Our aim was to determine if (1) Hybrid Capture 2 and a PCR-based method were comparable for detection of high-risk HPVs, (2) clinician-collected and self-collected samples were equally efficient to detect HPV and cervical cancer precursor lesions and (3) if participation rates improved with home-based vs. clinic-based self collection.
Samples were selected from women participating in a cervical cancer screening study according to human papillomavirus (HPV), visual inspection with acetic acid (VIA), or Pap smear screening results. From 432 of 892 selected women, split sample aliquots were tested for HPV DNA using both the Hybrid Capture 2 assay and the Roche prototype line blot assay. Women from a subset of villages were recruited at two separate time points for clinic-based self-collection and home-based self-collection, and participation rates were compared.
Pairwise agreement between self- and clinician-collected samples was high by both hc2 (90.8% agreement, kappa=0.7) and PCR (92.6% agreement, kappa=0.8), with significantly increased high-risk HPV detection in clinician-collected specimens (McNemar's p<0.01). Ability to detect precursor lesions was highest by PCR testing of clinician-collected samples and lowest by Hybrid Capture 2 testing of self-collected samples (11/11 and 9/11 cases of cervical intraepithelial neoplasia grade 2/3 and cancer detected, respectively). Participation in home-based screening was significantly higher than clinic-based screening (71.5% and 53.8%, respectively; p<0.001) among women 30-45 years old.
The combination of improved screening coverage and a high single test sensitivity afforded by HPV DNA testing of home-based self-collected swabs may have a greater programmatic impact on cervical cancer mortality reduction compared to programs requiring a pelvic exam.
The discovery that certain high-risk strains of human papillomavirus (HR-HPV) cause nearly 100% of invasive cervical cancer has spurred a revolution in cervical cancer prevention by promoting the development of viral vaccines. Although the efficacy of these vaccines has already been demonstrated, a complete understanding of viral latency and natural immunity is lacking, and solving these mysteries could help guide policies of cervical cancer screening and vaccine use. Here, we examine the epidemiological and biological understanding of the natural history of HPV infection, with an eye toward using these studies to guide the implementation of cervical cancer prevention strategies.
Background. Cohort effects, new sex partnerships, and
human papillomavirus (HPV) reactivation have been posited as explanations for the bimodal
age-specific HPV prevalence observed in some populations; no studies have systematically
evaluated the reasons for the lack of a second peak in the United States.
Methods. A cohort of 843 women aged 35–60 years
were enrolled into a 2-year, semiannual follow-up study. Age-specific HPV prevalence was
estimated in strata defined by a lower risk of prior infection (<5 self-reported
lifetime sex partners) and a higher risk of prior infection (≥5 lifetime sex partners).
The interaction between age and lifetime sex partners was tested using likelihood ratio
statistics. Population attributable risk (PAR) was estimated using Levin's
Results. The age-specific prevalence of 14 high-risk
HPV genotypes (HR-HPV) declined with age among women with <5 lifetime sex partners but
not among women with ≥5 lifetime sex partners (P = .01 for
interaction). The PAR for HR-HPV due to ≥5 lifetime sex partners was higher among older
women (87.2%), compared with younger women (28.0%). In contrast, the PAR
associated with a new sex partner was 28% among women aged 35–49 years and
7.7% among women aged 50–60 years.
Conclusions. A lower cumulative probability of HPV
infection among women with a sexual debut before the sexual revolution may be masking an
age-related increase in HPV reactivation in the United States.
Human Papillomavirus; menopause; perimenopause; sexual revolution; cervical cancer; reactivation; cohort effect; age
Anne Rositch and colleagues discuss the study by Peter Sasieni and colleagues on cervical cancer screening in older women and describe the further information needed to help inform decisions about whether to extend screening programs beyond 65 years for women with adequate negative screening.
Please see later in the article for the Editors' Summary
We explored the age-stratified correlates and correlations between HR-HPV infection and cervical abnormalities in perimenopausal women.
Materials and methods
HPV testing and Pap smear screening were performed at baseline on 841 routinely screened women age 35–60 years in the HPV in Perimenopause (HIP) cohort. Demographic, behavioral and medical information was collected through telephone administered questionnaires. Descriptive analyses were used to examine the correlation between HR-HPV infection and cervical abnormalities by age. Logistic regression was used to determine correlates of HPV and abnormalities in women under and over 45 years of age.
