adolescents in relationship to biological and behavioral risk factors. METHODS: Participants in Reaching for Excellence in Adolescent Care and Health (REACH), a multicenter longitudinal observational study of HIV/AIDS in adolescents, received physical examinations, blood tests, and oral examinations at 3-month intervals. We evaluated participants for oral conditions commonly seen in relationship to HIV, and explored the association of the most common lesion with selected biological and behavioral variables at baseline using contingency tables and Fisher's Exact test. RESULTS: Among 294 HIV infected adolescents recruited between March 1996 and March 1999, the majority were female (75%), aged 17 to 18 years (69%), and African-American (73%). More than 90% had a CD4(+) T-lymphocyte count > 200 cells/mm(3) at baseline and 57% had a plasma HIV-1 RNA concentration

Psychological distress among HIV(+) adolescents in the REACH study: effects of life stress, social support, and coping. The Adolescent Medicine HIV/AIDS Research Network.

PURPOSE: To investigate the effects of life events, social support, and coping on anxiety and depression among human immunodeficiency virus (HIV)-infected adolescents. It was hypothesized that higher levels of stressful events would be associated with higher levels of anxiety and depression, but that this association would be moderated by satisfaction with social support and by adaptive coping. METHODS: HIV-infected adolescents from 16 locations in 13 U.S. cities (N = 230, median age 16.09 years, standard deviation 1.2, range 13-19; 77% females) were recruited into the Reaching for Excellence in Adolescent Care and Health (REACH) project. REACH is the first large-scale disease progression study of HIV(+) adolescents infected through sexual behavior or injection drug use. The adolescent assessment was conducted by audio-computer assisted self-interview. Least squares regressions were used to test hypotheses. RESULTS: Life events with high impact were associated with higher levels of depression and anxiety. Frequently reported events included: being prescribed medications (74%), family financial problems (61%), and parental alcohol abuse (20%). Contrary to expectations, the buffering hypotheses of social support and adaptive coping were not supported. Satisfaction with social support and adaptive coping methods were both associated directly with lower levels of depression, but no association was detected between these two measures and anxiety. CONCLUSIONS: Although life event distress was directly associated with psychological distress, neither social support nor adaptive coping seemed to moderate this association. However, both satisfaction with support and adaptive coping were associated directly with depression in HIV-infected adolescents.

Comparison between colposcopic, cytologic, and histologic findings in women positive and negative for human papillomavirus DNA.

Little is known about the role of detection of human papillomavirus (HPV) DNA in exfoliated cells of the cervix in aiding the colposcopic diagnosis of cervical lesions. The purpose of our study was to compare the colposcopic findings of young women who were positive and negative for HPV DNA. Eighty-four women aged 13-22 years attending family planning clinics were examined colposcopically with the aide of acetic acid and Lugol's solution and without knowledge of HPV DNA status. Lesions identified were given scores based on the severity of observed colposcopic changes. Samples for cytology and HPV DNA testing, which included types 6, 11, 16, 18, 31, 33, and 35, were obtained at the time of the examination. Biopsies were performed on women with significant lesions identified on examination or with cytology suggestive of neoplasia. Students t-test and chi 2 analysis were performed to compare colposcopic variables and HPV DNA type. Of the 84 women examined, 17 were positive for HPV DNA; 9 had type 16/18. The average length of sexual activity was 2.7 years. Women with HPV 16/18 had a mean of 1.7 lesions visible at colposcopy compared to 0.7 lesions visible in those negative for HPV 16/18 (this included HPV DNA negative women and women positive for HPV types 6, 11, 31, 33, and 35) (p < 0.001). Women who were positive for HPV 16/18 also had higher lesional scores than the HPV 16/18-negative group (3.4 versus 1.0, respectively, p < 0.001). All four women who had dysplasia either on cytology or histology were positive for type 16/18.(ABSTRACT TRUNCATED AT 250 WORDS)

No change in health risk behaviors over time among HIV infected adolescents in care: role of psychological distress.

PURPOSE: To investigate the association of psychological distress and health risk behaviors among HIV infected adolescents. It was hypothesized that higher levels of distress would be associated with increased sexual risk behaviors, and increased use of alcohol and drugs. METHODS: HIV infected adolescents (N = 323) were recruited into an observational study in 15 clinical sites; for the 323 subjects, a total of 1212 visits were used in a repeated measures analysis. Data on depression (using the CES-D), anxiety (manifest anxiety scale), sexual behaviors and alcohol and marijuana use were obtained through computer-assisted self-administered interview. RESULTS: Approximately 65% of the sample was sexually active across all six study visits, with approximately 43% consistently reporting having unprotected sex at last intercourse. Higher levels of depression were associated with frequent alcohol use and with unprotected sex at last intercourse, with depressed adolescents significantly more likely to have had unprotected sex than those who were not depressed. Health anxiety was associated with frequent marijuana use and with recent sexual activity, and physiological anxiety was also associated with recent sexual activity. CONCLUSIONS: Despite the fact that these HIV infected adolescents are all engaged in primary care, overall the sample is maintaining its high-risk sexual behavior. In addition, these adolescents may be self-medicating to deal with health-related anxiety. Health interventions for HIV infected adolescents should examine whether psychological distress is contributing to maintenance health risk behaviors.

