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.     

Human papillomavirus testing improves the accuracy of colposcopy in detection of cervical intraepithelial neoplasia

To assess the performance of human papillomavirus (HPV) testing and colposcopy in detection of cervical pathology. A series of 389 women referred for colposcopy due to an abnormal Pap smear had cervical swabs analyzed for oncogenic (high-risk [HR]) HPV types using Hybrid Capture II (HC2) assay. Loop electrical excision procedure cone biopsy (88%) or colposcopic biopsy (11%) was used as the gold standard. Of the atypical squamous cells of undetermined significance (ASCUS) smears, 48% were positive for HR HPV, as compared to 76.3% of low-grade squamous intraepithelial lesions (LSIL) smears. HR HPV was detected in 66.7% and 90% of patients with cervical intraepithelial neoplasia (CIN) 1 and CIN2 (or higher), respectively. The sensitivity of the Pap smear using an ASCUS threshold in detecting high-grade CIN was 94.5% (95% confidence intervals (CI): 91-97%) and that of colposcopy 98.5% (95% CI: 95-99%). The respective specificities were 30% (95% CI: 17-28%) and 35.6% (CI: 29-42%). HC2 test had comparable sensitivity, 90% (95% CI: 85-93%), but higher specificity, 54.3% (95% CI: 47-61%). Combining HC2 test with Pap increased specificity, 66.7% and 41.3% for ASCUS and LSIL cutoff, respectively. The minor-abnormality threshold together with HC2 increased specificity of colposcopy with no changes in sensitivity. High viral load (>100 relative light unit/positive control) was associated with significant disease. HPV DNA testing improves the accuracy of colposcopy in the detection of high-grade CIN in women with ASCUS or LSIL smears.     

A comparison of the human papillomavirus test and Papanicolaou smear as a second screening method for women with minor cytological abnormalities

BACKGROUND: Of the estimated one million Papanicolaou (pap) smears performed annually in Sweden, about 4% show any degree of abnormality. Approximately, 1% of these cases contain moderate or severe atypia (high-grade squamous intraepithelial lesions) and the rest contain low-grade atypia. Recommendations for the management of minor abnormalities vary in various parts of Sweden. Generally, a second Pap smear is obtained 4-6 months after the first one showing low-grade atypia. The aim of this study is to compare the sensitivity of human papilloma virus (HPV)-DNA testing for the detection of cervical intraepithelial neoplasia (CIN) 2-3 with that of a second Pap smear in women, who had low-grade atypia in their first Pap smear. METHODS: Women with low-grade atypia in the Stockholm area, detected at a population-based cytology screening, were enrolled. A repeat Pap smear, HPV test, and colposcopically directed biopsies were obtained. For the detection of HPV, Hybrid Capture II (HC II) was used. RESULTS: The HPV-DNA test was positive in 66% of the 177 participating women. The sensitivity of the second Pap smear and HPV-DNA test to detect CIN 2-3 was 61 (95% CI = 45-74) and 82% (95% CI = 67-91), respectively. The positive and negative predictive values of HPV testing were 27 (95% CI = 18-35) and 89% (95% CI = 80-97), respectively. CONCLUSIONS: In Sweden, a second Pap smear is often obtained for the follow-up of women with low-grade atypia. The results of our study show that compared to the second Pap smear, HPV testing with HC II is a more sensitive method for detecting high-grade lesions.     

Demographic, risk factor, and knowledge differences between Latinas and non-Latinas referred to colposcopy

