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Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) are prevalent in sub-Saharan Africa, together with HIV; the consequent burden of disease is grave. The cofactors driving transmission of the two viruses and pathogenesis of associated malignancies are not well understood. We measured KSHV and EBV DNA in whole blood and saliva as well as serum antibodies levels in 175 Cameroonians with Kaposi's sarcoma and 1,002 age- and sex-matched controls with and without HIV. KSHV seroprevalence was very high (81%) in controls, while EBV seroprevalence was 100% overall. KSHV DNA was detectable in the blood of 36-46% of cases and 6-12% of controls; EBV DNA was detected in most participants (72-89%). In saliva, more cases (50-58%) than controls (25-28%) shed KSHV, regardless of HIV infection. EBV shedding was common (75-100%); more HIV+ than HIV- controls shed EBV. Cases had higher KSHV and EBV VL in blood and saliva then controls, only among HIV+ participants. KSHV and EBV VL were also higher in HIV+ than in HIV- controls. Cases (but not controls) were more likely to have detectable KSHV in blood if they also had EBV, whereas shedding of each virus in saliva was independent. While EBV VL in saliva and blood were modestly correlated, no correlation existed for KSHV. Numerous factors, several related to parasitic coinfections, were associated with detection of either virus or with VL. These findings may help better understand the interplay between the two gammaherpesviruses and generally among copathogens contributing to cancer burden in sub-Saharan Africa.

The role of host epigenetic mechanisms in the natural history of low-grade cervical intraepithelial neoplasia (CIN1) is not well characterized. We explored differential methylation of imprinted gene regulatory regions as predictors of the risk of CIN1 regression. A total of 164 patients with CIN1 were recruited from 10 Duke University clinics for the CIN Cohort Study. Participants had colposcopies at enrollment and up to five follow-up visits over 3 years. DNA was extracted from exfoliated cervical cells for methylation quantitation at CpG (cytosine-phosphate-guanine) sites and human papillomavirus (HPV) genotyping. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression to quantify the effect of methylation on CIN1 regression over two consecutive visits, compared to non-regression (persistent CIN1; progression to CIN2+; or CIN1 regression at a single time-point), adjusting for age, race, high-risk HPV (hrHPV), parity, oral contraceptive and smoking status. Median participant age was 26.6 years (range: 21.0-64.4 years), 39% were African-American, and 11% were current smokers. Most participants were hrHPV-positive at enrollment (80.5%). Over one-third of cases regressed (n = 53, 35.1%). Median time-to-regression was 12.6 months (range: 4.5-24.0 months). Probability of CIN1 regression was negatively correlated with methylation at IGF2AS CpG 5 (HR = 0.41; 95% CI = 0.23-0.77) and PEG10 DMR (HR = 0.80; 95% CI = 0.65-0.98). Altered methylation of imprinted IGF2AS and PEG10 DMRs may play a role in the natural history of CIN1. If confirmed in larger studies, further research on imprinted gene DMR methylation is warranted to determine its efficacy as a biomarker for cervical cancer screening.

A systematic review of the literature was conducted to determine the estimates of and definitions for human papillomavirus (HPV) persistence in women following treatment of cervical intra-epithelial neoplasia (CIN). A total of 45 studies presented data on post-treatment HPV persistence among 6,106 women. Most studies assessed HPV persistence after loop excision (42%), followed by conization (7%), cryotherapy (11%), laser treatment (4%), interferon-alpha, therapeutic vaccination, and photodynamic therapy (2% each) and mixed treatment (38%). Baseline HPV testing was conducted before or at treatment for most studies (96%). Follow-up HPV testing ranged from 1.5 to 80 months after baseline. Median HPV persistence tended to decrease with increasing follow-up time, declining from 27% at 3 months after treatment to 21% at 6 months, 15% at 12 months, and 10% at 24 months. Post-treatment HPV persistence estimates varied widely and were influenced by patient age, HPV-type, detection method, treatment method, and minimum HPV post-treatment testing interval. Loop excision and conization appeared to outperform cryotherapy procedures in terms of their ability to clear HPV infection. This systematic review provides evidence for the substantial heterogeneity in post-treatment HPV DNA testing practices and persistence estimates.

