Monitoring HPV type-specific prevalence over time through clinic-based surveillance: a perspective on vaccine effectiveness.

We investigated the feasibility of monitoring trends in prevalence of vaccine-preventable human papillomavirus (HPV) types in different clinic populations. We collected cervical specimens from women presenting to family planning, primary care, and sexually transmitted disease (STD) clinics for routine pap smears in five US cities during 2003-2005. We performed HPV genotyping and calculated annual type-specific prevalences; pre-vaccine era prevalence was highest for HPV 16 (6.0; 95% confidence interval [CI] 5.5-6.6%) and annual prevalences for vaccine-preventable types were stable, with few exceptions, after controlling for clinic type, age group, and city. With sufficient sample size and stable population characteristics, clinic-based surveillance systems can contribute to monitoring HPV vaccine impact in the cervical screening population.

Epidemiology of human papillomavirus infection among fishermen along Lake Victoria Shore in the Kisumu District, Kenya.

OBJECTIVES: The epidemiology of human papillomavirus (HPV) infection in men in Kenya is largely uncharacterized. We set out to determine the prevalence and determinants of HPV infection among sexually active fishermen along Lake Victoria in the Kisumu district of Kenya. METHODS: Genital swabs were obtained from 250 consenting fishermen from 18 beaches and a detailed sociodemographic questionnaire was administered. HPV positivity was determined by polymerase chain reaction amplification and detected by dot blot hybridisation with generic HPV and beta-globin probes. HPV positive samples were genotyped using the Roche Linear array assay. RESULTS: Overall, 144 (57.6%) fishermen had detectable HPV DNA, 106 (42.4%) were infected with oncogenic HPV types, with HPV-16 being the most frequent type (12.4%). Among HPV positive men, 105 (72.9%) were infected with more than one HPV type and 20 (13.9%) were infected with more than six different types. HIV seropositive men (PR 1.49, 95% CI 1.19 to 1.86) and those divorced or separated (PR 1.62, 95% CI 1.13 to 2.33) were more likely to be infected with HPV. HIV infection (PR 1.22, 95% CI 1.01 to 1.47) was the only factor independently associated with infection with multiple types of HPV. CONCLUSION: The prevalence of oncogenic HPV infection is high among this population and is associated with HIV serostatus and marital status. This community could benefit from enhanced sexually transmitted infection and HIV prevention interventions.

HLA class II DR-DQ and increased risk of cervical cancer among Senegalese women.

To examine Senegalese women to confirm and extend associations between HLA class II types and cervical cancer previously observed among African-American, Caucasian, Hispanic, and Japanese ethnic populations, 55 Senegalese women with invasive cervical carcinoma were compared with age-matched (human papillomavirus) HPV-positive (n = 83) and HPV-negative (n = 107) control women. PCR-based HPV and HLA typing methods were used. Data were analyzed using a global randomization test and conditional logistic regression. Although this study failed to confirm a previously reported association between cervical cancer and DQB1*03 alleles, the DRB1*1101-DQB1*0301 haplotype was detected more frequently among cervical carcinoma cases than among controls (adjusted odds ratio, 2.6; 95% confidence interval, 1.0-7.1). Furthermore, as reported by others, we observed a negative association of borderline statistical significance between DRB1*13 and cervical carcinoma (adjusted odds ratio, 0.5; 95% confidence interval, 0.2-1.1). Observations from this study confirm earlier findings of a negative association between DRB1*13 and cervical cancer and suggest that specific DRB1-DQB1 haplotype combinations, rather than individual DQB1*03 alleles, increase the risk for cervical cancer.

Papanicolaou test screening and prevalence of genital human papillomavirus among women who have sex with women.

OBJECTIVES: The purpose of this study was to examine frequency of and attitudes toward Papanicolaou (Pap) test screening in women who have sex with women (WSW) and to determine prevalence of genital human papillomavirus (HPV). METHODS: Women were eligible if they reported having engaged in sex with another woman in the preceding year Medical and sexual histories were obtained. Cervical specimens for Pap tests and cervical and vaginal specimens for HPV DNA testing were collected. RESULTS: HPV DNA was detected in 31 of 248 WSW (13%). Women who had never had sex with men were less likely to have undergone pelvic examinations and had fewer recent Pap tests. Reasons for not undergoing Pap tests included lack of insurance, previous adverse experiences, and belief that Pap tests were unnecessary. CONCLUSIONS: Despite the occurrence of genital HPV, WSW do not receive adequate Pap test screening. Pap test screening recommendations should not differ for WSW, regardless of sexual history with men.