OBJECTIVE: Disparities occur in the incidence and mortality of cervical cancer among minority women in the US. Screening lowers cervical cancer incidence. Screening rates are lower for minority women than for White women in the US. This study sought to identify demographic, risk factor, and perception of the role of Pap smears between Latinas and non-Latinas. METHODS: A written survey was administered to 150 Latinas and 150 non-Latinas attending a colposcopy unit. Data on demographics, risk factors, screening rates, knowledge about cervical cancer screening, and perceived barriers to participation in screening programs were collected. RESULTS: A total of 140 Latinas and 146 non-Latinas completed the survey. Marital status and health insurance status were similar in the two groups. 30% of Latinas and 73.3% of non-Latinas reported completing college (p<0.0001). Only 55.7% of Latinas were employed, compared to 82.2% of non-Latinas (p<0.0001). 21% of Latinas and 53.4% of non-Latinas reported an annual income greater than 35,000 dollars (p<0.0001). Among Latinas, women with 1-5 lifetime Pap smears were less likely to have completed college than those with more than 5 lifetime Pap smears (OR=2.11; 95% CI 1.05-4.22) and to have an annual income of less than 35,000 dollars (OR=3.81; 95% CI 1.64-8.87). Latinas were less likely to have > or =6 lifetime sexual partners, use tobacco, and have a history of sexually transmitted infections. Latinas more commonly reported fear of test results (OR, 0.04; 95% CI 0.02-0.09) and inability to communicate with their provider in Spanish (p<0.0001) as barriers to screening than the non-Latina respondents. CONCLUSIONS: Several of the barriers limiting access to cervical cancer screening programs are also present among screened Latinas undergoing further evaluation for abnormal Pap smears.     

CYP1A1, GSTM1, and GSTT1 polymorphisms and the risk of cervical squamous intraepithelial lesions in a multiethnic population

OBJECTIVE: In this investigation, we explored the hypothesis that genetic polymorphisms in the cytochrome P4501A1 (T3801C) and glutathione S-transferase classes mu and theta (GSTM1 and GSTT1) gene deletions promote the development of cervical dysplasia by moderating the activation and detoxification of polycyclic hydrocarbons and other compounds that influence oxidative stress and DNA adduct formation. METHODS: A multiethnic, case-control study of 131 women with biopsy-confirmed cervical squamous intraepithelial lesions (SIL) and 180 controls with cytologically normal cervical (Pap) smears was conducted between 1992 and 1996 in Honolulu, Hawaii. We collected in-person interviews, a blood sample to extract genomic DNA, and an exfoliated cervical cell sample to determine the presence and type of human papillomavirus (HPV) using PCR dot-blot hybridization. Genotyping for the CYP1A1 MspI allelic variant and deletion of the GSTM1 and GSTT1 gene loci followed a PCR method. RESULTS: Women who were homozygous, but not heterozygous, for the CYP1A1 MspI variant allele were at significantly increased risk of cervical SIL (odds ratio (OR) = 3.4; 95% confidence interval (CI) = 1.1-10.7) compared to women who were homozygous for the wild-type allele. Subjects with the GSTM1 null genotype had a nonsignificant elevated risk of cervical SIL (OR = 1.6; 95% CI = 0.8-3.0) compared to women with the gene present. No difference in the risk of cervical disease was associated with the GSTT1 null genotype. The combination of the CYP1A1 homozygous variant and the GSTM1 null genotypes increased the odds ratio for cervical SIL to 5.1 (95% CI = 1.3-20.7). There was no evidence for an interaction between genotype and exposure to tobacco smoke, alcohol drinking, or HPV DNA positivity. CONCLUSIONS: These findings, although based on a small number of subjects, suggest that the CYP1A1 MspI polymorphism may be a susceptibility factor for early, premalignant changes in the cervical epithelium.     

Human papillomavirus (HPV) testing in the management of women with abnormal Pap smears. Experience of a colposcopy referral clinic