The prevalence of HPV, HR-HPV and cervical abnormalities decreased significantly with increasing age, as did the correlation between HR-HPV and cervical abnormalities. The prevalence of HR-HPV was 50% among younger women with abnormalities but this decreased steadily to 20% HR-HPV detection among 50–54 year old, and no abnormalities were detected in 55–60 year old women. Different correlates of HR-HPV infection and abnormalities were observed in women ≥45 years, a pattern not seen in the younger women.
Although the relative proportion of low and high-grade abnormalities did not change with age, we saw a loss of concordance between HR-HPV detection and cytological abnormalities with increasing age. Current guidelines for cervical cancer screening group together all women age 30 and above. Our data raise important questions about the interpretation of HPV and Pap test results in this age group and suggest that ongoing surveillance of HPV and cytology in cervical cancer screening programs consider a third age stratification among older women.
perimenopausal women; menopause; human papillomavirus; HPV; cervical lesions; cytology; cervical cancer; screening; guidelines
Understanding the fraction of newly detected human papillomavirus (HPV) infections due to acquisition and reactivation has important implications on screening strategies and prevention of HPV-associated neoplasia. Information on sexual activity and cervical samples for HPV DNA detection using Roche Linear Array were collected semi-annually for two years from 700 women age 35–60 years. Incidence and potential fraction of HPV infections associated with new and lifetime sexual partnerships were estimated using Poisson models. Cox frailty models were used to estimate hazard ratios (HR) for potential risk factors of incident HPV detection. Recent and lifetime numbers of sexual partners were both strongly associated with incident HPV detection. However, only 13% of incident detections were attributed to new sexual partners whereas 72% were attributed to ≥5 lifetime sexual partners. Furthermore, 155 out of 183 (85%) incident HPV detections occurred during periods of sexual abstinence or monogamy, and were strongly associated with cumulative lifetime sexual exposure (HR: 4.1, 95% CI: 2.0, 8.4). This association increased with increasing age. These data challenge the 20 paradigm that incident HPV detection is driven by current sexual behavior and new viral acquisition in older women. Our observation that most incident HPV infection was attributable to past, not current, sexual behavior at older ages supports a natural history model of viral latency and reactivation. As the highly exposed baby-boomer generation of women with sexual debut after the sexual revolution transition to menopause, the implications of HPV reactivation at older ages on cervical cancer risk and screening recommendations should be carefully evaluated.
human papillomavirus; HPV; sexual behavior; older women; reactivation; incidence; acquisition; perimenopause; aging
papillomavirus infections; HIV; meta-analysis; human papillomavirus; risk factors
Ophthalmic sponges are used to collect undiluted cervical secretions for assessment of markers of genital tract immunity. Heterogeneity in absorbed and extracted sample volumes requires normalization in order to make valid inter-individual comparisons. We evaluated the performance of adjustment by weight and total protein on normalizing inter-individual variability of immune marker measurement due to differences in volume collection. Normalization to total protein resulted in a minimal loss of usable specimens and a significant reduction in the correlation of immune marker concentration to specimen weight compared to weight adjustment. Total protein normalization appeared to be more effective than weight adjustment in reducing the dependence of cervical immune marker concentrations on differences in specimen volume.
Cytokines; Cervical secretions; Ophthalmic sponges; Weight adjustment; Protein adjustment
Women ≥45 years of age with persistent HPV infections have distinct peripheral circulating immune profiles. Few studies have comprehensively evaluated the cervical immunologic microenvironment in HPV-positive and HPV-negative perimenopausal women.
We collected cervical secretion specimens from 34 high risk HPV (HR-HPV) positive and 44 HR-HPV negative women enrolled in an ongoing prospective cohort assessing the natural history of HPV across the menopausal transition. We used these specimens to quantify concentrations of 27 different immune markers using multiplexed bead-based immunoassays.