As China's population ages, the importance of determining prevalence of cervical disease and accurate cervical cancer screening strategies for postmenopausal women is increasing.17 population-based studies were analyzed to determine prevalence of cervical neoplasia in postmenopausal women. All women underwent HPV DNA testing, visual inspection with acetic acid (VIA), and cytology testing. Diagnostic values for primary and combinations screening methods included sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), referral rate, and area under curve (AUC) were calculated using directed biopsy or 4 quadrants biopsy as reference standard. Premenopausal and postmenopausal women had equal HPV infection and cervical neoplasia rates (p-value >0.05). HPV DNA testing CIN3+ sensitivity, specificity, PPV, NPV, referral rate, and AUC were 97.9% (95%CI: 90.2-99.9%), 84.2% (95%CI: 82.8-85.5%), 9.9% (95%CI: 7.4-12.8%), 100% (95%CI: 99.8-100%), 17.2% (95%CI: 15.9-18.7%), 0.911, respectively. VIA values were 41.7% (95%CI: 28.4-55.9%), 94.5% (95% CI: 93.6-95.3%), 11.8% (95%CI: 7.5-17.3%), 98.9% (95%CI: 98.5-99.3%), 6.2% (95%CI: 5.3-7.1%), and 0.681, respectively. Values for VIA and HPV triage were 39.6% (95% CI: 26.6-53.8%), 99.2% (95%CI: 98.8-99.5%), 45.2% (95%CI: 30.8-60.4%), 98.9% (95%CI: 98.5-99.3%), 1.5% (95%CI: 1.1-2.0%), and 0.694, respectively. VIA and HPV DNA co-test values were 100% (95% CI: 94.0-100%), 79.5% (95%CI: 78.0-81.0%), 8.0% (95% CI: 6.0-10.3%), 100% (95%CI: 99.9-100%), 21.9% (95%CI: 20.4-23.4%), and 0.898, respectively. VIA sensitivity decreases significantly in postmenopausal women compared to premenopausal performance. HPV DNA testing maintained performance between pre- and postmenopausal women and is the most accurate primary modality for screening postmenopausal populations in low resource areas of China. This article is protected by copyright. All rights reserved.

A systematic review of the literature was conducted to determine the estimates of and definitions for human papillomavirus (HPV) persistence in women following treatment of cervical intra-epithelial neoplasia (CIN). A total of 45 studies presented data on post-treatment HPV persistence among 6,106 women. Most studies assessed HPV persistence after loop excision (42%), followed by conization (7%), cryotherapy (11%), laser treatment (4%), interferon-alpha, therapeutic vaccination, and photodynamic therapy (2% each) and mixed treatment (38%). Baseline HPV testing was conducted before or at treatment for most studies (96%). Follow-up HPV testing ranged from 1.5 to 80 months after baseline. Median HPV persistence tended to decrease with increasing follow-up time, declining from 27% at 3 months after treatment to 21% at 6 months, 15% at 12 months, and 10% at 24 months. Post-treatment HPV persistence estimates varied widely and were influenced by patient age, HPV-type, detection method, treatment method, and minimum HPV post-treatment testing interval. Loop excision and conization appeared to outperform cryotherapy procedures in terms of their ability to clear HPV infection. This systematic review provides evidence for the substantial heterogeneity in post-treatment HPV DNA testing practices and persistence estimates.