BACKGROUND AND OBJECTIVES: Several detailed algorithms for the appropriate use of human papillomavirus (HPV) testing in the management of women with abnormal Pap (Papanicolaou) smears have been launched, but their direct country-to-country adoption is difficult. This necessitates their testing in individual settings, which is ongoing in our colposcopy referral clinic. METHODS: A series of 224 consecutive women attending the clinic with the usual referral indications (ASC-US or higher in Pap) were examined by the conventional diagnostic tools (PAP smear, colposcopy, punch biopsy) and subjected to HPV testing and viral typing for both low-risk (L-R) and high-risk (H-R) types by nested PCR-based techniques. Predictors of the high-grade diagnostic categories were analysed using both univariate- and multivariate modelling, and the performance characteristics (sensitivity, specificity, NPV, PPV) of all tests in detecting high-grade CIN were calculated. RESULTS: In the PAP test, ASC-US smears were most common (37.9%), followed by low-grade squamous intraepithelial lesions (LSIL) (26.3%) and high-grade SIL (HSIL) (4.9%). Colposcopy was performed for 180 women, of whom 48.3% had a normal transformation zone (TZ), 40.6% had ATZ1 (abnormal TZ grade 1), and 5.6% had ATZ2. In biopsy (n = 71), 49.3% had CIN1, 5.6% CIN2, and 16.9% CIN3. The HPV test was positive in 64 (28.8%) women, more often in those aged < 35 years (p = 0.025). High-grade colposcopy (ATZ2) was significantly associated with HSIL in the Pap test (OR 20.5; 95% CI: 4.34-96.47), and with HPV test positivity (OR 6.37; 95% CI: 1.58-25.73). The most significant predictors of CIN3 were HSIL in the PAP, HPV test positivity, and high-grade colposcopy. HSIL and HPV test (for H-R types), but not colposcopy, retained their significance as independent predictors of CIN3 also in adjusted multivariate models: OR 88.27; 95% CI 4.17-1867.04, and OR 19.46; 95% CI 2.01-187.75, for the HSIL and H-R HPV test, respectively. Changing the cut-off level of the Pap test from ASC-US to HSIL increased the specificity of the test up to 96.4%, with the loss in sensitivity from 87.5% to 43.8%. Colposcopy (ATZ2) had 92% specificity, and NPV competing with that of the Pap test. The sensitivity of HPV test exceeds that of the Pap test at HSIL cut-off level, but the specificity of the PAP test is clearly superior. CONCLUSIONS: Accurate predictors of significant cervical pathology (CIN3) are well defined, but the problem is the different performance of the diagnostic tools in clinical practice. A proficient combination of the tests is likely to result in the most satisfactory clinical practice in the management of women with abnormal Pap tests (MAPS).     

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.     

Human papillomavirus typing in HIV-positive women

OBJECTIVE: Human papillomavirus (HPV) is the major cause of cervical carcinoma and cervical intraepithelial neoplasia worldwide. Certain HPV types have a strong association with and probably a causative role in the pathogenesis of premalignant cervical lesions. Epidemiologic studies in women infected by the human immunodeficiency virus (HIV) have shown an increased incidence of squamous intraepithelial lesions (SILs), which were predominantly high-grade. Six to 30 per cent of women diagnosed with atypical squamous cells of undetermined significance (ASCUS) on a Papanicolaou (Pap) smear harbor SIL in normal screening populations. This study was undertaken to determine the presence of low-and high-risk HPV types in women infected by HIV and to correlate the results to those of the Pap smear. STUDY DESIGN: HPV DNA typing (low- and high-risk) by Digene (Digene Corporation, Gathesburg, MD) hybrid capture methodology was performed on cervical swabs from 209 HIV-positive women. The results of HPV typing were correlated with those of the Pap smear in a retrospective analysis. RESULTS: One hundred and one women (48%) tested positive for HPV subtypes by DNA typing by the hybrid capture method. Of these, 64 patients (63%) had Pap smears which were read as being normal, having benign cellular changes, or having ASCUS (favor reactive process). Of these, 19 patients tested positive for both high-risk and low-risk subtypes, 32 patients tested positive only for high-risk subtypes, and 13 patients tested positive only for low-risk subtypes. CONCLUSION: HPV subtyping identifies a significant group of HIV-positive women who are at risk for developing cervical intraepithelial neoplasia, although they may not show significant abnormalities on their Pap smears.     

Human papillomavirus testing in primary screening for cervical cancer of human immunodeficiency virus-infected women, 1990-1998

OBJECTIVE: Women infected with the human immunodeficiency virus (HIV) have an increased risk of cervical neoplasia while the value of cytologic screening is limited due to a high prevalence of inflammatory disease. The study was conducted to determine whether testing for human papillomavirus (HPV) DNA could improve primary screening for cervical cancer of these patients. METHODS: One hundred thirty-eight HIV-infected women were examined between 1990 and 1998. Ninety-four patients with a total of 279 women-years were eligible for incidence evaluation. Colposcopy, cytology, and HPV DNA testing with the hybrid capture I assay were performed at each visit. RESULTS: Seventeen cases of high-grade cervical neoplasia were diagnosed at study entry and 13 developed CIN II or CIN III during follow-up. The hybrid capture I assay detected 94.1% of prevalent and 100% of incident high-grade neoplasia, while the corresponding sensitivity of Pap smears using CIN I or worse as the referral criteria was 82.3% for prevalent and 69.2% for incident high-grade neoplasia. Eleven of 13 patients who progressed to histologically confirmed CIN II/III tested positive for HPV DNA at study entry compared with 5/13 women presenting with any degree of cytologic atypia at recruitment. The Pap smears of 36/94 women remained normal throughout the study while 54/94 patients remained negative for high-risk HPV types. CONCLUSION: Hybrid capture I identified high-grade cervical neoplasia more accurately than the Pap smear and appeared to be beneficial for primary cervical cancer screening in HIV-infected women.     

