Prevalence and risk factors of HPV infection among high-risk rural and urban Lithuanian women

AIMS: To investigate the prevalence, persistence and risk factors of high oncogenic risk human papillomavirus (HPV) among urban and rural women of reproductive age coming to consult a gynaecologist. METHODS: A prospective cohort study in urban (Kaunas) and rural (Marijampole) regions of Lithuania. The data were collected in 8 healthcare institutions from women seeking consultation of gynaecologists using a questionnaire for finding out demographic, social, behavioural and biomedical factors. HPV DNA was determined by molecular hybridization method (hybrid capture version II) determining HPV of high oncogenic risk. RESULT: 1,120 women participated in the study. The prevalence of high-risk HPV among the studied women was 25.1%. It was higher among the urban women than among the rural women. The prevalence of high-risk HPV was increased if the subjects had 2 or more sexual partners during the last 12 months (OR 2.81; 95% CI 1.83-4.32), were 19 years of age or younger (OR 2.68; 95% CI 1.47-4.91), were smoking (OR 1.81; 95% CI 1.16-2.81), and had secondary or lower education level (OR 1.43; 95% CI 1.01-2.04). This infection was obviously associated with high- and low-grade squamous intraepithelial changes of the cervix (OR 1.66, 95% CI = 1.08-2.53). CONCLUSION: The incidence rate for cervical cancer in Lithuania is one of the highest in comparison with other European countries. HPV infection was also particularly common in the studied population. About one-fourth of the women were infected with high-risk HPV infection. Young and less educated women were found to be the group that was most exposed to HPV, and therefore public health interventions and education seem to be essential in programs aimed at reducing the incidence of cervical cancer.     

Prevalence and predictors of squamous intraepithelial lesions of the cervix in HIV-infected women in Lusaka, Zambia

OBJECTIVES: HIV-infected women living in resource-constrained nations like Zambia are now accessing antiretroviral therapy and thus may live long enough for HPV-induced cervical cancer to manifest and progress. We evaluated the prevalence and predictors of cervical squamous intraepithelial lesions (SIL) among HIV-infected women in Zambia. METHODS: We screened 150 consecutive, non-pregnant HIV-infected women accessing HIV/AIDS care services in Lusaka, Zambia. We collected cervical specimens for cytological analysis by liquid-based monolayer cytology (ThinPrep Pap Test) and HPV typing using the Roche Linear Array PCR assay. RESULTS: The median age of study participants was 36 years (range 23-49 years) and their median CD4+ count was 165/microL (range 7-942). The prevalence of SIL on cytology was 76% (114/150), of which 23.3% (35/150) women had low-grade SIL, 32.6% (49/150) had high-grade SIL, and 20% (30/150) had lesions suspicious for squamous cell carcinoma (SCC). High-risk HPV types were present in 85.3% (128/150) women. On univariate analyses, age of the participant, CD4+ cell count, and presence of any high-risk HPV type were significantly associated with the presence of severely abnormal cytological lesions (i.e., high-grade SIL and lesions suspicious for SCC). Multivariable logistic regression modeling suggested the presence of any high-risk HPV type as an independent predictor of severely abnormal cytology (adjusted OR: 12.4, 95% CI 2.62-58.1, p=0.02). CONCLUSIONS: The high prevalence of abnormal squamous cytology in our study is one of the highest reported in any population worldwide. Screening of HIV-infected women in resource-constrained settings like Zambia should be implemented to prevent development of HPV-induced SCC.     