As China's population ages, the importance of determining prevalence of cervical disease and accurate cervical cancer screening strategies for postmenopausal women is increasing. Seventeen population-based studies were analyzed to determine prevalence of cervical neoplasia in postmenopausal women. All women underwent HPV DNA testing, visual inspection with acetic acid (VIA) and cytology testing. Diagnostic values for primary and combinations screening methods included sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), referral rate and area under curve (AUC) were calculated using directed biopsy or four quadrants biopsy as reference standard. Premenopausal and postmenopausal women had equal HPV infection and cervical neoplasia rates (p 0.05). HPV DNA testing CIN3+ sensitivity, specificity, PPV, NPV, referral rate and AUC were 97.9% (95% CI: 90.2-99.9%), 84.2% (95% CI: 82.8-85.5%), 9.9% (95% CI: 7.4-12.8%), 100% (95% CI: 99.8-100%), 17.2% (95% CI: 15.9-18.7%), 0.911, respectively. VIA values were 41.7% (95% CI: 28.4-55.9%), 94.5% (95% CI: 93.6-95.3%), 11.8% (95% CI: 7.5-17.3%), 98.9% (95% CI: 98.5-99.3%), 6.2% (95% CI: 5.3-7.1%) and 0.681, respectively. Values for VIA with HPV triage were 39.6% (95% CI: 26.6-53.8%), 99.2% (95% CI: 98.8-99.5%), 45.2% (95% CI: 30.8-60.4%), 98.9% (95% CI: 98.5-99.3%), 1.5% (95% CI: 1.1-2.0%) and 0.694, respectively. VIA and HPV DNA co-test values were 100% (95% CI: 94.0-100%), 79.5% (95% CI: 78.0-81.0%), 8.0% (95% CI: 6.0-10.3%), 100% (95% CI: 99.9-100%), 21.9% (95% CI: 20.4-23.4%) and 0.898, respectively. VIA sensitivity decreases significantly in postmenopausal women compared to premenopausal performance. HPV DNA testing maintains performance between pre- and postmenopausal women and is the most accurate primary modality for screening postmenopausal populations in low resource areas of China.

Persistent high-risk human papillomavirus (HR-HPV) infection is the strongest risk factor for high-grade cervical precancer. We performed a systematic review and meta-analysis of HPV persistence patterns worldwide. Medline and ISI Web of Science were searched through January 1, 2010 for articles estimating HPV persistence or duration of detection. Descriptive and meta-regression techniques were used to summarize variability and the influence of study definitions and characteristics on duration and persistence of cervical HPV infections in women. Among 86 studies providing data on over 100,000 women, 73% defined persistence as HPV positivity at a minimum of two time points. Persistence varied notably across studies and was largely mediated by study region and HPV type, with HPV-16, 31, 33 and 52 being most persistent. Weighted median duration of any-HPV detection was 9.8 months. HR-HPV (9.3 months) persisted longer than low-risk HPV (8.4 months), and HPV-16 (12.4 months) persisted longer than HPV-18 (9.8 months). Among populations of HPV-positive women with normal cytology, the median duration of any-HPV detection was 11.5 and HR-HPV detection was 10.9 months. In conclusion, we estimated that approximately half of HPV infections persist past 6 to 12 months. Repeat HPV testing at 12-month intervals could identify women at increased risk of high-grade cervical precancer due to persistent HPV infections.

To optimize HPV vaccination implementation at the population-level in China, data are needed on age-specific HPV 16, 18, 6 and 11 prevalence. This cross-sectional, population-based study evaluated the age- and type-specific HPV 16, 18, 6 and 11 prevalence of DNA and serum antibodies among women in China. From July 2006 to April 2007, 17 to 54-year-old women from three rural provinces (Xinjiang, Shanxi, and Henan) and two cities (Beijing and Shanghai) provided cervical exfoliated cells for HPV DNA and liquid-based cervical cytology (SurePath). High and low-risk HPV types were detected with HC-II (Qiagen), with genotyping of HPV-positive samples using Linear Array (Roche). HPV 16, 18, 6, and 11 serum antibodies were detected using a Luminex-based, competitive immunoassay (Merck and Co). A total of 4,206 women with DNA and serum antibody results were included. HPV 16 DNA prevalence peaked in women aged 30–34 (4.2%) and 45–49 years (3.8%), while HPV 18 DNA prevalence peaked at ages 40–44 years (1.3%). Most women were dually DNA and serum antibody negative: HPV 16 (92.2%), 18 (97.2%), HPV 16 & 18 (90.2%), 6 (92.0%), 11 (96.6%), 6 & 11(89.9%), and HPV 16, 18, 6, & 11 (82.5%). Future national HPV vaccination programs in China should target younger women due to increased exposure to HPV types 16, 18, 6 and 11 with age. Cumulative exposure of HPV may be underreported in this population as cross-sectional data do not accurately reflect exposure to HPV infections over time.