Characteristics of female sexually transmitted disease clinic clients who report same-sex behaviour.

Female STD clinic clients were categorized by report of sex partners' gender in the preceding 2 months and characterized with respect to HIV risk and STD diagnosis. Among 18,585 visits, 290 women (1.5%) reported sex exclusively with women, and 841 (4.5%) reported sex with both men and women. Relative to women reporting sex only with men, those reporting sex with both men and women reported more recent partners, sex with partners at high risk for HIV, injection drug and crack cocaine use, and exchange of sex for drugs or money. Women reporting sex exclusively with women more frequently reported prior sex with a bisexual man or an HIV-infected partner. Female STD clinic clients who report sex with both men and women may be at increased HIV risk relative to women reporting sex exclusively with men, and women who report sex only with women may be more likely to have had sex with men at high risk for HIV infection.

Multiple conformational epitopes are recognized by natural and induced immunity to the E7 protein of human papilloma virus type 16 in man.

The reactivity of sera from patients with cervical cancer with the E7 protein of human papilloma virus type 16 (HPV16) was estimated using a novel non-radioactive immunoprecipitation assay and four established protein- and peptide-based immunoassays. Six of 14 sera from patients with cervical cancer and 1 of 10 sera from healthy laboratory staff showed repeated reactivity with E7 in at least one assay. Four of the 7 reactive sera were consistently reactive in more than one assay, but only one was reactive in all four assays. Following immunization with E7, 2 of 5 patients with cervical cancer had increased E7-specific reactivity, measurable in one or more assays. No single assay was particularly sensitive for E7 reactivity, or predictive of cervical cancer. Mapping of E7 reactivity to specific E7 peptides was unsuccessful, suggesting that natural or induced E7 reactivity in human serum is commonly directed to conformational epitopes of E7. These results suggest that each assay employed in this study measures a different aspect of E7 reactivity, and that various reactivities to E7 may manifest following HPV infection or immunization. This finding is of significance for monitoring of E7 immunotherapy and for serological screening for cervical cancer.

Genital human papillomavirus infection in women who have sex with women: a review.

Sexual transmission of human papillomavirus between women has been postulated on the basis of reports of abnormal Papanicolaou smears in women who reported no prior sex with men and by studies using amplified deoxyribonucleic acid technology for human papillomavirus detection. To review the current knowledge of the epidemiology of human papillomavirus and the Papanicolaou smear screening practices among women who have sex with women, studies were identified from a search of the MEDLINE database from January 1980-June 1999. Several factors, including prior or concurrent sex with men and sexual behaviors between women, validate the possibility of human papillomavirus infection among women who have sex with women, and data support that human papillomavirus transmission also occurs. Limited data indicate that the frequency of routine Papanicolaou smear screening among women who have sex with women may be suboptimal relative to heterosexual women. Education of women who have sex with women and the providers of their health care should counter any assumptions that sex between women confers no risk of human papillomavirus transmission. Women who have sex with women should receive Papanicolaou smear screening in accord with current guidelines.

Concurrent and sequential acquisition of different genital human papillomavirus types.

Coinfection with multiple types of genital human papillomavirus (HPV) has been reported, but how frequently it occurs and whether prior infection with specific HPV types inhibits subsequent infection by related types are not known. To address this, 518 women were followed for an average of 2.9 years, and behavioral information and cervical and vulvovaginal swabs for HPV DNA assay were obtained at 4-month intervals. A polymerase chain reaction-based method was used to detect types frequently found in cervical cancers (HPV 16, 18, 31, and 45) and in genital warts (HPV 6 and 11). Concurrent acquisition of multiple types occurred more often than expected by chance. However, no 2 types were more or less likely to be acquired concurrently than any other 2 types. When considering sequential acquisition of HPV types, we found that risk of acquiring a new HPV type was not decreased among those with prior infection by a phylogenetically related or unrelated type (hazard ratio [95% confidence interval], 1.0 [0.4-3.0] and 1.3 [0.8-2.1], respectively).