HR-HPV positive women had significantly higher median concentrations of IL-5 (0.11 ng/mgtotal protein vs. 0.08 ng/mgtotal protein), IL-9 (2.7 ng/mgtotal protein vs. 2.1 ng/mgtotal protein), IL-13 (2.1 ng/mgtotal protein vs. 0.9 ng/mgtotal protein), IL-17 (2.9 ng/mgtotal protein vs. 1.1 ng/mgtotal protein), EOTAXIN (4.1 ng/mgtotal protein vs. 1.1 ng/mgtotal protein), GM-CSF (4.3 ng/mgtotal protein vs. 3.3 ng/mgtotal protein), and MIP-1α (3.5 ng/mgtotal protein vs. 1.9 ng/mgtotal protein) compared to HR-HPV negative women. A shift in the correlation of T-cell and pro-inflammatory cytokines (IFN-γ, IL-5, IL-9, IL-10, IL-12, IL-13, IL-15, and TNF-α) from IL-2 to EOTAXIN was observed between HR-HPV negative and positive women.
Higher local concentrations of anti-inflammatory and allergy associated markers, with a shift in T-cell associated cytokine correlation from IL-2 to EOTAXIN, are associated with HPV infection among older women.
Human papillomavirus; Interleukin-2; EOTAXIN; Menopause
The prevalence of HPV is higher among HIV+ women, but the prevalence of HPV prior to HIV acquisition has not been carefully evaluated.
This study evaluated whether HPV infection is independently associated with heterosexual HIV acquisition in a cohort of Zimbabwean women.
Case-control study nested within a large multi-center cohort study (HC-HIV).
Cases consisted of Zimbabwean women with incident HIV infection observed during follow-up (n=145). HIV-uninfected controls were selected and matched to cases (n=446). The prevalence of cervical HPV infections was compared at the visit prior to HIV infection in the cases and at the same follow-up visit in the matched controls.
The odds of acquiring HIV were 2.4 times higher in women with prior cervical HPV infection after adjustment for behavioral and biologic risk factors. There was no statistically significant difference in the risk of HIV acquisition between women infected with high versus low risk HPV types. Loss of detection of at least one HPV DNA type was significantly associated with HIV acquisition (OR =5.4 [95%CI, 2.9–9.9] (p<.0001).
Cervical HPV infection is associated with HIV acquisition among women residing in a region with a high prevalence of both infections. Further studies are required to evaluate whether the observed association is causal.
HPV; heterosexual HIV transmission; HIV prevention; cervical HPV; STI
High-risk human papillomavirus (HPV) infections are necessary but insufficient causes of cervical cancers. Other risk factors for cervical cancer (e.g., pregnancy, smoking, infections causing inflammation) can lead to high and sustained nitric oxide (NO) concentrations in the cervix, and high NO levels are related to carcinogenesis through DNA damage and mutation. However, the effects of NO exposure in HPV-infected cells have not been investigated. In this study, we used the NO donor DETA-NO to model NO exposure to cervical epithelium. In cell culture media, 24-hour exposure to 0.25 to 0.5 mmol/L DETA-NO yielded a pathologically relevant NO concentration. Exposure of cells maintaining episomal high-risk HPV genomes to NO increased HPV early transcript levels 2- to 4-fold but did not increase viral DNA replication. Accompanying increased E6 and E7 mRNA levels were significant decreases in p53 and pRb protein levels, lower apoptotic indices, increased DNA double-strand breaks, and higher mutation frequencies when compared with HPV-negative cells. We propose that NO is a molecular cofactor with HPV infection in cervical carcinogenesis, and that modifying local NO cervical concentrations may constitute a strategy whereby HPV-related cancer can be reduced.
To determine human papillomavirus (HPV) types by polymerase chain reaction (PCR)-reverse line blot assay and examine the concordance between HPV by Hybrid Capture 2 (HC2) and PCR on self-collected vaginal and physician-collected cervical samples and cytology.
This was a cross-sectional study of 546 sexually active women aged ≥30 years with persistent vaginal discharge, intermenstrual or postcoital bleeding or an unhealthy cervix. Participants self-collected vaginal samples (HPV-S) and physicians collected cervical samples for conventional Pap smear and HPV DNA (HPV-P) testing and performed colposcopy, with directed biopsy, if indicated. HPV testing and genotyping was done by HC2 and PCR reverse line blot assay. Concordance between HC2 and PCR results of self- and physician-collected samples was determined using a Kappa statistic (κ) and Chi-square test.