Prevalence of bacterial vaginosis: 2001-2004 National Health and Nutrition Examination Survey data

OBJECTIVE: To estimate the prevalence and correlates of bacterial vaginosis among women between the ages of 14 and 49 years in the United States. METHODS: Data from the 2001-2001 and 2003-2004 National Health and Nutrition Examination Surveys were combined. Correlates of bacterial vaginosis evaluated included sociodemographic characteristics (age, race or ethnicity, education, poverty income ratio) and sexual history (age of first intercourse, number of sexual partners). Crude and adjusted odds ratios and 95% confidence intervals were estimated from logistic regression analyses. RESULTS: Almost one third of women (29%) were positive for bacterial vaginosis. Bacterial vaginosis prevalence varied with age, race or ethnicity, education, and poverty. Black, non-Hispanic (odds ratio [OR] 3.13, 95% confidence interval [CI] 2.58-3.80) and Mexican-American (OR 1.29, 95% CI 0.99-1.69) women had higher odds of bacterial vaginosis than white, non-Hispanic women after adjustment for other sociodemographic characteristics. Douching in the past 6 months was also an important predictor of bacterial vaginosis prevalence (OR 1.93, 95% CI 1.54-2.40). CONCLUSION: Bacterial vaginosis is a common condition among U.S. women, and the prevalence is similar to that in many treatment-seeking populations. Further studies are needed to disentangle the interactions between race or ethnicity and other sociodemographic characteristics. LEVEL OF EVIDENCE: III.     

Risk factors for human papillomavirus and cervical precancerous lesions, and the role of concurrent HIV-1 infection.

OBJECTIVES: To identify risk factors for human papillomavirus (HPV) infection and squamous intraepithelial lesions (SIL) of the cervix, and to measure the impact of concurrent HIV-1 infection. METHODS: Women were studied at a family planning clinic in Nairobi, Kenya. Demographic and historical information was obtained using a semi-structured questionnaire and specimens were collected for sexually transmitted diseases (STDs), HPV, cervical cytology, and HIV-1 testing. RESULTS: HPV was detected in 87 of 513 women (17%), including 81 (93%) oncogenic types (16, 18, 31, 33 and others) and six (7%) non-oncogenic types (6 and 11). HIV-1 prevalence was 10%. HPV detection was associated with HIV-1 infection [adjusted odds ratio (aOR) 3.9, 95% confidence interval (CI), 2.0-7.7], sexual behavior indicators including the number of sex partners and inflammatory STDs, as well as the number of pregnancies (0 or 1 vs. > or = 3, aOR 0.4; 95% CI, 0.2-0.9). SIL was detected in 61 women (11.9%), including 28 (46%) with low-grade lesions (LSIL) and 33 (54%) with high-grade lesions (HSIL). HPV infection was strongly associated with HSIL (OR 14.9; 95% CI, 6.8-32.8). In a multivariate model predictors of HSIL included HIV-1 serpositivity (aOR 4.8; 95% CI, 1.8-12.4), the number of lifetime sex partners (0-1 vs. > or = 4; aOR 3.8; 95% CI, 1.1-13.5), and older age (< 26 vs. > 30; OR 3.9; 95% CI, 1.1-13.6). An analysis stratified by HIV-1 showed a stronger association between HPV and HSIL in HIV-1 negative women (OR 17.0; 95% CI, 6.4-46.3) then in HIV-1 positive women (OR 4.5; 95% CI, 0.8-27.4). CONCLUSION: Our results indicate that HSIL and even invasive cancer are highly prevalent in this setting of women on reproductive age considered to be at low risk for STDs, suggesting that routine Pap smear screening may save lives.     

The role of high-risk HPV-DNA testing in the male sexual partners of women with HPV-induced lesions