Comparison of human papillomavirus types 16, 18, and 6 capsid antibody responses following incident infection.

The relationship between human papillomavirus (HPV) DNA in the genital mucosa and serum IgG to HPV-16, -18, and -6 was studied in a cohort of 588 college women. Among women with incident HPV infections, 59.5%, 54.1%, and 68.8% seroconverted for HPV-16, -18, or -6, respectively, within 18 months of detecting the corresponding HPV DNA. Transient HPV DNA was associated with a failure to seroconvert following incident HPV infection; however, some women with persistent HPV DNA never seroconverted. Antibody responses to each type were heterogeneous, but several type-specific differences were found: seroconversion for HPV-16 occurred most frequently between 6 and 12 months of DNA detection, but seroconversion for HPV-6 coincided with DNA detection. Additionally, antibody responses to HPV-16 and -18 were significantly more likely to persist during follow-up than were antibodies to HPV-6.

Detection of cervical antibodies to human papillomavirus type 16 (HPV-16) capsid antigens in relation to detection of HPV-16 DNA and cervical lesions.

A more sensitive luminescence immunoassay (LIA) for human papillomavirus type 16 (HPV-16) was developed and used to measure HPV-16 antibodies in cervical samples from 292 college-aged women who were examined at 4-month intervals. Of the 609 collected samples, IgG, IgA, and secretory piece-associated antibodies to HPV-16 were detected in 12%, 6%, and 8%, respectively, of samples tested. Cervical IgG antibodies were most strongly associated with HPV-16 DNA detected within the previous 12 months (odds ratio, 3.3; 95% confidence interval, 1.4-7.8). Secretory IgA (cervical IgA- and secretory piece-positive) was most strongly associated with detection of a squamous intraepithelial lesions 4-8 months earlier (odds ratio, 6.4; 95% confidence interval, 1.9-21.8). As with serum HPV-16 antibodies, there appears to be a several-month delay between cervical HPV infection and detection of cervical antibodies.

Comparison of variant-specific hybridization and single-strand conformational polymorphism methods for detection of mixed human papillomavirus type 16 variant infections.

PCR-based variant-specific hybridization (VSH) and single-strand conformational polymorphism (SSCP) analyses were compared for their capacities to detect mixed human papillomavirus type 16 (HPV-16) variant infections within clinical specimens. The SSCP assay used in this comparison targets a 682-bp fragment that spans nucleotides 7445 to 222 within the HPV-16 genome. This fragment includes portions of the HPV-16 long control region and the E6 open reading frame and identifies three categories of SSCP patterns: those identical to the patterns of prototype HPV-16 (P), those identical to the patterns of Caski-derived HPV-16 (C), or those that are different from the P and C HPV-16 patterns and that are therefore classified as belonging to novel (N) HPV-16 variants. VSH targets the entire HPV-16 E6-coding region (nucleotides 56 to 640) and distinguishes previously described variant nucleotides at positions 109, 131, 132, 143, 145, 178, 286, 289, 350, 403, and 532. Clinical samples used in VSH and SSCP analyses were subjected to multiple independent amplification reactions. The resultant amplicons were cloned, and 14 to 78 clones per clinical specimen were evaluated by VSH. VSH detected an HPV-16 variant that represented at least 20% of the amplified HPV-16 variant population. In contrast, SSCP analysis detected HPV-16 variants that represented 36% of the amplified HPV-16 population. Comparison studies were conducted with mixed HPV-16 variant laboratory constructs. Again, VSH had a higher sensitivity than SSCP analysis in detecting mixed HPV-16 variant infections in these constructed amplicon targets. Accurate detection of HPV-16 variants may enhance our understanding of the natural history of HPV-16 infections.

Risk factors for HIV-1 shedding in semen.