Complete data were available for 512 sets with 98% of women providing a satisfactory self-sample. PCR detected oncogenic HPV in 12.3% of self- and 13.0% of physician-collected samples. Overall, there was 93.8% agreement between physician-collected and self-samples (κ = 76.31%, 95% confidence interval [CI]: 64.97–82.29%, p = 0.04)—complete concordance in 473 cases (57 positive, 416 negative), partial concordance in seven pairs and discordance in 32 pairs. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of self-sampling for detection of cervical intraepithelial neoplasia (CIN)2+ disease were 82.5%, 93.6%, 52.4% and 98.4%, respectively; for physician-sampling they were 87.5%, 93.2%, 52.2% and 98.9%, respectively; and for cytology they were 77.5%, 87.3%, 34.1% and 97.9%, respectively. Concordance between HC2 and PCR was 90.9% for self-samples (κ = 63.7%, 95% CI: 55.2–72.2%) and 95.3% for physician-collected samples (κ = 80.4%, 95% CI: 71.8–89.0%).
Self-HPV sampling compares favourably with physician-sampling and cytology. A rapid, affordable, HPV self-test kit can be used as the primary method of cervical cancer screening in low-resource situations.
HPV types; Self-sampling; Screening; Hybrid Capture 2; PCR; CIN; Genotyping
Even in the era of highly effective HPV prophylactic vaccines, substantial reduction in worldwide cervical cancer mortality will only be realized if effective early detection and treatment of the millions of women already infection and the millions who may not receive vaccination in the next decade can be broadly implemented through sustainable cervical cancer screening programs. Effective programs must meet three targets: 1) at least 70% of the targeted population should be screened at least once in a lifetime, 2) screening assays and diagnostic tests must be reproducible and sufficiently sensitive and specific for the detection of high-grade precursor lesions (i.e., CIN2+), and 3) effective treatment must be provided. We review the evidence that HPV DNA screening from swabs collected by the women in their home or village is sufficiently sound for consideration as a primary screening strategy in the developing world, with sensitivity and specificity for detection of CIN2+ as good or better than Pap smear cytology and VIA. A key feature of a self-collected HPV testing strategy (SC-HPV) is the move of the primary screening activities from the clinic to the community. Efforts to increase the affordability and availability of HPV DNA tests, community education and awareness, development of strong partnerships between community advocacy groups, health care centers and regional or local laboratories, and resource appropriate strategies to identify and treat screen-positive women should now be prioritized to ensure successful public health translation of the technologic advancements in cervical cancer prevention.
The species Alphapapillomavirus 7 (alpha-7) contains human papillomavirus genotypes that account for 15% of invasive cervical cancers and are disproportionately associated with adenocarcinoma of the cervix. Complete genome analyses enable identification and nomenclature of variant lineages and sublineages.
The URR/E6 region was sequenced to screen for novel variants of HPV18, 39, 45, 59, 68, 70, 85 and 97 from 1147 cervical samples obtained from multiple geographic regions that had previously been shown to contain an alpha-7 HPV isolate. To study viral heterogeneity, the complete 8 kb genome of 128 isolates, including 109 sequenced for this analysis, were annotated and analyzed. Viral evolution was characterized by constructing phylogenic trees using maximum-likelihood and Bayesian algorithms. Global and pairwise alignments were used to calculate total and ORF/region nucleotide differences; lineages and sublineages were assigned using an alphanumeric system. The prototype genome was assigned to the A lineage or A1 sublineage.
The genomic diversity of alpha-7 HPV types ranged from 1.1% to 6.7% nucleotide sequence differences; the extent of genome-genome pairwise intratype heterogeneity was 1.1% for HPV39, 1.3% for HPV59, 1.5% for HPV45, 1.6% for HPV70, 2.1% for HPV18, and 6.7% for HPV68. ME180 (previously a subtype of HPV68) was designated as the representative genome for HPV68 sublineage C1. Each ORF/region differed in sequence diversity, from most variable to least variable: noncoding region 1 (NCR1) / noncoding region 2 (NCR2) > upstream regulatory region (URR) > E6 / E7 > E2 / L2 > E1 / L1.
