Risk Of Cervical Intraepithelial Neoplasia Research Articles

Cigarette smoking and high-risk HPV DNA as predisposing factors for high-grade cervical intraepithelial neoplasia (CIN) in young Brazilian women.

This cross-sectional study was designed to evaluate the role of cigarette smoking and high-risk HPV types as risk factors of CIN 2 and 3 in young, sexually active Brazilian women. A series of 100 consecutive women with abnormal Pap smears were recruited, subjected to colposcopy, punch biopsy, and questionnaire for their social, sexual and reproductive factors. Of these, 77 women between 20 and 35 years of age (median 26.5 years) with biopsy-confirmed CIN 1 or CIN 2 and 3, were enrolled in this study. Representative samples from the exocervix and endocervix were obtained for HPV testing with the Hybrid Capture HPV-DNA assay, including the probes for the oncogenic HPV types (16, 18, 31, 33, 35, 45, 51, 52 and 56). The overall rate of CIN 2 and 3 was 23/77 (29.8%). The women with CIN 1, 2 and 3 did not differ from each other with regard to their age, race, schooling, marital status, lifetime number of sexual partners, age at first intercourse, use of oral contraceptives, or parity. However, current cigarette smoking was strongly associated with CIN 2 and 3 (p<0.001), and among smokers, the risk of high-grade CIN increased in parallel with the time of exposure (years of smoking) (p=0.07). HPV-DNA of the oncogenic types was detected in 43 (56%) women, the risk of being HPV DNA-positive was significantly higher in CIN 2 and 3 as compared with CIN 1 (p=0.037). Importantly, the prevalence of high-risk HPV types was significantly higher in cigarette smokers than in non-smokers (p=0.046). The results indicate that the severity of CIN lesions was clearly related to two fundamental risk factors: 1) high-risk HPV types, and 2) current cigarette smoking. These two risk factors were closely interrelated in that the high-risk HPV types were significantly more frequent in current smokers than in non-smokers, suggesting the possibility of a synergistic action between these two risk factors in cervical carcinogenesis.

Adequacy of Screening Cervical Cytology among Human Immunodeficiency Virus-Seropositive Women

Objective.To evaluate the adequacy of cytology in detecting cervical intraepithelial neoplasia (CIN) among human immunodeficiency virus (HIV)-seropositive women compared to controls.Methods.A cross-sectional study was carried out evaluating 241 HIV-seropositive women and 991 controls (404 HIV seronegative and 587 of unknown HIV status) at risk for CIN attending a vaginitis clinic. All patients had a Pap smear and a standard colposcopic examination of the lower genital tract. Cervical biopsies were taken as indicated by colposcopy. Cytology and histology slides were read by a cytopathologist blinded to patients' serostatus. False-negative cytologic cases were reviewed by three independent cytopathologists to estimate sampling and screening error rates. Sensitivity, specificity, and false-negative rate of cytologic smears were compared between HIV seropositives and controls. We estimated the sampling and screening error rates among cases with false-negative cytology.Results.Among seropositives, the sensitivity, specificity, and the false-negative smear rate for CIN were 73.4% (47/64), 97.1% (134/138), and 26.6% (17/64), respectively. The corresponding figures in controls were 83.8% (83/99), 99.04% (825/833), and 16.2% (16/99), respectively, and did not differ significantly from those of seropositives. The negative predictive value of cytology was lower among seropositives (134/151) than in controls (825/841, χ2= 34.8,P< .001). The agreement between cytologic readings and combined colposcopy and histology was stronger among controls (kappa = 0.789, 95% CI 0.723 to 0.856) than among seropositives (kappa = 0.593, 95% CI 0.475 to 0.712). Three independent cytopathologists were unable to detect atypical cells in 52.9% (9/17) of false-negative smears taken from seropositive women as opposed to 37.5% (6/16) of controls.Conclusions.The sensitivity, specificity, and false negative rate of screening cytology for CIN among HIV seropositive women are comparable with those in the general population. Since almost 50% of false-negative results could be attributed to sampling errors, more frequent cytological screening may prove to be beneficial to this high-risk group.