The APTIMA HPV Assay (AHPV) allows detection of 14 high-risk human papillomavirus (HPV) RNA types in cervical specimens. Until present, the assay has been compared to HPV DNA tests only in triage settings. Herein, we compare AHPV with a DNA assay (Hybrid Capture 2; HC2) and liquid-based cytology (LBC; using PreservCyt ThinPrep liquid Pap) in a screening setting (French APTIMA screening evaluation [FASE] study). Women (N = 5,006) aged 20-65 were screened by gynecologists in 17 private practices in Paris, France. One cervical specimen was collected and tested with LBC, AHPV and HC2 assays. Women were referred to colposcopy if they were ASC-US+ in LBC or HPV positive in either HPV assay. To control for verification bias, a random group (14%) with normal LBC and dually HPV negative tests underwent colposcopy. Data from 4,429 women were analyzed. Sensitivity, specificity and predictive values were calculated for the three tests. AHPV and HC2 were highly sensitive for CIN2+ (92.0% and 96.7%) and CIN3+ (95.7% and 95.3%) detection and much more sensitive than LBC (69.1% for CIN2+ and 73.3% for CIN3+). Specificity of AHPV was higher than that of HC2, but similar to that of LBC (p < 0.001). Combining LBC with either HPV test slightly increased sensitivity but compromised specificity. AHPV assay is both specific and sensitive for the detection of high-grade precancerous lesions and may be considered as an option for routine cervical cancer screening for women over 20 years of age.

Human papillomavirus (HPV) prevalence was estimated from 2,705 sexually active, uncircumcised, human immunodeficiency virus seronegative men aged 17-28 years in Kisumu, Kenya. HPV prevalence was 51.1% (95% confidence interval: 49.2-53.0%) in penile cells from the glans/coronal sulcus and/or shaft. HPV prevalence varied by anatomical site, with 46.5% positivity in the glans/coronal sulcus compared with 19.1% in the shaft (p < 0.0001). High-risk HPV was detected in 31.2% of glans and 12.3% of shaft samples (p < 0.0001). HPV16 was the most common type and 29.2% of men were infected with more than one HPV type. Risk factors for HPV infection included presence of C. trachomatis, N. gonorrhea, self-reported sexually transmitted infections, and less frequent bathing. Lifetime number of sexual partners and herpes simplex virus type-2 seropositivity were also marginally associated with HPV infection.

To determine whether Chlamydia trachomatis infection is consistently associated with an increased risk of invasive cervical carcinoma (ICC) after accounting for the strong effect of human papillomavirus (HPV) infection, a case-control study of 1,238 cases of ICC and 1,100 control women from 7 countries was carried out (hospital-based studies in Thailand, the Philippines, Morocco, Peru, Brazil and population-based studies in Colombia and Spain, all coordinated by the International Agency for Research on Cancer, Lyon, France). C. trachomatis serum antibody detection was made by means of a microfluorescence assay. Among HPV DNA-positive cases and controls, the risk of squamous cell ICC was elevated in C. trachomatis seropositive women (OR = 1.8; 95% CI = 1.2-2.7) after adjustment for age, center, oral contraceptive use, history of Pap smears, number of full-term pregnancies and herpes simplex virus 2 seropositivity. The effect of C. trachomatis seropositivity on squamous cell ICC risk increased with increasing C. trachomatis antibody titers and was higher in women under 55 years of age. C. trachomatis antibodies were not associated with adeno- or adenosquamous cell carcinoma (OR = 1.0; 95% CI = 0.53-1.9) in HPV DNA-positive women. An association of C. trachomatis with squamous cell ICC was found among all cases and control women with or without adjustment for HPV.

The incidence rate of invasive cervical carcinoma (ICC) is 4-fold higher in Ho Chi Minh City, in the South of Vietnam, than in Hanoi, in the North. Thus, we explored the prevalence of and the risk factors for human papillomavirus (HPV) infection in these 2 areas. A population-based random sample of married women aged 15-69 years were interviewed and had a gynaecological examination in the urban district of Ho Chi Minh City and in a peri-urban district in Hanoi. HPV DNA detection was performed using a GP5+/6+ primer-mediated PCR enzyme immunoassay. A total of 922 women from Ho Chi Minh and 994 from Hanoi, for whom a Pap smear and HPV-status were available, were evaluated. HPV DNA was detected among 10.9% of women in Ho Chi Minh City and 2.0% in Hanoi (age standardized prevalence, world standard population: 10.6% and 2.3%, respectively). In the 2 areas combined, 30 different HPV types were found, the most common being HPV 16 (in 14 single and 18 multiple infections), followed by HPV 58, 18 and 56. A peak of HPV DNA detection in women younger than age 25 was found in Ho Chi Minh City (22.3%) but not in Hanoi. Major risk factors for HPV DNA detection were indicators of sexual habits, most notably the presence of HSV-2 antibodies, nulliparity and the current use of oral contraceptives. Women in Hanoi showed the lowest HPV prevalence ever reported so far, suggesting that HPV has not spread widely in this population. As expected, HPV prevalence in a population seemed to be closely correlated with ICC incidence rates.