These data provide estimates of the maximum viral genomic heterogeneity of alpha-7 HPV type variants. The proposed taxonomic system facilitates the comparison of variants across epidemiological and molecular studies. Sequence diversity, geographic distribution and phylogenetic topology of this clinically important group of HPVs suggest an independent evolutionary history for each type.
High-risk human papillomavirus (HR-HPV) infection is the most common sexually transmitted infection. Penile and cervical cancer rates are highest in sub-Saharan Africa. However, little is known about the impact of HIV infection on HR-HPV acquisition and clearance among heterosexual men.
HR-HPV incidence and clearance were evaluated in 999 men (776 HIV-negative and 223 HIV-positive) aged 15–49 who participated in male circumcision trials in Rakai, Uganda.
Penile swabs were tested for HR-HPV by Roche HPV Linear Array. A Poisson multivariable model was used to estimate adjusted incidence rate ratios (adjIRR) and clearance risk ratios (adjRR).
HR-HPV incidence was 66.5/100 py in HIV-positive men and 32.9/100 py among HIV-negative men (IRR=2.0, 95%CI 1.7–2.4). Incidence was higher with non-marital status (adjIRR=1.7, 95%CI 1.2–2.5), and decreased with age (adjIRR=0.6, 95%CI 0.4–1.0) and male circumcision (adjIRR=0.7, 95%CI 0.6–0.9). HR-HPV clearance was 114.7/100 py for HIV-positive men and 170.2/100 py for HIV-negative men (RR=0.7, 95%I 0.6–0.8). Clearance in HIV-negative men was increased with circumcision (adjRR=1.5, 95%CI 1.3–1.7), HSV-2 infection (adjRR=1.2, 95%CI 1.0–1.4), and symptoms of urethral discharge (adjRR=1.4, 95%CI 1.1–1.7).
HR-HPV is common among heterosexual Ugandan men, particularly the HIV-infected. HIV infection increases HR-HPV acquisition and reduces HR-HPV clearance. Promotion of male circumcision and HPV vaccination is critical in sub-Saharan Africa.
Human papillomavirus (HPV); HIV; male circumcision; Uganda
The burden of cervical cancer is disproportionately high in low-resource settings. With limited implementation of human papillomavirus (HPV) vaccines on the horizon in the developing world, reliable data on the epidemiology of high-risk HPV (HR-HPV) infection in distinct geographic populations is essential to planners of vaccination programs. The purpose of this study was to determine whether urban patterns of HR-HPV occurrence can be generalized to rural areas of the same developing country, using data from Mali, West Africa, as an example.
Urban and rural women in Mali participated in a structured interview and clinician exam, with collection of cervical samples for HPV DNA testing, to determine HR-HPV prevalence and correlates of infection. Correlates were assessed using bivariate analysis and logistic regression.
A total of 414 women (n=202 urban women; n=212 rural women) were recruited across both settings. The prevalence of HR-HPV infection in rural women was nearly twice that observed in urban women (23% v. 12%). Earlier age of sexual debut and fewer pregnancies were associated with HR-HPV infection among urban women, but not rural women. Twenty-six percent of urban women who had sexual intercourse by age 14 had an HR-HPV infection, compared to only 9% of those who had later sexual debut (p<0.01). Overall, age, income, and polygamy did not appear to have a relationship with HR-HPV infection.
Compared to urban women, rural women were significantly more likely to be infected with high-risk HPV. The patterns and risk factors of HR-HPV infection may be different between geographic areas, even within the same developing country. The high prevalence in both groups suggests that nearly all rural women and most urban women in Mali will be infected with HR-HPV during their lifetime, so the effects of risk factors may not be statistically apparent. To control HPV and cervical cancer in West Africa and the rest of the developing world, planners should prioritize vaccination in high-burden areas.
Uterine cervical cancer; Reproductive health; HPV prevalence; Mali
There are no data available on human papillomavirus (HPV) infections in women living in the Mississippi Delta, where cervical cancer incidence and mortality among African American women is among the highest in the United States. The aim of this analysis was to report the age-specific prevalence of HPV in this population.