OBJECTIVES: The objectives were to assess the prevalence of high-risk HPV in the male sexual partners of women with HPV-induced lesions, and correlate it with biopsies guided by peniscopy. STUDY DESIGN: Fifty-four asymptomatic male sexual partners of women with low-grade squamous intra-epithelial lesions (LSIL) associated with high-risk HPV were examined between April 2003 and June 2005. The DNA-HPV was tested using a second-generation hybrid capture technique in scraped penile samples. Peniscopy identified acetowhite lesions leading to biopsy. RESULTS: High-risk HPV was present in 25.9% (14 out of 54) of the cases. Peniscopy led to 13 biopsies (24.07%), which resulted in two cases of condyloma, two cases of intra-epithelial neoplasia (PIN) I, one case of PIN II, and eight cases of normal tissue. The high-risk HPV test demonstrated 80% sensitivity, 100% specificity, 100% positive predictive value, and 88.9% negative predictive value for the identification of penile lesions. There was a greater chance of finding HPV lesions in the biopsy in the positive cases of high-risk HPV with abnormal peniscopy (p=0.007); OR=51 (CI 1.7-1527.1). CONCLUSION: Among asymptomatic male sexual partners of women with low-grade intra-epithelial squamous lesions, those infected by high-risk HPV have a higher chance of having abnormal penile tissue compared with male partners without that infection.     

Human papillomavirus DNA detection and histological findings in women referred for atypical glandular cells or adenocarcinoma in situ in their Pap smears

OBJECTIVE: To evaluate the association between high-risk human papillomavirus (HPV) DNA detection and histological diagnosis in women referred for atypical glandular cells (AGC) or adenocarcinoma in situ (AIS) at Pap smear. METHODS: In this cross-sectional study, 146 women referred for AGC (124), AGC with high-grade squamous intraepithelial lesion (HSIL) (15), or AIS (7) were tested for HPV DNA using Hybrid Capture II (HC II). All women underwent colposcopic examination, and cervical biopsy was performed for 95 patients. Fifty-one women referred due to AGC with normal colposcopy and normal second Pap smear were scheduled for control visits every 4 months. RESULTS: The overall prevalence of HPV DNA was 38%. HPV DNA was detected in 93% of the women with HSIL associated with AGC and in 71% of women with AIS Pap smear, being significantly higher when compared with the prevalence (29%) in women with AGC alone. Forty-five women (30.8%) had clinically significant histological lesions (CIN 2 or worse). High-risk HPV DNA was detected in only 16% of the women without significant abnormalities in biopsy, in contrast to 96% of those who had CIN 2 or CIN 3 and 75% of women with AIS. Eighty-five percent of women with invasive cervical carcinoma (squamous or adenocarcinoma) tested positive for HPV DNA. HPV DNA detection was significantly associated with histological diagnosis of CIN 2 or worse, with an odds ratio (OR) = 51.8 (95% CI 14.3-199.9). CONCLUSION: HPV DNA detection was strongly associated with the severity of cervical lesion (CIN 2 or worse) in women referred for AGC or AIS in their Pap smear. These data implicate the use of HPV testing in triage of women with AGC Pap smears.     

Genetic polymorphisms of GSTM1, p21, p53 and HPV infection with cervical cancer in Korean women

OBJECTIVES: The aim of this study was to determine whether GSTM1 or GSTT1 might be associated with risk of cervical cancer development in Korean women. The multiplicative interaction of GSTM1 and GSTT1 genotype with p21, p53 polymorphism, and HPV genotype was also investigated. METHODS: From 1997 to 1999, uterine cervical carcinoma was diagnosed in 215 Korean women at the Department of Obstetrics and Gynecology of Seoul National University Hospital. None of the women in the control groups (n = 98) had any evidence of cervical lesions, which were confirmed by Pap smear. Finally, 81 cases and 86 controls were genotyped for p21, p53, and GSTM1 and T1 and HPV infection. A multiplex PCR method was used for the genotyping of GSTM1 and GSTT1; direct sequencing for p53 codon 72, high-risk HPV, and PCR-RFLP (BsmAI) for p21 codon. The unconditional logistic regression analysis was used to calculate ORs and 95% CI. RESULTS: Although the GSTM1 and GSTT1 genotype was not significantly associated with cervical cancer development for all women, the GSTM1 null genotype was significantly associated with an increased risk of cervical cancer development in women with high-risk HPV infection (OR = 2.9, 95% CI: 1.0-8.2). Although the frequency of overall GSTT1 null genotype was significantly lower in cervical carcinoma patients with high-risk HPV infection (OR = 0.3, 95% CI: 0.1-1.0), almost 2-fold increased risk was observed among women with GSTT1 null and Arg/Arg genotype (OR = 1.9, 95% CI: 0.7-5.4). Although the cervical cancer risk was 3.3-fold increased in women with null and Arg/Arg genotype compared to women with GSTM1 present and p21 Ser-containing genotype, there was no significant multiplicative interaction between GSTM1 and p21 (P for interaction = 0.785) or p53 (P for interaction = 0.815). CONCLUSIONS: These findings suggest that the risk of cervical cancer may be related to GSTM1 genotype in women with high-risk HPV infection and that there is a possible gene-gene interaction in the incidence of cervical cancer.     