To investigate the prevalence of and the risk factors for human papillomavirus (HPV) infection in South Korea, we interviewed and examined a randomly selected sample of 863 sexually active women (age range = 20–74 years, median 44) and 103 self-reported virgins from Busan. The presence of DNA of 34 different HPV types in cervical exfoliated cells was tested among sexually active women by means of a PCR-based assay. IgG antibodies against L1 virus-like particles (anti-VLPs) of HPV types 16, 18, 31, 33 and 58 were also evaluated by means of ELISA. The overall prevalence of HPV DNA was 10.4% (95% confidence interval, CI: 8.5–12.7%). The most often found HPV DNA types were HPV 70, HPV 16 and HPV 33; 19.8% (95% CI: 17.2–22.0) of sexually active women had antibodies against one or more HPV types. The most common anti-VLPs were against HPV 18, 31 and 16. Prevalences standardized by age on the basis of the world standard population were 13.0% for HPV DNA and 17.1% for anti-VLPs. The concordance between the 2 HPV markers at an individual level was modest, but the risk factors for detection of HPV DNA and anti-VLPs were similar: number of lifetime sexual partners (odds ratio, OR for ≥ 4 vs. 1 = 3.5 and 5.4, respectively), seropositivity for herpes simplex virus-2 antibodies (OR = 2.6 and 2.5, respectively) and being single or divorced. HPV DNA, but not anti-VLPs, were elevated among women whose husbands were thought by their wives to have extra-marital affairs and those who had undergone vasectomy. Among 103 virgins, 4.9% had anti-VLPs (1/73 among those aged 24 years or less). © 2002 Wiley-Liss, Inc.

HPV types 16 and 18 have been categorized as human carcinogens based on their strong associations with cervical cancer in previous case-control studies. Recent IARC studies in the Philippines, Thailand and Morocco show strong associations between invasive cervical cancer and less common HPV types, including HPV 31, 33, 45, 51, 52 and 58. We present results of a further IARC case-control study conducted in Asuncion, Paraguay, to examine the association between specific HPV types and invasive cervical cancer as well as risk factors other than HPV. One-hundred thirteen incident histologically confirmed invasive cervical cancer cases and 91 age-matched hospital controls were recruited. A standardized questionnaire was administered to investigate known and suspected risk factors for cervical cancer. For HPV status determination, cervical biopsy specimens from case subjects and exfoliated cervical cells from control subjects were obtained. HPV DNA was ascertained using a GP5+/6+ PCR-based assay capable of detecting more than 33 HPV types. Overall HPV prevalence was 97% in the cervical cancer cases and 20% in the control subjects. As a single infection, HPV 16 was the predominant type with a prevalence of 48% among case subjects and 5.5% among control subjects. Significant associations with the risk of cervical cancer were detected as follows: any HPV type (OR = 114; 95% CI: 36-361); HPV 16 (OR = 910); HPV 18 (infinite OR); HPV 31 (OR = 110); HPV 33 (OR = 261); HPV 45 (OR = 129); and HPV 58 (OR = 36). In the multivariate model, risk factors other than HPV significantly associated with cervical cancer risk were a higher number of lifetime sexual partners, lower educational status and never having had a Pap smear. Strong associations were found between invasive cervical cancer and specific HPV types 16, 18, 31, 33, 45 and 58.