We recruited 443 women, 26–65 years of age, from the general population of women living in the Mississippi Delta to participate; 252 women had been screened for cervical cancer within the last 3 years while 191 had not. Women underwent a pelvic exam and had clinician-collected Pap sample taken for the routine cervical cancer screening by cytology. Women were asked to collect a self-collected specimen at home and return it to the clinic. Both specimens were tested for HPV genotypes.
Four hundred and six women (91.6%) had HPV genotyping results for the clinician-collected and self-collected specimens. The prevalence of carcinogenic HPV was 18.0% (95% CI: 14.4%-22.1%) for clinician-collected specimens and 26.8% (95% CI: 22.6%-31.4%) for self-collected specimens. The concordance for the detection of carcinogenic HPV between clinician-collected and self-collected specimens was only fair (kappa = 0.54). While the prevalence of carcinogenic HPV in either sample decreased sharply with increasing age (ptrend< 0.01), the prevalence of non-carcinogenic HPV did not, especially the prevalence of HPV genotypes in the alpha 3/4/15 phylogenetic group.
The prevalence of carcinogenic HPV in our sample of women living in the Mississippi Delta was greater than the prevalence reported in several other U.S. studies. The high carriage of HPV infection, along with lack of participation in cervical cancer screening by some women, may contribute to the high cervical cancer burden in the region.
Human papillomavirus (HPV); Self-collection; Pap; Cervical intraepithelial neoplasia; Cervix
Objective: Cervical cancer is a leading cause of cancer mortality in South Africa. However, little is known about oral human papillomavirus (HPV) infection in high human immunodeficiency virus (HIV) seroprevalence settings.
Method: Thirty-four adult heterosexual couples attending an HIV testing center in Soweto, South Africa were enrolled. Each participant provided an oral rinse sample and genital swab, which were tested for 37 types of HPV DNA, and completed a risk behavior survey.
Results: Median age was 31 years and 9% (3/34) of men and 29% (10/34) of women enrolled tested HIV-positive; median CD4 count was 437 cells/mm3. Oral HPV prevalence was similar in women and men (12 vs. 18%, p = 0.48), and was non-significantly higher in HIV-infected vs. HIV-uninfected (23 vs. 13%, p = 0.34) subjects. Most men (82%) and women (84%) reported ever performing oral sex. Median number of lifetime sexual partners was “2–5” while median number of lifetime oral sex partners was 1. Oncogenic HPV subtypes were detected in 4% of oral, 26% of penile, and 74% of vaginal samples, including HPV16 in 1, 12, and 21% of these samples respectively. Genital HPV prevalence was significantly higher than oral HPV prevalence (75 vs. 15%, p ≤ 0.001). Thirty-five percent of couples (12/34) had at least one type-specific concordant vaginal-penile HPV infection but only one of nine couples with oral HPV had concordant oral–oral infection. However, 67% (4/6) of men and 25% (1/4) of women with oral HPV infection had partners with concordant genital HPV infection.
Implications and Impact: Oral–oral HPV concordance between couples is low, but oral-genital and genital–genital HPV concordance is higher, including concordance of male oral HPV infection with their partners’ vaginal HPV infection. This data is consistent with possible transmission of vaginal HPV infection to the oral cavity of sexual partners performing oral sex.
HIV; oral sex; South Africa; HPV; oral; genital; concordance; transmission
Male circumcision (MC) reduces penile high-risk human papillomavirus (HR-HPV) on the coronal sulcus and urethra. HR-HPV varies by anatomic site, and it is unknown whether MC decreases HR-HPV on the penile shaft. We assessed the efficacy of MC to reduce HR-HPV on the penile shaft and compared it to known efficacy of MC to reduce HR-HPV on the coronal sulcus. HIV-negative men randomized to receive immediate circumcision (intervention) or circumcision delayed for 24 months (control) were evaluated for HR-HPV at 12 months post-enrollment using the Roche HPV Linear Array assay. Among swabs with detectable beta-globin or HPV, year 1 HR-HPV prevalence on the coronal sulcus was 21.5% in the intervention arm and 36.3% in the control arm men (adjusted prevalence risk ratios (PRR)=0.57, 95%CI 0.39–0.84, p=0.005). On the shaft, year 1 HR-HPV prevalence was 15.5% in the intervention and 23.8% in the control arm (adjusted PRR=0.66, 95%CI 0.39–1.12, p=0.12). Efficacy of MC to reduce HR-HPV on the shaft was similar to efficacy on the coronal sulcus (p=0.52). In a sensitivity analysis in which swabs without detectable beta-globin or HPV were included as HPV negative, prevalence of HR-HPV on the shaft was lower in the intervention arm (7.8%) than control arm (13.6%) (PRR 0.57, 95%CI 0.33–0.99, p<0.05). HR-HPV was more frequently detected on the coronal sulcus than penile shaft among uncircumcised men (36.3% vs 23.8%, respectively, p=0.02) and circumcised men (21.5% vs 15.5%, respectively, p=0.24). MC reduced HR-HPV prevalence on both the coronal sulcus and shaft.