Association of decreased cervicovaginal cell ascorbic acid levels with increased risk of Cervical Intraepithelial Neoplasia (CIN)

Association of decreased cervicovaginal cell ascorbic acid levels with increased risk of Cervical Intraepithelial Neoplasia (CIN)

Genomic variation of human papillomavirus type 16 and risk for high grade cervical intraepithelial neoplasia.

Epidemiologic studies have demonstrated strong and consistent associations between the detection of human papillomavirus (HPV) type 16 DNA and the risk of cervical intraepithelial neoplasia (CIN) and cervical cancer. However, HPV16 is also the most common type of HPV in the normal population, and only a minority of women with HPV16 infection develop cervical cancer. Studies of genomic heterogeneity in HPV16 have demonstrated the presence of multiple variant forms in all human populations examined to date. It is conceivable that the natural variants of HPV16 in a given population may not have the same biologic behavior. This study was designed to determine the association between natural variants of HPV16 and the risk of biopsy-confirmed CIN 2 or 3, the most important precancerous lesions of the uterine cervix. Prospective studies were conducted among 1) women attending a university and 2) women presenting to a sexually transmitted disease clinic. Subjects were eligible for inclusion in this investigation if the initial cytologic findings did not reveal CIN 2-3 and HPV16 DNA was detected by means of a polymerase chain reaction (PCR)-based method in one or more cervical or vulvovaginal samples. Eligible subjects were followed every 4 months with cervical Pap smears and colposcopic examinations. Women were referred for biopsy if cytology or colposcopy suggested CIN 2-3. Two groups of HPV16 variants, prototype-like and nonprototype-like, were determined by means of single-strand conformation polymorphism (SSCP) analysis of PCR products from the noncoding region of the viral genome. Representative SSCP patterns from HPV16 variants were further characterized by direct DNA sequencing of the PCR products. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated by Cox regression analysis. Prototype-like variants accounted for 79% of the HPV16 detected in university students and 86% of the virus detected in patients presenting to the sexually transmitted disease clinic. CIN 2-3 was confirmed by biopsy in nine of 57 HPV16-positive women attending the university and in 10 of 66 HPV16-positive women presenting to the sexually transmitted disease clinic. Among university students, those with HPV16 nonprototype-like variants were 6.5 (95% CI = 1.6-27.2) times more likely to develop CIN 2-3 than those with prototype-like variants. A similar association was observed among women presenting to the sexually transmitted disease clinic (RR = 4.5; 95% CI = 0.9-23.8). This study suggests that the risk of developing CIN 2-3 is not the same with all variants of HPV16 and that nonprototype-like variants confer a greater risk compared with prototype-like variants. The important genomic differences underlying this increased risk of CIN 2-3 remain to be determined.

A prospective study on the risk of cervical intra-epithelial neoplasia among healthy subjects with serum antibodies to HPV compared with HPV DNA in cervical smears.

To estimate the risk of developing cervical intra-epithelial neoplasia (CIN) among women exposed to human papillomavirus (HPV) type 16, we performed a prospective study in a population-based cohort of more than 15,000 women followed for 34.9 months. Seventy-four women developed CIN during follow-up and were matched for age, time of sampling and area of residence with 148 women who remained CIN-free during follow-up. The blood samples taken at enrollment were tested for serum antibodies to HPV types 16, 18 and 33 capsids. Cervical smears or biopsies were analyzed for the presence of HPV DNA by nested PCR using HPV general primers and by HPV 16- and 18-type-specific PCR HPV serology and HPV-PCR were in good agreement, particularly when the blood sample and the Pap smear were taken less than 6 months apart. HPV DNA was found in 88% of cases and 4% of controls, whereas HPV 16 DNA was present in 44% of cases and in 1 of 142 controls. HPV-16-seropositive women had a 3-fold increased risk of developing CIN. The risk was highest among women younger than 35 years of age, of whom an estimated 3.4% of HPV-16-seropositive and 0.5% of seronegative women developed CIN. Since the risk associated with HPV-16 seropositivity (a measure of past or present infection) was 35-fold lower than that of HPV DNA (present infection), most infections appear to be eliminated before CIN develops. In conclusion, HPV 16 infection does confer an excess risk of CIN development, and HPV DNA detection has a high predictive value for the presence of high-grade CIN.

Susceptibility to human papillomavirus-associated cervical intra-epithelial neoplasia is determined by specific HLA DR-DQ alleles.