Atypical squamous cells of undetermined significance: human papillomavirus testing in adolescents

OBJECTIVE: To estimate the age-stratified prevalence of oncogenic human papillomavirus (HPV) infection and to evaluate risk factors for HPV acquisition among women with atypical squamous cells of undetermined significance (ASC-US). METHODS: This was a chart review of all women with ASC-US smears who underwent oncogenic HPV testing between July 2002 and February 2004. To be eligible, HPV DNA results had to be available. Data extracted from charts included demographic information as well as certain patient characteristics historically associated with HPV acquisition or carriage. RESULTS: Of 527 eligible women with ASC-US, 357 (68%, 95% confidence interval [CI] 64-72%) tested positive for oncogenic HPV. As compared with women who tested negative, this population was significantly younger and less likely to be married. When stratified by age, 77% of the women aged younger than 20 years were positive for high-risk subtypes, compared with 58% of women aged older than 25 years (P < .01). In the multivariate analysis, young age (relative risk [RR] 1.30, 95% CI 1.14.-1.49), current smoking (RR 1.14, 95% CI 1.03-1.25) and a history of chlamydial infection (RR 1.20, 95% CI 1.09-1.32) were associated with an increased likelihood of HPV infection, while oral contraceptive use (RR 0.86, 95% CI 0.72-1.03) had a marginal protective effect. The protective effect of oral contraceptives was most pronounced among adolescent women (RR 0.57, 95% CI 0.31-1.03). CONCLUSION: Given that the rate of oncogenic HPV infection approached 80% in our population of adolescent women with ASC-US, the usefulness of HPV testing in this age group requires further investigation. LEVEL OF EVIDENCE: II-3.     

Association between genital mycoplasmas infection and human papillomavirus infection,abnormal cervical cytopathology,and cervical cancer: a systematic review and meta-analysis

Background

Some studies demonstrated that female genital mycoplasmas play important roles in human papillomavirus (HPV) infection, abnormal cervical cytopathology, and cervical cancer. However, those results remained inconclusive. We aimed to perform a systematic review and meta-analysis to investigate the association between female genital mycoplasmas and those disorders.

Methods

Computerized databases were comprehensively searched before 26 January 2017. Pooled odd radios (ORs) and correlative 95% confidence intervals (CIs) were adopted to evaluate the strength of association.

Results

Our meta-analysis included 22 studies with 16,181 participants. Ureaplasma urealyticum and Ureaplasma parvum were associated with a significantly increased risk of overall HPV infection (OR 1.57, 95% CI 1.05–2.34; OR 3.02, 95% CI 2.10–4.33, respectively), and U. urealyticum and Mycoplasma genitalium were associated with a significantly increased risk of high-risk HPV infection (OR 1.37, 95% CI 1.05–1.80; OR 1.50, 95% CI 1.11–2.02, respectively). In addition, U. urealyticum, U. parvum, and Mycoplasma hominis were associated with a significantly increased risk of abnormal cervical cytopathology (OR 1.51, 95% CI 1.23–1.85; OR 1.41, 95% CI 1.10–1.80; OR 1.48, 95% CI 1.10–1.99, respectively).

Conclusion

We found that U. urealyticum and M. genitalium may increase the risk of high-risk HPV infection, while U. urealyticum, U. parvum, and M. hominis may increase the risk of abnormal cervical cytopathology.