Male circumcision; human papillomavirus (HPV); HIV; Uganda; foreskin; penis; coronal sulcus; penile shaft; cervical cancer; sexually transmitted infections
Background. Women diagnosed with cervical cancer report longer duration and more recent use of combined oral contraceptives (COCs). It is unclear how COC use impacts risk of cervical carcinogenesis.
Methods. We estimated the risk of new human papillomavirus (HPV) DNA detection and persistence among 1135 human immunodeficiency virus (HIV)–negative women aged 20–37 years from Thailand who were followed for 18 months at 6-month intervals. Type-specific HPV DNA, demographic information, hormonal contraceptive use, sexual behavior, genital tract coinfection, and Papanicolaou test results were assessed at baseline and each follow-up.
Results. Women who reported current COC use during follow-up were less likely to clear HPV infection compared with nonusers, independent of sexual behavior, and Papanicolaou test diagnosis (AHR: 0.67 [95% CI: .49–.93]). Similar associations were not observed among women reporting current use of depomedroxyprogesterone acetate (DMPA). Neither COC nor DMPA use was significantly associated with new HPV DNA detection.
Conclusions. These data do not support the hypothesis that contraceptive use is associated with cervical cancer risk via increased risk of HPV acquisition. The increased risk of HPV persistence observed among current COC users suggests a possible influence of female sex hormones on host response to HPV infection.
Carcinogenic human papillomavirus (HPV) infections are necessary causes of most anogenital cancers. Viral load has been proposed as a marker for progression to cancer precursors but has been confirmed only for HPV16. Challenges in studying viral load are related to the lack of validated assays for a large number of genotypes. We compared viral load measured by Linear Array (LA) HPV genotyping with the gold standard, quantitative PCR (Q-PCR). LA genotyping and Q-PCR were performed in 143 cytology specimens from women referred to colposcopy. LA signal strength was measured by densitometry. Correlation coefficients and receiver operating characteristic (ROC) analyses were used to evaluate analytical and clinical performance. We observed a moderate to strong correlation between the two quantitative viral load measurements, ranging from an R value of 0.61 for HPV31 to an R value of 0.86 for HPV52. We also observed agreement between visual LA signal strength evaluation and Q-PCR. Both quantifications agreed on the disease stages with highest viral load, which varied by type (cervical intraepithelial neoplasia grade 2 [CIN2] for HPV52, CIN3 for HPV16 and HPV33, and cancer for HPV18 and HPV31). The area under the curve (AUC) for HPV16 Q-PCR at the CIN3 cutoff was 0.72 (P = 0.004), and the AUC for HPV18 LA at the CIN2 cutoff was 0.78 (P = 0.04). Quantification of LA signals correlates with the current gold standard for viral load, Q-PCR. Analyses of viral load need to address multiple infections and type attribution to evaluate whether viral load has clinical value beyond the established HPV16 finding. Our findings support conducting comprehensive studies of viral load and cervical cancer precursors using quantitative LA genotyping data.
High-risk human papillomavirus (HR-HPV) testing is increasingly important. We therefore examined the impact on accuracy of repeated versus one-time testing, type-specific versus pooled detection, and assay analytic sensitivity. By using a nested case-control design from the ASCUS-LSIL Triage Study, we selected women with incident cervical intraepithelial neoplasia grade 2 or grade 3 (CIN2/3; n = 325) and a random sample of women with
We compared the performance of commonly used Dacron versus flocked nylon swabs for anal cytology.