To determine why a vaginal self-collection tested for high-risk human papillomavirus (HR-HPV) by Hybrid Capture 2(R) (hc2) has lower sensitivity and specificity for cervical intraepithelial neoplasia Grade 2 or worse (or = CIN 2), we collected 5 specimens (endocervix, upper and lower vagina, perineum, vaginal self-collection) from 2,625 women. Endocervical and self-collected specimens had HR-HPV tests by hc2. All 5 anogenital specimens were tested for 37 HPV genotypes [Linear Array(R), (LA)] from 397 women hc2 positive in endocervical or self-collected specimens and for a randomly selected 71 of 2,228 women hc2 negative on both specimens. Three hundred nintey-five women who screened positive by hc2 or had abnormal cytology underwent colposcopic evaluation. Of 47 women withor = CIN 2, hc2 was positive in 97.9% (46/47) of endocervical and 80.9% (38/47), p = 0.008 of self-collected specimens. Seven of 9 women withor = CIN 2 and negative self-collected hc2 tests were positive for HR-HPV by LA. Of 2,578 women withoutor = CIN 2, hc2 was positive in 9.8% (253/2,578) of endocervical and 11.4% (294/2,578), p = 0.001 of self-collected specimens. Of the 41 more women withoutor = CIN 2 that tested hc2 positive on the self-collected but negative on endocervical specimen, LA tested positive for HR-HPV in 24, negative for HPV in 11 and negative for HR-HPV but positive for low-risk HPV in 6. Lower sensitivity of self-collected specimens is secondary to lower levels of vaginal HR-HPV. The principal cause of the lower specificity of self-collected specimens is HR-HPV present solely in the vagina, which is not associated withor = CIN 2.

A systematic review was conducted of HPV type distribution in anal cancer and anal high-grade and low-grade squamous intraepithelial lesions (HSIL and LSIL). A Medline search of studies using PCR or hybrid capture for HPV DNA detection was completed. A total of 1,824 cases were included: 992 invasive anal cancers, 472 HSIL cases and 360 LSIL cases. Crude HPV prevalence in anal cancer, HSIL, and LSIL was 71, 91 and 88%, respectively. HPV16/18 prevalence was 72% in invasive anal cancer, 69% in HSIL and 27% in LSIL. The HPV 16 and/or 18 prevalence in invasive anal cancer cases was similar to that reported in invasive cervical cancer. If ongoing clinical trials show efficacy in preventing anal HPV infection and associated anal lesions, prophylactic HPV vaccines may play an important role for the primary prevention of these cancers in both genders.

As acetic acid-aided visual inspection (VIA) and colposcopic-directed biopsy miss small ≥cervical intraepithelial neoplasia (CIN) 2, inflation of sensitivity of VIA may occur when colposcopic-directed biopsy is the gold standard for ≥CIN 2. To determine whether such inflation occurs, we reviewed 375 women with ≥CIN 2 from the Shanxi Province Cervical Cancer Screening Study II. These women had positive self or physician-collected tests for high-risk human papillomavirus or abnormal cervical cytology and had VIA followed by colposcopy with directed biopsy and endocervical curettage (ECC). If a cervical quadrant had no lesion, a random biopsy at the squamocolumnar junction within that quadrant was obtained. Sensitivity of colposcopic-directed biopsy was higher for ≥CIN 2 involving 3–4 cervical quadrants (81.3%) than for ≥CIN 2 involving 0–2 quadrants (49.0%, p < 0.001). Sensitivities of VIA, cytology of ≥ASC-US, ≥LSIL, and ≥HSIL were higher for ≥CIN 2 involving 3–4 quadrants than for ≥CIN 2 involving 0–2 quadrants. When a colposcopic-directed biopsy gold standard was compared with that of a 5-biopsy standard (which included ≥CIN 2 from colposcopic-directed biopsy, random biopsy, or ECC), the sensitivity for ≥CIN 2 of VIA was inflated by 20.0% (65.9% vs. 45.9%, p < 0.001). Sensitivities of other screening tests were not affected. Similar inflation of sensitivity of VIA was found with an endpoint of ≥CIN 3 (70.4% vs. 52.0%, p = 0.0013). Inflation of sensitivity of VIA depended upon agreement between colposcopic-directed biopsy and the screening tests as measured by kappa. Studies of VIA that used colposcopic-directed biopsy as the gold standard require reevaluation. © 2007 Wiley-Liss, Inc.