Lifetime cigarette smoke and second-hand smoke and cervical intraepithelial neoplasm--a community-based case-control study

BACKGROUND: Both active cigarette smoking and human papillomavirus (HPV) infection are known risk factors for cervical intraepithelial neoplasm (CIN). The association between second-hand smoke (SHS) and CIN has not been conclusively determined. We conducted a community-based case-control study to estimate the relationship between SHS and CIN. METHODS: Potential study subjects were selected through Pap smear screening in Kaohsiung County, Taiwan. A total of 171 subjects with either their first case of inflammation (benign epithelial lesion) or > or = CIN1 by biopsy confirmation were assigned to a case group; 513 normal subjects with negative findings by Pap smears or biopsies were assigned to a control group. RESULTS: Non-smoking women exposed to more than 20 pack-years of cigarette smoke had a significantly greater risk of developing > or = CIN2 than unexposed non-smokers (adjusted OR=7.2, 95% CI=2.5-20.6). Among the women without HPV infections, the greater the severity of disease found in the groups (normal, inflammation, CIN1, to > or = CIN2), the more likely it was for the women to be exposed to SHS, a significant increasing trend (p=0.037). CONCLUSIONS: In addition to HPV infection and active cigarette smoking, exposure to SHS is a major risk factor for CIN among Taiwanese women.     

Comparison of two signal-amplification DNA tests for high-risk HPV as an aid to colposcopy

OBJECTIVE: To compare Hybrid Capture Tube (HCT) and the second-generation Hybrid Capture II (HC II) test for detection of high-risk human papillomavirus (HPV) DNA at the time of colposcopy. STUDY DESIGN: Colposcopy and HPV testing were performed by HCT and HC II on 1,309 women for evaluation of abnormal Pap smears. Differences in the proportions were tested with chi 2 and 95% CI calculations. RESULTS: When compared to HCT, HC II was more often positive in women with any abnormal Pap smear (44% [95% CI 41-46%] vs. 34% [31-37%], P < .005) and in the subset of women with atypical squamous cells of undetermined significance Pap smears (32% [29-35%] vs. 24% [22-27%], P < .005). HC II was more sensitive in detecting cervical intraepithelial neoplasia (CIN) 2 or worse (93% [88-97%] vs. 78% [70-84%], P < .005) and had a lower rate of undetected > or = CIN 2 in HPV test-negative subjects (1.5% [0.7-2.7%]) vs. 4.3% [3.0-5.9%], P < .005). HC II was also more often positive in women with negative colposcopic evaluations (29% [25.7-32.4%] vs. 20% [17.6-23.5%], P < .005). The specificity of HC II in detection of > or = CIN 2 was lower than that for HCT (63% [60.5-66.2%] vs. 73% [69.5-74.8%], P < .005).     

Lack of evidence that proline homozygosity at codon 72 of p53 and rare arginine allele at codon 31 of p21, jointly mediate cervical cancer susceptibility among Indian women