     

Psychological and biological markers of stress and bacterial vaginosis in pregnant women

OBJECTIVES: To determine whether stress is associated with risk of bacterial vaginosis (BV) in pregnant women. DESIGN: Prospective cohort study. SETTING: The prenatal care clinics at the University of North Carolina. The residents' clinic sees mostly government-insured and uninsured women, and the physicians' clinic sees mostly those with private health insurance. POPULATION: A total of 897 women gave samples for BV analysis. Study participants were 22% African-American, 68% white; 24% unmarried and 44% nulliparous. More than half had completed college. METHODS: Women completed two questionnaires and two interviews reporting stress and psychological aspects of their lives. Measurement scales included the Sarason life events questionnaire, the Cohen perceived stress scale, Spielberger state-trait anxiety, the John Henryism coping style and the Medical Outcomes Study social support inventory. Two stress hormones, corticotrophin-releasing hormone and cortisol, were also measured. MAIN OUTCOME MEASURES: BV at 15-19 and 24-29 weeks of gestation was diagnosed by Gram's stain. RESULTS: Women in the highest quartile of stress measures, particularly state anxiety (OR=2.0, 95% CI 1.2-3.3), perceived stress (OR=2.4, 95% CI 1.5-3.9) and total life events (OR=2.0, 95% CI 1.3-3.2), had the highest risk of BV. Adjustment for confounders, especially age, race, and income, reduced these associations (state anxiety: OR=1.3, 95% CI 0.7-2.4; perceived stress: OR=1.4, 95% CI 0.8-2.5; total life events: OR=1.3, 95% CI 0.7-2.4). No clear pattern of association was seen between stress hormones and BV. CONCLUSIONS: Few associations between stress and BV were seen after adjustment for confounders.     

Increased risk of cervical disease among human immunodeficiency virus-infected women with severe immunosuppression and high human papillomavirus load(1)

OBJECTIVE: To investigate human papillomavirus (HPV) genotypes, HPV DNA load, and behavioral and sociodemographic factors in a series of human immunodeficiency virus (HIV)-seropositive women, and to correlate HPV infection with cervical disease according to immune status. METHODS: Three hundred seven HIV-seropositive women were tested for the presence of HPV DNA by polymerase chain reaction (PCR) and Southern blot hybridization. Cervical disease was assessed using Papanicolaou smears, colposcopy, and biopsies when necessary. Various risk factors for cervical intraepithelial neoplasia (CIN) were tested using multiple logistic regression analysis. RESULTS: Cervical disease was diagnosed in 83 (27.0%) of 307 women and HPV infection in 162 (52.8%). High HPV load (as detectable by Southern blot hybridization) was found in 90 (55.6%) of the 162 infected women. Potentially oncogenic or related genotypes were detected in 74 (82.2%) of these 90 cases. High-load HPV infection was twice as frequent in severely immunosuppressed women (CD4 cell count less than 200/microL) as in women with higher CD4 cell counts (P =.002). High-load HPV infection was associated with a high risk of cervical disease (adjusted odds ratio [OR] 16.8; 95% confidence interval [CI] 7.0, 40.3). The risk among severely immunosuppressed women was ten times greater than that among women with CD4 cell counts of at least 200/microL. Low-load HPV infection (detected by PCR only) was a risk factor for CIN in severely immunosuppressed women only (adjusted OR 7.4; 95% CI 1.3, 43.0). CONCLUSION: Immunosuppression favors cervical high-load HPV infection with oncogenic genotypes and its clinical expression in HIV-seropositive women.     