Semen is the body fluid most commonly associated with sexual transmission of human immunodeficiency virus type-1 (HIV-1). Because the male genitourinary tract is distinct immunologically from blood, compartment-dependent factors may determine HIV-1 shedding in semen. To identify these factors, the authors obtained 411 semen and blood specimens from 149 men seen up to three times. Seminal plasma was assayed for HIV-1 RNA and semen was cocultured for HIV-1 and cytomegalovirus (CMV), which may up-regulate HIV-1 replication. The best multivariate model for predicting a positive semen HIV-1 coculture included two local urogenital factors, increased seminal polymorphonuclear cell count (odds ratio (OR) = 12.6 for each log10 increase/mL, 95% confidence interval (CI) 12.2, 134.5) and a positive CMV coculture (OR = 3.0, 95% CI 1.2, 7.7). The best multivariate model for predicting semen HIV-1 RNA included two systemic host factors, CD4+ cell counts <200/microliter (OR = 3.0, 95 percent CI 1.3, 6.9) and nucleoside antiretroviral therapy (monotherapy: OR = 0.5, 95% CI 0.3, 1.0; combination therapy: OR = 0.4, 95% CI 0.2, 0.9), and a positive CMV coculture (OR = 1.7, 95% CI 1.0, 3.0). Thus, both systemic and local genitourinary tract factors influence the risk of semen HIV-1 shedding. These findings suggest that measures of systemic virus burden alone may not predict semen infectivity reliably.

Clinical features of Chlamydia trachomatis rectal infection by serovar among homosexually active men.

BACKGROUND AND OBJECTIVES: Because C. trachomatis serovars correlate with the clinical manifestations of cervical infection, we undertook this study to determine whether clinical, behavioral, and laboratory findings correlate with C. trachomatis serovars isolated from rectal infections. GOAL OF THIS STUDY: To correlate C. trachomatis serovar with signs and symptoms of rectal infection. STUDY DESIGN: A cross-sectional study of 454 men with rectal C. trachomatis infection attending an urban sexually transmitted disease (STD) clinic was undertaken. Isolates were thawed, passaged to high titer, and typed using a panel of monoclonal antibodies. Compared to men infected with B complex isolates (164), men with C complex isolates (55) were less likely to report symptoms (OR: 0.4; 95% CI: 0.1-0.8), or to have erythema, bleeding, or mucopus (OR: 0.3; 95% CI: 0.1-0.8). Among men with inclusion counts of more than 100, those infected with FG group versus B complex isolates were more likely to present with mucopus (OR: 10.5; 95% CI: 1.2-95.5), more than 15 polymorphonuclear leukocytes (OR: 19.2; 95% CI: 1.7-219.8), and proctitis (OR: 4.2; 95% CI: 1.1-16.7). CONCLUSION: Signs and symptoms of rectal infection correlate with the serovar of C. trachomatis isolates.

A matched prospective study of human immunodeficiency virus serostatus, human papillomavirus DNA, and cervical lesions detected by cytology and colposcopy.

OBJECTIVE: To compare the prevalence and type of human papillomavirus (HPV) infections in the genital tract of human-immunodeficiency-virus- (HIV) seropositive and -seronegative women matched for cytology and to examine prospectively the relationship of HPV DNA, colposcopic findings and cervical squamous intraepithelial lesions (SIL) in these matched seropositive and seronegative cohorts. METHODS: A matched prospective study of HIV-seropositive and -seronegative women undergoing cytologic screening, colposcopy, and testing for HPV DNA and other infections at each visit. RESULTS: Twenty-three HIV-seropositive women were matched with 23 seronegative women by cervical cytology reading, lifetime number of sexual partners, age, and follow-up length. Fourteen pairs of these women had follow-up visits every 4 months, for 56 and 53 total visits in seropositive and seronegative women, respectively. After matching, the groups had a similar overall prevalence of HPV DNA and of HPV oncogenic (high risk) types at baseline. On follow up, HIV-seropositive women were more likely than seronegative women to develop SIL (38% vs. 10%), less likely to have negative cytology (34% vs. 60%, overall P = 0.03), more visits with HPV DNA detected (68% vs. 40% P = 0.04), and more visits with multiple HPV DNA types detected (18% vs. 0%, P = 0.02). Colposcopic lesions in the seropositive women were more likely to have sharp borders or mosaicism or to be thick white (P = 0.009). CONCLUSIONS: After matching for baseline Papanicolaou smear readings, these data suggest that over time seropositive women have more visits that yield abnormal cytology, more persistent HPV DNA detection, and more colposcopic abnormalities than seronegative women.

A case-control study of necrotizing fasciitis during primary varicella.