Human papillomaviruses (HPV) play a causative role in the aetiology of cervical intra-epithelial neoplasia (CIN) and cervical cancer. Human leukocyte antigens (HLA) are important in the regulation of immune response to foreign antigens. The role of genetic variation at the HLA class II loci (DR and DQ) in CIN (HPV 16, 18, 31 and 33 typed) was investigated by PCR DNA amplification and oligonucleotide probe typing of cervical smears from British Caucasian patients (n = 176) and controls (n = 416). The alleles of the DQB1*03, DRB1*04 and DRB1*11 loci were strongly associated with susceptibility to CIN. Specifically, the haplotypes DRB1*0401-DQB1*0301 and DRB1*1101-DQB1*0301 were significant and indicated susceptibility. The DQB1*03 locus was more contributory to this association than the DRB1 loci. A weak protective effect was shown for the haplotype DRB1*0101-DQB1*0501. Positive correlation was also observed for HPV-positive CIN, suggesting that specific HLA class II alleles may be important in determining the immune response to HPV antigens and the risk for CIN after HPV infection. Our results should help in the rational design of vaccines against HPV.

Cervical intraepithelial neoplasia in pregnant intravenous drug users infected with human immunodeficiency virus type 1

Objective: The purpose of this study was to evaluate the frequency and natural history of cervical intraepithelial neoplasia (CIN) during pregnancy in past or current intravenous drug users infected with human immunodeficiency virus type 1 (HIV-1). Study design: We prospectively evaluated 48 pregnant HIV-1 seropositive patients and 38 HIV seronegative controls. All the subjects were current or past intravenous drug users. Follow-up visits were carried out each trimester of pregnancy and 8–12 weeks post-partum with Papanicolau smears, colposcopic examinations and, when necessary, colposcopically directed cervical biopsies. Results: Thirteen of 48 HIV-seropositive women (27.1%) and three of 38 HIV-seronegative controls (7.9%) ( P = 0.027 by Fisher exact test) had biopsy-proven CIN at the beginning of pregnancy. High-grade CIN was detected in 10 cases (20.8%) and in two (5.3%) controls ( P = 0.058 by Fisher exact test). None of the cervical squamous intraepithelial lesions progressed throughout pregnancy, in both cases and controls. Post-partum cold-knife cervical conization was performed on seven patients with CIN III and examination of the cone biopsy specimens demonstrated persistence of CIN III. Conclusions: HIV-infected intravenous drug users are at high risk of CIN during pregnancy, thus requiring adequate screening programs. Our preliminary data suggest that the progression rate of CIN during gestation is low in this high-risk group.

Low prevalence of human papillomavirus infection of the cervix in renal transplant recipients

An increased risk of anogenital tract malignancies has been noted among renal transplant recipients. A high prevalence of human papillomavirus (HPV) infection of the cervix in the female renal-transplant population has been assumed based on increasing evidence suggesting that HPV infection is the major risk factor for cervical intraepithelial neoplasia (CIN) and cervical cancer. It has been assumed that immunosuppression leads to either a reactivation of latent HPV or a reduction in the host's ability to contain a primary HPV infection, thereby increasing the risk of CIN and cervical cancer. The objective of this study was to evaluate the prevalence of human papillomavirus (HPV) infection in a population of iatrogenically immunosuppressed renal transplant recipients. Twenty-one women were recruited from the renal transplant clinic at Presbyterian Hospital and underwent a gynaecological examination which included colposcopy, a Papanicolaou smear, and a cervicovaginal lavage. Lavage samples were analysed for HPV DNA using L1 consensus primers and the polymerase chain reaction (PCR). No cases of cervical intraepithelial neoplasia (CIN) were detected in this cohort of 21 immuno-suppressed renal transplant recipients. HPV DNA was detected in only a single patient. Our data suggests that HPV infection is not highly prevalent among older, cytologically normal renal transplant recipients, particularly those who are currently monogamous or not presently sexually active. This study suggests that recent sexual behaviours are more important than past behaviours as a determinant of HPV status in transplant recipients, and also suggests that education concerning the avoidance of high-risk sexual behaviour is an important part of the care of the female renal transplant recipient. Our data is consistent with previous work suggesting that the incidence of CIN is declining in transplant recipients, and it also suggests that the prevalence of HPV infection may be declining as well.