Human papillomavirus testing as an optional screening tool in low-resource settings of Latin America: experience from the Latin American Screening study

Hybrid capture II (HC II) test for oncogenic human papillomaviruses (HPV) was carried out in a cohort of 4284 women at their first clinical visit. Overall prevalence of HPV was 17.1%, decreasing with age from 33.9% among women below 20 years to only 11.0% among those older than 41 years. HPV prevalence was significantly higher among current smokers (odds ratio [OR] = 1.31; 95% CI 1.1-1.6), in women with two or more lifetime sexual partners (OR = 1.9; 95% CI 1.6-2.4), and those women with two or more sexual partners during the past 12 months prior to examination (OR = 1.6; 95% CI 1.2-2.2). HPV detection increased in parallel with increasing cytologic abnormality, being highest in women with high-grade squamous intraepithelial lesion (P= 0.001). Specificity of the HPV test in detecting histologically confirmed cervical disease was 85% (95% CI 83.9-86.1). Sensitivity of the HPV test in detecting histologic abnormalities increased in parallel with disease severity, ranging from 51.5% for cervical intraepithelial neoplasia (CIN) 1 to 96.5% for CIN 3 and 100.0% for cancer, with respective decline of positive predictive value. These data suggest that HPV testing with HC II assay might be a viable screening tool among this population with relatively high prevalence of cervical disease.     

A multicenter study of bacterial vaginosis in women with or at risk for human immunodeficiency virus infection

BACKGROUND: Bacterial vaginosis is a common gynecologic infection that has been associated with a variety of gynecologic and obstetric complications, including pelvic inflammatory disease, postabortal infection and premature delivery. Recent studies suggest that bacterial vaginosis may increase a woman's risk for human immunodeficiency virus (HIV). We undertook this study to assess whether the prevalence and characteristics of bacterial vaginosis differed according to HIV status in high-risk US women. METHODS: Prevalence of bacterial vaginosis was assessed by Gram's stain and clinical criteria for 854 HIV-infected and 434 HIV-uninfected women enrolled in the HIV Epidemiology Research (HER) Study. Multiple logistic regression techniques were used to determine whether HIV infection independently predicted bacterial vaginosis. RESULTS: Almost half (46%) the women had bacterial vaginosis by Gram's stain. The prevalence of bacterial vaginosis was 47% in the HIV-positive women compared with 44% in the HIV-negative women; this difference was not statistically significant (p = 0.36). After adjustment for other covariates, HIV-positive women were more likely than HIV-negative women to have bacterial vaginosis (odds ratio (OR) 1.31; 95% confidence interval (CI) 1.01-1.70) by Gram's stain but not by clinical criteria (OR 1.16; CI 0.87-1.55). Among HIV-positive women, use of antiretroviral drugs was associated with a lower prevalence of bacterial vaginosis (adjusted OR 0.54; Cl 0.38-0.77). CONCLUSIONS: In this cross-sectional analysis of high-risk US women, HIV infection was positively correlated with bacterial vaginosis diagnosed by Gram's stain.     

A population-based study of cervical carcinoma and HPV infection in Latvia

OBJECTIVES: We wished to quantify the population-based importance of cervical carcinoma risk factors in Latvia. METHODS: Totally, 223 of 224 eligible cases of incident invasive cervical carcinoma were enrolled during July 1998-February 2001 in Latvia. An age-matched sample of 300 healthy control women was selected from the Latvian population registry and 239 of these women (79%) were enrolled. A demographic and life-style questionnaire was completed, cervical brush samples were analyzed for human papillomavirus (HPV) DNA by PCR and serum samples for HPV antibodies. RESULTS: Risk factors for cervical cancer in multivariate analysis were HPV type 16 or 18 DNA positivity (OR = 32.4; CI 95% 16.5-63.6) and living in the capital (OR = 2.4; CI 95% 1.2-4.7). Oral contraceptive use was not a risk factor (OR = 0.4; CI 95% 0.2-1.1). A strong protective effect was found for having had more than three Pap smears in the last 5 years (OR = 0.07 CI 95% 0.03-0.19). CONCLUSIONS: Inadequate population coverage of Pap smears, in spite of excessive smear usage, caused 28.4% of cervical cancers in age groups eligible for screening. HPV type 16 infection was the most important risk factor for cervical cancer in Latvia, with a population-attributable risk percent for all ages of 58.5%.     