From 23 HIV-positive men screened at Kaiser Permanente San Francisco (San Francisco, Calif., USA), 2 anal specimens were collected, 1 with each swab in random order, and placed into liquid cytology medium. Specimens were tested for cellularity by quantifying a genomic DNA (erv-3). The number of cells was assessed from prepared slides by automated image analysis. Performance was compared between swabs using 2-sample t tests and standard crossover trial analysis methods accounting for period effect.
Flocked swabs collected slightly more erv-3 cells than Dacron for the first sample although not significantly (p = 0.18) and a similar number of erv-3 cells for the second sample (p = 0.85). Flocked swabs collected slightly more cells per slide than the Dacron swabs at both time periods although this was only significant in the second time period (p = 0.42 and 0.03 for first and second periods, respectively). In crossover trial analysis, flocked swabs outperformed Dacron for cell count per slide based on slide imaging (p = 0.03), but Dacron and flocked swabs performed similarly based on erv-3 quantification (p = 0.14).
Further studies should determine whether flocked swabs increase the representation of diagnostically important cells compared to Dacron.
Cytology; Anal neoplasia; Human papillomavirus testing; Screening; Cytological techniques
To increase participation in cervical cancer screening of under-served women living in the Mississippi Delta, a U.S. population at high risk for cervical cancer
We conducted a door-to-door feasibility study of women living in the Mississippi Delta to increase participation in cervical cancer screening in 2009-10. Women (n=119) aged 26-65 years who had not been screened in last 3 years or more, were not pregnant, and had a cervix were offered a choice: clinic-based Pap testing or home self-collection with HPV DNA testing.
Seventy-seven women (64.7%) chose self-collection with HPV testing, of which 62 (80.5%) returned their self-collected specimen. By comparison, 42 women (35.3%) chose Pap testing, of which 17 (40.5%) attended their clinic appointment. Thus there was an almost 4-fold greater participation of under-screened women in self-collection with HPV testing than in free Pap testing (78.4% vs. 21.5%).
We found that offering self-collection will increase participation in cervical cancer screening among under-screened populations living in the Mississippi Delta. Based on these preliminary results, we suggest that self-collection with HPV DNA testing might complement current Pap testing programs to reach under-screened populations of women, such as those living in the Mississippi Delta.
Pap; cervical intraepithelial neoplasia (CIN); cervical cancer; human papillomavirus (HPV); atypical squamous cells of undetermined significance (ASC-US); Hybrid Capture 2 (HC2); health disparities; cervical cancer screening
To explore alternative cervical cancer screening approaches in an underserved population, we compared the performance of human papillomavirus (HPV) DNA assays in combination with different sample collection methods for primary cervical screening in the Mississippi Delta region. Three specimens were collected from women aged 26 to 65 years who were either routinely undergoing screening (n = 252) or not (n = 191): clinician-collected cervical specimens, clinician-collected cervicovaginal specimens, and self-collected cervicovaginal specimens taken at home. A novel collection device and medium were used for cervicovaginal sampling. Specimens were tested by three HPV DNA assays: hybrid capture 2 (HC2; Qiagen Corp., Gaithersburg, MD), Linear Array (LA; Roche Molecular Systems, Pleasanton, CA), and Amplicor (Roche Molecular Systems, Pleasanton, CA). Liquid-based cytology was performed on cervical specimens. We compared the overall positivity (a proxy for clinical specificity) for any carcinogenic HPV genotype and calculated the agreement across assay and specimen type using McNemar's test for differences in test positivity. Across all three assays there were no significant differences between clinician-collected and self-collected cervicovaginal specimens (P > 0.01 for all comparisons). For both cervicovaginal specimens (clinician collected and self-collected), fewer women tested positive by HC2 than by LA or Amplicor (P < 0.01 for all comparisons). HC2 had the best agreement between specimens for all assays. HC2 is likely more clinically specific, although possibly less sensitive, than either PCR test. Thus, use of HC2 on cervicovaginal specimens for screening could result in fewer referrals compared to LA and Amplicor.
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