Koilocytosis; an indication for conservative management.

The management of women with mild dyskaryosis continues to be the subject of debate. The management of cases with such smears could be improved if additional morphological features were found to be indicative of low/high grade cervical intraepithelial neoplasia (CIN). Our own experience in the routine audit of the diagnostic accuracy of cervical smears had suggested that cases of dyskaryosis with koilcytosis were associated with low risk of CINIII. Two hundred and forty-four cervical smears reported as showing evidence of warty virus infection were reviewed and their subsequent histories noted. Of these smears, 173 demonstrated clear evidence of koilocytosis. Irrespective of the initial grade of dyskaryosis, only 28 cases (16.2%) had underlying CIN or had progressed to CIN over a minimum follow-up period of 21 months. Only two cases (1.2%) showed evidence of CINIII. Koilcytosis is associated with a low risk of CIN and an especially low risk of CINIII. The management of women with koilocytic smears should be modified accordingly.

Cervical neoplasia in pap smears: risk of cervical intra-epithelial neoplasia (CIN) after negative or no prior smears in a population without a mass screening programme.

The aim of this study was to examine, in a population not submitted to mass screening, the risk of cancer and cervical intra-epithelial neoplasia (CIN) in Pap smears from women without previously reported positive smears. In a logistic regression model consisting of 58,271 smears from 40,536 Norwegian women the risk of cytologically indicated CIN was studied according to age and time elapsed since last smear. The risk of CIN was highest in smears from women with no previously registered smears and in smears taken after an interval of > or = 5 years. Odds ratio for CIN I-II adjusted for age was highest in first time smears and in smears taken after an interval of 5 years. Odds ratio for CIN III was highest in first registered smears. No difference in risk of CIN III was found in smears taken within one year or 2-3 years after the last smear. The increased risk of CIN III in first smears was most pronounced in postmenopausal women ( > 50 years). Nine of 16 cases with cytological indication of cancer were found in women having a smear taken for the first time. All cases with malignancy in smears were > 50 years. The risk of cytologically diagnosed premalignant cervical conditions increases with time since the previous smear, but more than 5 years have to elapse before the risk is comparable with that in first smears taken. Postmenopausal women without previous smears run the highest risk of serious cervical premalignancies and cancer.

Determinants of high-grade dysplasia among women with mild dyskaryosis on cervical smear

To identify the epidemiologic characteristics of women who have mild dyskaryosis on cervical smear but cervical intraepithelial neoplasia (CIN) grade II or III at biopsy. We analyzed information from 291 women (median age 33 years, range 17-69) observed for the first time with a single smear test showing mild dyskaryosis. All subjects underwent colposcopy, and histologic confirmation was obtained by biopsy. We compared the characteristics of women who had CIN I or no evidence of CIN with those of women with CIN II or III at biopsy. Twenty-eight women (10%) had CIN I at biopsy, 46 (15%) CIN II, and 23 (8%) CIN III. The frequency of CIN II or III tended to decrease with increasing education; compared with women reporting 11 or fewer years of education, the multivariate odds ratios (OR) of CIN II or III lesions was 0.5 (95% confidence interval [CI] 0.3-0.9) in those reporting 11 years of education or more. Compared with nulliparas, the OR of CIN II or III was 1.8 (95% CI 1.1-3.5) for parous women. Furthermore, compared with never-smokers, the OR of CIN II or III was 2.3 (95% CI 1.0-5.4) for current smokers. Ex-smokers were at increased risk, too; the estimated multivariate OR was 3.8 (95% CI 1.9-7.6). Compared with women reporting one sexual partner, the multivariate ORs of CIN II or III were 1.4 and 2.3 for women reporting two to three or four or more sexual partners, respectively (chi 2(1) trend = 6.65, P < .05). Our results show that smoking is a risk indicator of CIN II or III in women with a single smear showing mild dyskaryosis. Parous women, those of low social standing, and those reporting multiple sexual partners also are at increased risk of CIN II or III.