Human papillomavirus genotyping using HPV DNA chip analysis in Korean women

This study was designed to investigate the genotypes of human papillomavirus (HPV) in Korean women who had abnormal cervical cytology and to evaluate the clinical accuracy of HPV DNA chip analysis for the diagnosis of cervical neoplasia. Liquid-based cytology preparations, HPV DNA chip analysis, and cervical biopsy were performed in 2358 women. High-risk HPV was identified in 23.5% of 1650 histologically confirmed normal samples (including cervicitis and squamous metaplasia) and in 81.8% of 708 samples with cervical intraepithelial neoplasia (CIN) and carcinoma (P<0.01). The major prevalent high-risk HPV genotypes in 381 samples of CIN II/III were HPV-16, -58, -33, and -31, in order of prevalence rate (average overall, 78.0%), and HPV-16, -18, -58, and -33 (average overall, 81.2%) in 133 samples of squamous cell carcinoma (SCC). The infection rate of HPV-16 was significantly higher than that of other high-risk HPV genotypes in all normal, CIN, and SCC cases (P < 0.01) and increased with more advanced squamous cervical lesions (P<0.01). The detection accuracy of high-risk HPV using HPV DNA chip analysis for CIN II or worse was as follows: sensitivity 84% (81-87%), specificity 72% (70-74%), positive predictive value 47% (44-50%), and negative predictive value 94% (92-95%). These results suggest that HPV DNA chip analysis may be a reliable diagnostic tool for the detection of cervical neoplasia and that there are geographic differences in the distribution of high-risk HPV genotypes.     

Human papillomavirus infection and female infertility: a systematic review and meta-analysis

There is increasing evidence that human papillomavirus (HPV) infection affects reproductive health and fertility, although its impact on female fertility has not been thoroughly studied. MEDLINE, Embase, CENTRAL, Web of Science, CNKI, Wanfang, VIP and ClinicalTrials.gov databases were systematically searched for relevant articles. A meta-analysis was conducted of 11 studies including 15,450 female subjects that compared HPV prevalence between the infertile and general population, and evaluated the association between HPV positivity and female infertility. Seven case–control studies on 3581 participants reported indiscriminate genotype infections (high-risk/low-risk [HR/LR]-HPV), but the random effects model revealed no association between HPV infection and female infertility (odds ratio [OR] 2.13, 95% confidence interval [CI] 0.97–4.65, P = 0.06). Six studies with a total of 11,869 participants reported HR-HPV infections alone, and the pooled data showed a significant association between HR-HPV infection and female infertility (OR 2.33, 95% CI 1.42–3.83, P = 0.0008). It was concluded that HR-HPV infection is a potential risk factor of female infertility, but not an independent cause. Further prospective studies are needed to assess the exact role of HPV in female infertility.     

Estonian medical birth registry 1992–1994: Association of risk factors with perinatal mortality

Objective: To investigate the association of different maternal sociodemographic characteristics and infant sex with perinatal mortality among primiparas and multiparas. Study design: Analysis of routine data from the Estonian Medical Birth Registry covering the whole of Estonia. A total of 47 358 infants (including stillborns) with a birth weight 1000 g or more from 1992 through 1994 were studied. Perinatal mortality rate, crude odds ratio (OR) and adjusted OR (calculated by a logistic regression model) were used to evaluate the association. OR values were adjusted for maternal age at delivery, maternal ethnicity, educational level, residence, marital status, smoking status, history of previous abortion and infant sex. Results: The perinatal mortality rate was 12.2 per 1000 total births among primiparous and 14.3 among multiparous women. The highest adjusted ORs of perinatal deaths were found in older (35 years and over) primiparas (1.78; 95% confidence interval (CI 0.88-3.57)) and multiparas (1.81; 95% CI 1.29-2.55), in unmarried (single) primiparas (1.59; 95% CI 1.14-2.20) and multiparas (1.98; 95% CI 1.29-3.05), in smoking primiparas (1.69; 95% CI 1.09-2.63) and multiparas (1.51; 95% CI 1.02-2.25), and in multiparas with unknown smoking status (1.98; 95% CI 1.18-3.33). Conclusion: The study provides further evidence that perinatal mortality is positively associated with increased maternal age, unmarried (single) status and smoking.     