OBJECTIVE: An increase in the incidence of necrotizing fasciitis (NF) occurring in previously healthy children with primary varicella was noted in the Washington State area between December 1993 and June 1995. Our objective was to investigate ibuprofen use and other risk factors for NF in the setting of primary varicella. METHODS: Case-control study. Demographic information, clinical parameters, and potential risk factors for NF were compared for cases and controls. Cases of NF were analyzed to identify potential determinants of NF complicated by renal insufficiency and/or streptococcal toxic shock syndrome. Multivariate logistic regression was used to evaluate the association between ibuprofen use and NF. A case was defined as a child with NF hospitalized within 3 weeks of primary varicella (n = 19). Controls were children hospitalized with a soft tissue infection other than NF within 3 weeks of primary varicella (n = 29). Odds ratios (ORs) of ibuprofen, as well as other potential risk factors were evaluated. In addition, demographic and clinical data as well as other potential risk factors were compared between cases and controls. RESULTS: After controlling for gender, age, and group A streptococcus isolation, cases were more likely than controls to have used ibuprofen before hospitalization (OR, 11. 5; 95% confidence interval, 1.4 to 96.9). In most children, ibuprofen was initiated after the onset of symptoms of secondary infection. Children with NF complicated by renal insufficiency and/or streptococcal toxic shock syndrome were more likely than children with uncomplicated NF to have used ibuprofen (OR, 16.0; 95% confidence interval, 1.0 to 825.0). Children with complicated NF also had a higher mean maximum temperature (40.9 degrees C vs 39.3 degrees C), and a longer mean duration of secondary symptoms (1.7 days vs 0.6 days) before admission than children with uncomplicated NF. CONCLUSION: Ibuprofen use was associated with NF in the setting of primary varicella. Additional studies are needed to establish whether ibuprofen use has a causal role in the development of NF and its complications during varicella.

Effect of trimethoprim-sulfamethoxazole as Pneumocystis carinii pneumonia prophylaxis on bacterial illness, Pneumocystis carinii pneumonia, and death in persons with AIDS.

To measure the effect of trimethoprim-sulfamethoxazole (TMP-SMX) in preventing bacterial illness, Pneumocystis carinii pneumonia (PCP), and death in people with AIDS, we conducted a retrospective medical record review of 1078 persons who were observed for 3 years on average who attended nine outpatient facilities in Seattle, Washington between January 1990 and April 1996. We calculated relative risk estimates to measure the protective effect of TMP-SMX on the development of major bacterial illnesses, PCP, and death. Use of TMP-SMX decreased the risk of PCP (relative risk [RR] = 0.23; 95% confidence interval [CI], 0.14-0.36) and deaths not attributable to PCP (RR = 0.59; 95% CI, 0.47-0.73). Prevention of major bacterial illnesses of known etiology was of borderline significance (RR = 0.77; 95% CI, 0.57-1.05) and became statistically significant with the addition of patients with infections of unknown etiology (RR = 0.77; 95% CI 0.61-0.97). Use of TMP-SMX PCP prophylaxis significantly reduced the risks of death and of PCP and was associated with a trend toward reduced risk of major bacterial infections.

Genital human papillomavirus infection in women who have sex with women.

Genital infection with human papillomavirus (HPV), as determined by polymerase chain reaction detection of HPV DNA and prevalence of HPV-6 and -16 serum antibodies, was investigated in 149 women who were sexually active with women. By use of HPV L1 consensus primers and hybridization to types 6/11, 16, 18, 31/33/35/39, and 45 and a generic probe, HPV DNA was detected in 30% of subjects; of these, 20% had type 31/33/35/39, 18% had type 16, and 2% had type 6/11. Of 21 subjects reporting no prior sex with men, HPV DNA was detected in 19% and squamous intraepithelial lesions in 14%. By capture ELISA with HPV-6 and -16 L1 capsids, 47% of subjects were seropositive for HPV-16 and 62% for HPV-6. Current smoking was associated with detectable HPV DNA. Genital HPV infection and squamous intraepithelial lesions are common among women who are sexually active with women and occur among those who have not had sex with men.

Vulvovaginal candidiasis: clinical manifestations, risk factors, management algorithm.