Cervical Intraepithelial Neoplasia in Jordan: A Ten Year Retrospective Cytoepidemiologic Study

Occurrence of cervical intraepithelial neoplasia (CIN) was studied in 10,659 females attending obstetric and gynecology clinics in Jordan. The frequency rate of intraepithelial neoplasia was 1.1% in 7743 Jordanian females and 2916 non-Jordanian residents of younger age during the period from 1982 to 1991 inclusive. The incidence rate in 2649 Jordanian females, selected because they attended only for routine checkup, was 49 per 100,000. There were 121 CIN cases which were graded into Grade I (21%), II (48%) and III (31%) respectively. Histological grading correlated with cytology in 70% of the cases while in the remaining 30%, cytologic underrating by one grade was noted; evidence against any overdiagnosis of CIN in our series. Study of the human papillomavirus (HPV) was outside the scope of this effort. However, circumcision in male partners and marital status were associated with a lower frequency of CIN. Age at marriage and average duration, parity, breast feeding, the contraceptive pill, socioeconomic status and menstrual disorders showed no relationship to the frequency of CIN in our patients. Any differences in the latter between Jordanian and non-Jordanian females are believed due to cultural factors. Conization in 27 cases proved effective at 30 months' follow-up. Occurrence of CIN in Jordanian females appears substantial although much lower than that seen in high incidence zones, while its incidence in the general female population remains to be determined. This study shows for the first time the value of Papanicolaou (Pap) smears in Jordanian females over 20 years of age with special emphasis on those over 35 years of age attending obstetric and gynecology clinics.

Pill Use Appears Likely To Increase Risk of Some Forms of Cervical Cancer

Two recent case-control studies suggest that the risk of cervical cancer may be increased by oral contraceptive (OC) use. The first involving 195 women from Los Angeles California who had been diagnosed with adenocarcinoma of the cervix in 1977-91 and 386 matched controls found that ever-use of OCs doubled the risk of cervical cancer (odds ratio 2.1). The risk was highest (4.4) among women who had used OCs for more than 12 years. Once duration of OC use was controlled there was no additional cancer risk associated with age at initiation of OC use duration of OC use before 20 years of age or before first pregnancy time since first or last OC use type of pill taken and frequency of Pap smears. The second study involving 2168 women recruited from a colposcopy clinic in Quebec Canada in 1988-89 identified 548 women with at least one late-stage cervical intraepithelial neoplasia (CIN) and 338 women with early-stage CIN. 612 women with no signs of neoplasia cervical cancer or human papillomavirus (HPV) served as controls. Ever-users of OCs had a 40% increased risk of late-stage CIN compared with never-users. Women who had used OCs for six or more years were almost twice as likely (relative risk 1.9) to have late-stage CIN while those who had used OCs for less than two years were at no elevated risk (0.9). The risk of early-stage CIN was not affected by OC use regardless of duration. Late-stage CIN was also strongly associated with smoking (relative risks of 2.4 among current and 1.3 among former smokers). Risks of both early and late-stage CIN were at least doubled among women with four or more lifetime sexual partners. Most significant however was the association with past HPV infection; these women were 8.7 times as likely as those not infected to have late-stage CIN. It remains unclear whether smoking and OC use affect initiation of late-stage CIN in the absence of HPV or whether they accelerate the progression of early-stage CIN or subclinical HPV to late-stage lesions.

Cervical cancer and herpes simplex virus type 2: Case‐control studies in Spain and Colombia, with special reference to immunoglobulin‐G sub‐classes

Two case-control studies, including 449 histologically confirmed cases of cervical intra-epithelial neoplasia (CIN) III and 425 controls, and 2 studies on invasive cervical cancer, involving 316 histologically confirmed cases and 330 population controls, were conducted in Colombia and Spain to assess the role of herpes simplex virus type 2 (HSV-2) in cervical neoplasia. Antibodies to this virus were also measured in the sera of 931 husbands of cases and controls. A serological assay using type-specific antigens, glycoprotein C for type I (gC-I) and glycoprotein G for type 2 (gG-2) was employed. Immunoglobulin-G (IgG) sub-classes, IgG1 and IgG3, were measured in women positive for HSV-2 antibodies. No increase in risk of CIN III or invasive cancer was found in women whose sera or whose husbands' sera were positive to HSV-2. However, compared with women negative to HSV-2, the risk of CIN III progressively increased with increasing levels of IgG1. The trend was statistically significant in Colombia. There was also a statistically significant increasing trend in risk of invasive cancer with levels of IgG1 in Spain. The levels of IgG3 and its ratio to IgG1, which may indicate recurrent infections, were not associated with the risk of either type of cancer. When the association with IgG1 was analyzed by human papillomavirus (HPV) DNA status, as determined by polymerase chain reaction, the trend was clearer in women whose HPV status was not determined or in those with negative HPV DNA. These results suggest that the role of HSV-2 is merely marginal and do not support the hypothesis that recurrent HSV-2 infections are of importance for cervical neoplasia.