The REACH Project of the Adolescent Medicine HIV/AIDS Research Network: design, methods, and selected characteristics of participants.

PURPOSE: To describe the Reaching for Excellence in Adolescent Care and Health (REACH) Project of the Adolescent Medicine Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) Research Network, a unique collaborative effort to conceive and implement a research design intended to examine HIV pathogenesis, pubertal hormonal variation, and the effects of sexually transmitted disease comorbidity in HIV-infected youth to improve their health care. METHODS: This multidisciplinary team has drawn on basic science and clinical experience to produce a study design with relevant and feasible study aims and testable hypotheses. Particular attention has been paid to centralized training and quality control practices. Standardized measurements include direct and computer interviews, physical examination, laboratory analysis, and medical chart abstraction. The protocol has been approved by local institutional review boards. RESULTS: A highly standardized and quality control monitored protocol has been implemented at 16 sites throughout the United States collecting historical, observational, and laboratory data in a group of HIV-infected adolescents and HIV-negative controls. Preliminary data collected on subjects are consistent with published reports of the sociodemographic and clinical characteristics of the HIV epidemic in sexually active youth, thus supporting the integrity of the protocol development process. The study population is, for the most part, in older adolescence, predominantly minority and female, and with publicly financed or no health insurance. CONCLUSIONS: The REACH Project is positioned to address questions about the clinical course, immunologic profile, and viral dynamics in HIV-positive youth, and thus is able to inform drug development and management strategies for this understudied population.

Human papillomavirus infection in adolescents.

The recent gain in knowledge of the genomic function of HPV has led to a greater understanding of the natural history of HPV infection in women, starting from infection to the development of invasive cancer. LSIL is reflective of a benign process associated with HPV replication, and in the majority of women, HPV is eradicated or put into some type of immunologic control so that it remains undetected. In contrast, in the minority of women who have persistent infection, HSIL and invasive cancer are more likely to occur. These findings can be translated clinically to suggest that LSIL can be followed up for a defined period of time and that HPV testing in older women may be useful to identify persistent HPV infections and subsequent risk for invasive cancers.

The pediatrician and the sexually active adolescent. A primer for sexually transmitted diseases.

Sexual activity is a common practice among young adolescents, placing them at high risk for STDs, many of which have long-term consequences. Early diagnosis and treatment are essential to limit both the consequences and the spread of these infections. The clinician has a responsibility to the adolescent patient to recognize and treat these diseases. Using history and physical examination, the clinician should be able to determine an adolescent's risk for an STD, and, based on this risk, undertake the appropriate evaluations. Patient treatment, follow-up, and management of sex partners are then guided by the results of either presumptive or definitive diagnostic tests.

Genital HPV infections in children and adolescents.

Major differences in estrogen and progesterone levels and in vaginal/cervical cell types exist among children, adolescents, and adults, which may help explain the observed differences in the prevalence of HPV among these groups. Although sexual transmission occurs in both children and adolescents, the persistence of genital HPV in the neonate from maternal transmission is highly questionable. The discordances in HPV types between neonatal transmission studies and the studies in older children have yet to be explained. Neonatal infections seem to be predominantly types 16 and 18 and persist for short periods in the genital area. The majority of condylomatous lesions in children are HPV types 6 and 11. Acquisition of HPV during childhood and adolescence is not an immediate cause of severe morbidity. However, significant evidence suggests that early exposure not only hastens the development of anogenital cancers but may also increase the actual risk of cancer. Future studies should include large-scale longitudinal designs to test and follow neonates with careful attention to sexual abuse issues during the prospective period so that we may confidently diagnose and appropriately treat children with HPV infections. The role of age and immunity remains confusing, supporting the need for studies to examine cervical immunity more closely.

Human papillomavirus infections in women with HIV disease: prevalence, risk, and management.

Among the most common coinfections and comorbidities associated with the immunosuppression induced by HIV are human papillomavirus (HPV) and its associated diseases: external genital warts, low- and high-grade squamous intraepithelial lesions, and genital squamous cell cancers. Studies have consistently shown that HPV infections in HIV-seropositive women are detected more frequently, are more persistent, and are more difficult to treat than are those in HIV-seronegative women. This article reviews the prevalence, risk, and management of HPV associated infections in HIV-seropositive women.