OBJECTIVES: The objective of this study was to identify whether variants of p53Arg72Pro and p21Ser31Arg were associated with increased risk for cervical cancer (CaCx), either independently or jointly, among Indian women. METHODS: Genotyping was done by PCR-RFLP using DNA from (i) 120 cervical biopsy tissues of squamous cell carcinoma of the cervix (of which 82 were HPV16/18 positive), and (ii) a total of 205 cytologically normal cervical scrapes (121 HPV-negative and 84 HPV16/18-positive samples, considered as discreet groups). Multiple logistic regression analyses were performed to examine additive or interactive effects of the two factors and for determining age-adjusted OR (95% CI) and P values. RESULTS: The observed association of proline homozygosity at codon 72 of p53 with CaCx infection (Bhattacharya, P., Duttagupta, C., Sengupta, S. 2002.Proline homozygosity in codon 72 of p53: A risk genotype for Human Papillomavirus related cervical cancer in Indian women. Cancer Lett 188: 207-211) was retained among Indian women harboring HPV16/18 (OR(age-adjusted) = 3.76; 95% CI = 1.03-13.80; P = 0.04). Significant independent association was evident between the p21 arginine allele (rare allele with frequency of 0.1) at codon 31 and CaCx, compared to HPV-negative cytologically normal controls (OR(age-adjusted) = 2.01; 95% CI = 1.00-4.06; P = 0.05). The two risk factors jointly failed to show statistical interaction towards susceptibility to CaCx. The p21 arginine allele was significantly associated with CaCx in the p53 proline non-homozygous group of subjects (OR(age-adjusted) = 2.68; 95% CI: 1.21-5.91; P = 0.01), and specifically in the p53 heterozygous group (OR(age-adjusted) = 2.91; 95% CI = 1.12-7.56; P = 0.03). CONCLUSIONS: p53 and p21 act in series in mediating cell cycle arrest. However, the two risk factors, p53 proline homozygosity and p21 arginine allele, although part of a common causal pathway, appear to act in a mutually exclusive manner.     

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.     

Sociodemographic factors associated with high-risk human papillomavirus infection

OBJECTIVE: To determine the prevalence of high-risk (cancer-associated) human papillomavirus (HPV) infection in U.S. women, identify sociodemographic factors associated with infection, and explore the implications for prevention of HPV-related disease in the vaccination era. METHODS: Women aged 14-59 years (n=1,921) participating in the 2003-2004 National Health and Nutrition Examination Survey provided a vaginal swab which was evaluated for 37 HPV types. We determined which sociodemographic characteristics were associated with high-risk HPV, using logistic regression models. RESULTS: High-risk HPV infection was present in 15.6% (95% confidence interval [CI] 12.6-18.6%) of participants, corresponding to a population prevalence of 12,028,293 U.S. women. Women living below the poverty line, compared with those living three or more times above it, were more likely to be positive for high-risk HPV (23% versus 12%, P = .03). Among participants living below the poverty line, only Mexican-American ethnicity (odds ratio [OR] 0.4, 95% CI 0.2-0.9) and unmarried status (OR 3.3, 95% CI 1.2-8.9) were associated with HPV prevalence. In contrast, several factors were associated with HPV among participants living above the poverty line, including black race (OR 1.4, 95% CI 1.0-2.0), income (OR 0.92, 95% CI 0.84-0.99), unmarried status (OR 2.0, 95% CI 1.3-3.0), and age (OR for 22-25 year olds 2.4, 95% CI 1.4-4.0). CONCLUSION: High-risk HPV infection is common in U.S. women, particularly in poor women. Cervical cancer prevention efforts in the vaccination era must ensure that all low-income women have access to preventive services including education, Pap test screening, and HPV vaccines. Otherwise, existing disparities in cervical cancer could worsen.     

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.     

Social and cultural barriers to Papanicolaou test screening in an urban population

OBJECTIVE: To define screening behaviors, attitudes, and beliefs regarding cancer and its treatment among women with cervical cancer. METHODS: Between August 2000 and July 2002, 148 consecutive women with invasive cervical cancer were queried about barriers to screening. Women presented to outpatient clinics, emergency departments, or inpatient units of 3 urban hospitals. Two groups of women were identified: those who denied having had a Papanicolaou (Pap) test and those who had recalled having Pap test in the past. Responses were compared using t tests, chi(2) tests, and binary logistic regression. RESULTS: The 146 (99%) respondents were predominantly African Americans (50%) or Hispanic (27%). Thirty-six (25%) women reported no prior screening. Women never screened were significantly more likely to be Hispanic (odds ratio [OR] 3.0, 95% confidence interval [CI] 1.4-6.7), recent immigrants (OR 5.7, 95% CI 2.0-16), less educated (OR 3.6, 95% CI 1.6-8.0), and uninsured (OR 3.9, 95% CI 1.6-9.7). They were more likely to lack family support (adjusted OR 3.5, 95% CI 1.1-11) and lack knowledge about their risk for cervical cancer (adjusted OR 2.6, 95% CI 1.1-6.4). Unscreened women displayed fatalistic attitudes, believing cancer is bad luck (adjusted OR 2.6, 95% CI 1.0-6.9) and not wanting to know they had cancer (adjusted OR 3.0, 95% CI 1.0-9.4).. CONCLUSION: We have identified factors and beliefs that are barriers to Pap test screening in urban cervical cancer patients. Further studies should evaluate effects of addressing cultural, cognitive, and financial barriers on Pap test compliance.     