Cancer-Associated Human Papillomaviruses

Pakarian, Farzin; Kaye, Jeremy; Cason, John; Kell, Barbara; Jewers, Richard; Derias, Nawal W.; Raju, Kankipati S.; Best, Jennifer M. Author Information

Association Between HLA DQBl * 03 and Cervical Intra-epithelial Neoplasia

Cervical intraepithelial neoplasia (CIN) and cervical cancer have been shown to be strongly associated with infection by human papillomavirus (HPV). However, other factors may be contributory in the progression from normal epithelium to CIN and cervical cancer, since not all women with HPV infection develop disease. Recently, it was demonstrated that there is a high risk for cervical cancer and CIN in women with HLA DQB1 * 03 (RR = 7.1, p < 0.0009) (1). Subsequent reports have been conflicting, due to sample size, genetic heterogeneity and differences in the techniques employed for the detection of HLA DQB1 * 03. DNA from cervical smears of 178 women with CIN and 420 controls with normal cervical cytology was analyzed by polymerase chain reaction (PCR) with type-specific primers for HPV 16, 18, 31, and 33. The DNA from test and control samples were also analyzed by a novel PCR technique, which mutates the first base of codon 40 (DQ alleles) from T to G to create an artificial restriction site for an enzyme Mlu I that distinguish DQB1 * 03 from other alleles and are confirmed by digestion of amplified DNA with Mlu I. Further analysis of individual DQB1 * 03 alleles was performed using PCR and allele-specific primers. One hundred forty-four (34%) out of 420 controls (all HPV 16, 18, 31, or 33 negative and normal cytology), 37/66 (56%) of CIN I and 72/112 (64%) of CIN III were positive for DQB1 * 03 (trend test, p < 0.001, chi 2 = 37.3). A significant association was observed between DQB1 * 03 and CIN (odds ratio 3.03; 95% CI 2.11-3.45). Of women with CIN, 131/178 (73.5%) had HPV (types 16, 18, 31, or 33) infection. There was a significant association between DQB1 * 03 and presence of HPV (odds ratio 3.43; 95% CI 2.25-5.10). Homozygosity for DQB1 * 03 was more strongly associated with CIN than heterozygosity (odds ratios 4.0 and 2.63, respectively); and for the presence of HPV (odds ratio 4.47; 95% CI 2.58-7.77). HLA DQB1 * 0301 was the most strongly associated allele with CIN and HPV (odds ratios 2.53 and 2.63, respectively). HLA DQB1 * 03 is associated significantly with CIN and may be permissive for HPV infection. Further analysis of class II HLA typing in CIN is necessary to evaluate this association.

Risk Factors for Cervical Intraepithelial Neoplasia: Differences between Low- and High-grade Lesions

This case-control study assesses relations of human papillomavirus (HPV) type 16 infection, sexual history, cigarette smoking, and oral contraceptive use to low- and high-grade cervical intraepithelial neoplasia (CIN). A total of 548 high-grade and 338 low-grade CIN cases and 612 controls were identified among women seen at a colposcopy clinic in Quebec, Quebec, Canada, in 1988-1989. Interviews, colposcopy, cervical scrapings, and colposcopically directed biopsies were performed. One pathologist reviewed all histologic slides. Southern blot techniques were used to assay specimens for HPV 16 DNA. Lifetime number of sexual partners was related to low- and high-grade CIN. Presence of HPV 16 DNA was associated with a 8.7-fold (95% confidence interval 5.1-15.0) elevation in estimated relative risk of high-grade CIN. Relative risk of high-grade CIN increased with amount of HPV 16 DNA (p < 0.0001). Estimated relative risk of high-grade CIN in current cigarette smokers was 2.4 (95% confidence interval 1.8-3.2) compared with never smokers and increased with number of pack-years of exposure (p < 0.0001). Long-term (6 years or more) users of oral contraceptives had an estimated relative risk of high-grade CIN of 1.9 (95% confidence interval 1.1-3.3) compared with those who never used such contraceptives. In contrast, presence of HPV 16 DNA, cigarette smoking, and oral contraceptive use showed little or no relation to low-grade CIN. Risk factors for low- and high-grade CIN may differ substantially.