OBJECTIVE: To correlate symptoms, signs, and risk factors with positive wet mounts or cultures for Candida albicans and to develop an algorithm to diagnose vulvovaginal candidiasis. METHODS: This cross-sectional study of 774 randomly selected women from an urban sexually transmitted disease (STD) clinic evaluated symptoms, signs, and risk factors associated with C albicans, detected by wet mount and culture, and constructed an algorithm. RESULTS: C albicans, recovered from 186 (24%) of the 774 women, was associated with chief complaints of vulvar pruritus or burning. Elicited symptoms were vulvar pruritus, pain or burning, and external dysuria; signs were vulvar erythema, edema, fissures, vaginal erythema, and thick, curdy vaginal discharge. Among 545 women with symptoms of either increased vaginal discharge or vulvar pruritus or burning, only 155 (28%) had positive C albicans cultures, whereas bacterial vaginosis or other sexually transmitted infections were found in 288 (53%). In multivariate analysis, risk factors for positive C albicans culture included condom use, presentation after the 14th menstrual cycle day, sexual intercourse more than four times per month, recent antibiotic use, young age, past gonococcal infection, and absence of current gonorrhea or bacterial vaginosis. A clinical algorithm based on symptoms, signs, and selective use of wet mounts and cultures would have provided prompt treatment to 150 of 167 (90%) women with vulvovaginal candidiasis while minimizing the number of cultures performed. CONCLUSION: A simple algorithm using symptoms, signs, wet mounts, and selective cultures can identify 90% of women with vulvovaginal candidiasis. In this STD clinic, vulvovaginal symptoms also require assessment for bacterial vaginosis, trichomoniasis, and cervical infection.

Use of hospital services by AIDS patients with psychiatric illness.

The purpose of this study was to assess the effect of psychiatric illness on length of stay and patterns of admission among AIDS patients hospitalized for medical illnesses. Medical records were abstracted for AIDS patients admitted to hospitals in Washington State from 1990 through 1992. Psychiatric comorbidity was defined by the presence of an International Classification of Disease-9 code reflecting psychiatric illness. Medical morbidity was addressed using CD4 count and AIDS-defining illnesses as markers of disease severity. Of 2834 admissions, 15% included one or more psychiatric diagnoses. Psychiatric illness (F 39.1; df 1,2830; p < 0.001) and discharge disposition (F 81.2; df 2,2830; p < 0.001) contributed significantly to the model, explaining increased length of stay (F 67.2; df 3,2830; p < 0.001). Future research needs to address the possible etiology of psychiatric comorbidity's contribution to length of stay and the effect on quality and cost of care.

Risk of anal carcinoma in situ in relation to human papillomavirus type 16 variants.

Infection with human papillomavirus (HPV), especially HPV16, is central to the development of squamous anogenital cancers and their precursor lesions, termed "squamous intraepithelial neoplasias." Men who have sex with men, particularly those who are infected with HIV, are at a high risk for anal infection with HPV16 and for low-grade anal neoplasia; however, only a subset of these men develop anal invasive cancer or its immediate precursor lesion, anal carcinoma in situ (CIS). To examine the hypothesis that certain variants of HPV16 are most strongly associated with development of anal CIS, we followed 589 men who have sex with men whose initial anal cytological smears did not show anal CIS. Anoscopy, anal cytology, and PCR-based assays for detection and classification of HPV types were performed every 4-6 months, with HPV16 further classified by single-stranded conformation polymorphism analysis as being a prototype-like (PL) or non-prototype-like (NPL) variant. Anal CIS was histologically confirmed in 6 of 384 (1.6%) consistently HPV16-negative men, in 12 of 183 (6.6%) men with HPV16 PL variants, and in 4 of 22 (18.2%) men with HPV16 NPL variants. After adjustment for anal cytological diagnoses at study entry, HIV status and CD4 count, and detection of HPV types other than type 16, men with HPV16 NPL variants were 3.2 times (95% confidence interval, 1.0-10.3) more likely to develop anal CIS than were those with PL variants. Neither detection of HPV16 DNA at high levels nor detection of HPV16 DNA for a prolonged period, factors that we previously demonstrated to be associated with risk of high-grade anal squamous intraepithelial neoplasia, was significantly associated with HPV16 NPL variants. The biological mechanism relating to Ihis excess risk remains undetermined.