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.     

A population-based study of squamous cell vaginal cancer: HPV and cofactors.

BACKGROUND: Little is known about the etiology of in situ or invasive squamous cell cancer of the vagina. It is thought that some vaginal cancers may have the same etiology as cervical cancer. It is also not known whether in situ and invasive vaginal cancer share the same etiologic factors. We conducted a study to evaluate risk factors for in situ and invasive vaginal cancer and their potential relationship to prior exposure to human papillomaviruses (HPV). METHODS: A population-based case-control study included 156 women with squamous cell in situ or invasive vaginal cancer diagnosed between January 1981 and June 1998 and 2041 control women identified through random-digit dialing in western Washington state. Cases and controls were interviewed in person and provided blood samples; archival tumor tissue was retrieved for cases. Blood samples were tested for antibodies to HPV, and tumor tissue was tested for HPV DNA. RESULTS: Women with vaginal cancer were more likely to have five or more lifetime sexual partners (OR = 3.1, 95% CI 1.9 to 4.9), to have an early age at first intercourse (<17 years OR = 2.0, 95% CI 1.2 to 3.5), and to be current smokers at diagnosis (OR = 2.1, 95% CI 1.4 to 3.1) than control women. Approximately 30% of all cases had been treated for a prior anogenital tumor, most often of the cervix. Prior hysterectomy was a risk factor only among women who had no history of prior anogenital cancer (OR = 3.9 95% CI 2.5 to 6.1). Antibodies to HPV16 L1 were strongly related to risk of vaginal cancer (OR = 4.3, 95% CI 3.0 to 6.2). We detected HPV DNA in tumor blocks from over 80% of the patients with in situ and 60% of the patients with invasive cancers. CONCLUSIONS: In situ and invasive vaginal neoplasia have many of the same risk factors as cervical cancer, including a strong relationship to HPV infection. Women who have been treated for a prior anogenital cancer, particularly of the cervix, have a high relative risk, although low absolute risk, of being diagnosed with vaginal cancer.     

Human Papillomavirus Testing in Primary Screening for Cervical Cancer of Human Immunodeficiency Virus-Infected Women, 1990–1998

Objective. Women infected with the human immunodeficiency virus (HIV) have an increased risk of cervical neoplasia while the value of cytologic screening is limited due to a high prevalence of inflammatory disease. The study was conducted to determine whether testing for human papillomavirus (HPV) DNA could improve primary screening for cervical cancer of these patients.Methods. One hundred thirty-eight HIV-infected women were examined between 1990 and 1998. Ninety-four patients with a total of 279 women-years were eligible for incidence evaluation. Colposcopy, cytology, and HPV DNA testing with the hybrid capture I assay were performed at each visit.Results. Seventeen cases of high-grade cervical neoplasia were diagnosed at study entry and 13 developed CIN II or CIN III during follow-up. The hybrid capture I assay detected 94.1% of prevalent and 100% of incident high-grade neoplasia, while the corresponding sensitivity of Pap smears using CIN I or worse as the referral criteria was 82.3% for prevalent and 69.2% for incident high-grade neoplasia. Eleven of 13 patients who progressed to histologically confirmed CIN II/III tested positive for HPV DNA at study entry compared with 5/13 women presenting with any degree of cytologic atypia at recruitment. The Pap smears of 36/94 women remained normal throughout the study while 54/94 patients remained negative for high-risk HPV types.Conclusion. Hybrid capture I identified high-grade cervical neoplasia more accurately than the Pap smear and appeared to be beneficial for primary cervical cancer screening in HIV-infected women.