Cancer associated human papillomaviruses: perinatal transmission and persistence.

To demonstrate the perinatal transmission and persistence of the cancer associated human papillomavirus types 16, 18, 31 and 33. Cervical swabs were taken from pregnant women between 20 and 38 weeks of gestation. Buccal and genital swabs were taken from infants at 24 h and at six weeks after delivery and examined for HPV-16, -18, -31 and -33 DNA by the polymerase chain reaction. Maternity Unit at St Thomas's Hospital, London. Thirty-one pregnant women, 16 with a previous history of cervical intraepithelial neoplasia or genital warts, or both, and their 32 infants (one set of twins). Twenty of the 31 (65%) women were positive for HPV-DNA prior to delivery. Twelve of 32 (38%) and eight of 31 (26%) infants were HPV-DNA positive at 24 h and six weeks respectively. Swabs taken at 24 h demonstrated HPV type 16 in five mother-infant pairs and HPV type 18 in two mother-infant pairs. Dual infections with HPV types 16 and 18 were demonstrated in swabs from three mother-infant pairs. At six weeks, HPV-16 was demonstrated in swabs from six infants and HPV-18 in swabs from two infants. Perinatal transmission of human papillomavirus types 16 and 18 occurred in 55% cases. Persistent human papillomavirus infection was demonstrated at six weeks of age. Whether acquisition of human papillomavirus during the perinatal period predisposes to an increased risk of cervical intraepithelial neoplasia among female infants in later life remains to be established. Information on the persistence of perinatally acquired human papillomavirus is required before rational vaccination programmes can be considered.

HPV, HIV infection, and risk of cervical intraepithelial neoplasia in former intravenous drug abusers

Abstract The relation between human immunodeficiency virus (HIV), human papilloma virus (HPV) infection, sexual habits, reproductive history, and risk of cervical intraepithelial neoplasia (CIN) has been analyzed in a cross-sectional study conducted since 1986 among female former intravenous drug abusers attending for the first time to the Colposcopic Unit of the Ospedale Luigi Sacco of Milan and women consecutively admitted to the Community for Past Drug Abusers, S. Patrignano, Rimini. A total of 434 subjects entered the study: of those 128 (30%) had a diagnosis of CIN. Compared with HIV-negative subjects, odds ratio (OR) of CIN was 8.0 (95% confidence interval (CI) 4.6-14.1) for HIV-positive ones and the frequency of CIN 2 and 3 was higher in HIV-positive than that in HIV-negative subjects (χ 2 1 trend, 6.67, P 0.01). Compared with women without current HPV infection the OR estimate was 38.0 (95% CI 20.3-71.2) in those with current diagnosis of HPV infection. Considering HIV-positive subjects only, the frequency of CIN increased with stage of HIV infection and was higher in women with lower CD4 + values. Finally, no relation emerged between CIN risk and age, indicators of sexual habits, oral contraceptive use, parity, and history of spontaneous or induced abortions.

Design and analysis considerations in a cohort study involving repeated measurement of both exposure and outcome: the association between genital papillomavirus infection and risk of cervical intraepithelial neoplasia.

Cohort studies commonly involve a single determination of exposure, and one or more assessments of whether or not the outcome of interest has occurred. This approach is appropriate when the exposure does not change with time, and when one can readily determine the time of outcome (for example, mortality). If either of these conditions is not met, however, we may introduce bias into the estimate of effect, since we may misclassify individual members of the cohort with respect to exposure, outcome or both. We can reduce this bias by measuring exposure and outcome on more than one occasion. In this paper, we illustrate the design and analysis issues that arise in such circumstances, by reference to an ongoing prospective study of the relationship between genital papillomavirus infection and risk of cervical intraepithelial neoplasia. This study entails annual assessments of the status of the study subjects with respect to both conditions. In particular, we examine the implications that use of this design has on the statistical power of the study.