Data on human papillomavirus (HPV) type distribution in invasive and pre-invasive cervical cancer is essential to predict the future impact of HPV16/18 vaccines and HPV-based screening tests. A meta-analyses of HPV type distribution in invasive cervical cancer (ICC) and high-grade squamous intraepithelial lesions (HSIL) identified a total of 14,595 and 7,094 cases, respectively. In ICC, HPV16 was the most common, and HPV18 the second most common, type in all continents. Combined HPV16/18 prevalence among ICC cases was slightly higher in Europe, North America and Australia (74-77%) than in Africa, Asia and South/Central America (65-70%). The next most common HPV types were the same in each continent, namely HPV31, 33, 35, 45, 52 and 58, although their relative importance differed somewhat by region. HPV18 was significantly more prevalent in adeno/adenosquamous carcinoma than in squamous cell carcinoma, with the reverse being true for HPV16, 31, 33, 52 and 58. Among HSIL cases, HPV16/18 prevalence was 52%. However, HPV 16, 18 and 45 were significantly under-represented, and other high-risk HPV types significantly over-represented in HSIL compared to ICC, suggesting differences in type-specific risks for progression. Data on HPV-typed ICC and HSIL cases were particularly scarce from large regions of Africa and Central Asia.

Persistent infection with high-risk human papillomavirus (HPV) is central to cervical carcinogenesis. Certain high-risk types, such as HPV16, may be more persistent than other HPV types, and type-specific HPV persistence may differ by HIV serostatus. This study evaluated the association between HPV type and clearance of HPV infections in 522 HIV-seropositive and 279 HIV-seronegative participants in the HIV Epidemiology Research Study (HERS, United States, 1993-2000). Type-specific HPV infections were detected using MY09/MY11/HMB01-based PCR and 26 HPV type-specific probes. The estimated duration of type-specific infections was measured from the first HPV-positive visit to the first of two consecutive negative visits. Hazard ratios (HRs) and 95% confidence intervals (CIs) for HPV clearance were calculated using Cox models adjusted for study site and risk behavior (sexual or injection drugs). A total of 1,800 HPV infections were detected in 801 women with 4.4 years median follow-up. HRs for clearance of HPV16 and related types versus low-risk HPV types were 0.79 (95% CI: 0.64-0.97) in HIV-positive women and 0.86 (95% CI: 0.59-1.27) in HIV-negative women. HRs for HPV18 versus low-risk types were 0.80 (95% CI: 0.56-1.16) and 0.57 (95% CI: 0.22-1.45) for HIV-positive and -negative women, respectively. HPV types within the high-risk category had low estimated clearance rates relative to low-risk types, but HRs were not substantially modified by HIV serostatus.

To determine whether Chlamydia trachomatis infection is consistently associated with an increased risk of invasive cervical carcinoma (ICC) after accounting for the strong effect of human papillomavirus (HPV) infection, a case-control study of 1,238 cases of ICC and 1,100 control women from 7 countries was carried out (hospital-based studies in Thailand, the Philippines, Morocco, Peru, Brazil and population-based studies in Colombia and Spain, all coordinated by the International Agency for Research on Cancer, Lyon, France). C. trachomatis serum antibody detection was made by means of a microfluorescence assay. Among HPV DNA-positive cases and controls, the risk of squamous cell ICC was elevated in C. trachomatis seropositive women (OR = 1.8; 95% CI = 1.2-2.7) after adjustment for age, center, oral contraceptive use, history of Pap smears, number of full-term pregnancies and herpes simplex virus 2 seropositivity. The effect of C. trachomatis seropositivity on squamous cell ICC risk increased with increasing C. trachomatis antibody titers and was higher in women under 55 years of age. C. trachomatis antibodies were not associated with adeno- or adenosquamous cell carcinoma (OR = 1.0; 95% CI = 0.53-1.9) in HPV DNA-positive women. An association of C. trachomatis with squamous cell ICC was found among all cases and control women with or without adjustment for HPV.