The distribution and differential risks of human papillomavirus genotypes in cervical preinvasive lesions: a Taiwan Cooperative Oncologic Group Study

To clarify the distribution and relative risk of different human papillomavirus (HPV) genotypes in cervical preinvasive lesions, 1246 women with abnormal Papanicolaou smear including atypical squamous cell of unknown significance (ASCUS), atypical glandular cell of unknown significance (AGUS), low-grade squamous intraepithelial lesion (LSIL), and high-grade squamous intraepithelial lesion (HSIL) were enrolled in a multicenter, cross-sectional study. Colposcopy and HPV tests with hybrid capture 2 and polymerase chain reaction-reverse line blot were performed. The prevalences of HPV in ASCUS/AGUS-negative histology, ASCUS/AGUS, LSIL, HSIL, and invasive cancer were 33.8%, 38.3%, 74.9%, 84.3% and 100%, respectively, with an overall positive rate of 68.8%. The most common HPV types were HPV 16 (18.5%), 52 (16.5%), 58 (13.2%), 33, 51, 53, 18, 39, 59, 66, MM8, and 31. In comparing the relative risk of HPV infection in different disease status, LSIL and HSIL/carcinoma had a 4.64 (95% CI: 2.98-7.24) and 10.53 (95% CI: 6.69-16.58) folds of risk of high-risk HPV infection than the negative group. The same was true in mixed HPV infection, but not in low-risk type infection. Looking into each high-risk HPV type, the relative infection risks for LSIL and HSIL/carcinoma, in comparison with the negative group, were 1.67 (0.63-4.43) and 8.67 (3.46-21.70), 2017 (1.01-4.68) and 3.04 (1.42-6.47), and 1.40 (0.52-3.77) and 5.22 (2.07-13.19) for HPV type 16, 52 and 58, respectively. The study confirmed the high prevalence and risky nature of HPV 52 and 58 in Taiwanese population and conveyed the need to include these HPV types in vaccine development.     

Primary high-risk HPV screening for cervical cancer in post-menopausal women

Objective

The present study was conducted to examine the value of screening for high-risk HPV in post-menopausal women.

Methods

A cohort of post-menopausal women (n = 2113), age range 55-76 years, from Uppsala County, Sweden, were offered testing for both high-risk HPV and a Pap smear in the gynaecological screening during 2008-2010. For the HPV test the cervical smear sample was applied to a filter paper matrix, an indicating FTA elute card and HPV typing performed using a real-time PCR assay. Histological verified CIN2+ lesion was used as an end-point measurement.

Results

High-risk HPV were found in 6.2% (95% CI 5.2-7.3%) of the women (n = 130) and 22% (95% CI 14-32%) (n = 17) of these had CIN2+ lesions based on histology. The Pap smear taken in conjunction with the HPV test was abnormal in 9.7% (95% CI 5.7-16.3%) (n = 12) of HPV positive women. Among HPV positive women with an abnormal Pap smear, the frequency of histology verified CIN2+ lesions was 67% (95% CI 38-86%) (n = 8), as compared to 14% (95% CI 7-24%) (n = 9) in HPV positive women with a normal smear. The prevalence of HPV16 in CIN2+ lesions (29%, 95% CI 22-37%) in post-menopausal women was less than half of previous estimates in pre-menopausal women from this population.

Conclusions

Most histological CIN2+ lesions in post-menopausal women are not recognized by a single Pap smear. A large fraction of pre-invasive cervical cancer cases in post-menopausal women result from infections by HPV types not included in the present vaccine formulas.