The incidence rate of invasive cervical carcinoma (ICC) is 4-fold higher in Ho Chi Minh City, in the South of Vietnam, than in Hanoi, in the North. Thus, we explored the prevalence of and the risk factors for human papillomavirus (HPV) infection in these 2 areas. A population-based random sample of married women aged 15-69 years were interviewed and had a gynaecological examination in the urban district of Ho Chi Minh City and in a peri-urban district in Hanoi. HPV DNA detection was performed using a GP5+/6+ primer-mediated PCR enzyme immunoassay. A total of 922 women from Ho Chi Minh and 994 from Hanoi, for whom a Pap smear and HPV-status were available, were evaluated. HPV DNA was detected among 10.9% of women in Ho Chi Minh City and 2.0% in Hanoi (age standardized prevalence, world standard population: 10.6% and 2.3%, respectively). In the 2 areas combined, 30 different HPV types were found, the most common being HPV 16 (in 14 single and 18 multiple infections), followed by HPV 58, 18 and 56. A peak of HPV DNA detection in women younger than age 25 was found in Ho Chi Minh City (22.3%) but not in Hanoi. Major risk factors for HPV DNA detection were indicators of sexual habits, most notably the presence of HSV-2 antibodies, nulliparity and the current use of oral contraceptives. Women in Hanoi showed the lowest HPV prevalence ever reported so far, suggesting that HPV has not spread widely in this population. As expected, HPV prevalence in a population seemed to be closely correlated with ICC incidence rates.

To investigate the prevalence of and the risk factors for human papillomavirus (HPV) infection in South Korea, we interviewed and examined a randomly selected sample of 863 sexually active women (age range = 20-74 years, median 44) and 103 self-reported virgins from Busan. The presence of DNA of 34 different HPV types in cervical exfoliated cells was tested among sexually active women by means of a PCR-based assay. IgG antibodies against L1 virus-like particles (anti-VLPs) of HPV types 16, 18, 31, 33 and 58 were also evaluated by means of ELISA. The overall prevalence of HPV DNA was 10.4% (95% confidence interval, CI: 8.5-12.7%). The most often found HPV DNA types were HPV 70, HPV 16 and HPV 33; 19.8% (95% CI: 17.2-22.0) of sexually active women had antibodies against one or more HPV types. The most common anti-VLPs were against HPV 18, 31 and 16. Prevalences standardized by age on the basis of the world standard population were 13.0% for HPV DNA and 17.1% for anti-VLPs. The concordance between the 2 HPV markers at an individual level was modest, but the risk factors for detection of HPV DNA and anti-VLPs were similar: number of lifetime sexual partners (odds ratio, OR for/= 4 vs. 1 = 3.5 and 5.4, respectively), seropositivity for herpes simplex virus-2 antibodies (OR = 2.6 and 2.5, respectively) and being single or divorced. HPV DNA, but not anti-VLPs, were elevated among women whose husbands were thought by their wives to have extra-marital affairs and those who had undergone vasectomy. Among 103 virgins, 4.9% had anti-VLPs (1/73 among those aged 24 years or less).

Extensive experimental and limited epidemiologic data suggest that adeno-associated viruses (AAV) can have antioncogenic activity and may be protective factors for the development of cervical cancer. To examine the association between AAV-2 IgG antibodies and cervical neoplasia in Spain and Colombia, we tested for AAV-2 antibodies using an ELISA assay for 109 women with invasive cervical cancer, 100 population-based controls age-matched to the invasive cases, 77 women with carcinoma in situ (CIN III) and 100 clinic-based controls age-matched to the CIN III cases. Human papillomavirus (HPV) DNA was detected in cervical exfoliated cells by polymerase chain reaction using HPV-L1 and GP5+/6+ consensus primers. The prevalence of AAV-2 antibody titers >100 was significantly lower in invasive cervical cancer cases than control participants. When comparing women with invasive cancer with controls or with CIN III cases, a pattern of decreasing cervical cancer risk with increasing AAV-2 titers was observed. Elevated AAV antibody titers (>100) were inversely associated with invasive cervical cancer (OR 0.3; 95% CI 0.1–0.7), although results were not statistically significant after controlling for HPV (OR 0.4; 95% CI 0.1–1.6). In contrast, AAV-2 antibodies were not significantly associated with the risk of CIN III (OR 1.4; 95% CI 0.3–6.8). These results provide supportive evidence that AAV infection may be a protective factor for the development of invasive cervical cancer. Alternatively, the lower AAV-2 seroprevalence in invasive cervical cancer cases may be due to an immunosuppressive effect of cervical cancer on AAV antibody response. To investigate whether a direct viral interaction is occurring, future studies should aim to resolve at what frequency AAV is found in the genital tract and to clarify further whether AAV may infect the same HPV-positive cells in the cervix. © 2001 Wiley-Liss, Inc.