Risk Factors For Cervical Neoplasia Research Articles

More isn’t always better: Risk of recurrent high-grade squamous intraepithelial lesions after single-pass loop electrosurgical excision procedure (LEEP) versus LEEP with top hat (398)

<b>Objectives:</b> The preferred treatment for high-grade intraepithelial neoplasia (HSIL) is the excisional procedure. Single-pass LEEP (LEEP- SP) and LEEP with a top hat (LEEP-TH) are commonly used excisional procedures. There is limited evidence to show the superiority of one surgical technique to another in terms of treatment failure. The objective of this study was to determine the risk of recurrent HSIL at two years after LEEP-SP versus LEEP-TH. <b>Methods:</b> Following IRB approval, this single-institution retrospective cohort study included all patients undergoing LEEP-SP or LEEP-TH for HSIL between 2005 and 2019. Patient demographics and risk factors for cervical neoplasia were collected along with preoperative cytology and colposcopy results. Follow-up cytology, colposcopy, and repeat surgical excision data were collected over a two-year follow-up period. Qualitative and quantitative analyses of the two patient cohorts were performed using descriptive statistics, Chi-squared or Fischer's exact for categorical variables, and Mann- Whitney U test for continuous variables using IBM SPSS Statistics (version 28.0.0.0). <b>Results:</b> A total of 340 patients met the inclusion criteria; 178 patients underwent a LEEP-SP, and 162 patients underwent a LEEP- TH. Patients undergoing LEEP-TH were more likely to be older (mean age: 40.40 +/- 10.13 years vs 36.49 +/- 10.45 years; p < 0.001), and have had a positive pre-procedure endocervical sampling ECS (68.5% vs 11.8%; p < 0.001). HSIL histology was found in 126 patients undergoing LEEP-SP (70.7%) and in 125 patients who underwent LEEP-TH (74.4%; p=0.182). Positive margins were found in 23 patients who underwent LEEP-SP (12.9%) and 25 who underwent LEEP-TH (15.4%; p=0.507). There was no significant difference in depth of excision between LEEP-SP and LEEP-TH (13.21+/- 23.19 mm vs 17.37 +/- 28.26 mm; p=0.138). In eight (4.9%) patients undergoing LEEP-TH, the initial pathology of the first pass specimen was benign, and only the top hat had HSIL. Only two (25%) of those patients also had a positive ECS. At two years follow-up, there was no difference in the rates of HSIL cytology (7 patients [5.2%] vs 8 [6.3%]), any positive HPV test or HSIL cytology (27 patients [25%] vs 19 [15%]), or repeat excision (11 patients [8.9%] vs 16 [12.4%]) between LEEP-SP and LEEP-TH. Repeat excision was performed in 27 patients, who were more likely to be older (mean age: 42.26 +/- 10.75 years vs 36.77 +/- 10.36 years; p=0.016) and have initial cytology HSIL (63.0% vs 33.3%; p=0.003), compared to patients who did not undergo repeat excision. <b>Conclusions:</b> In this single-institution study, there is no difference in the rate of recurrent HSIL or repeat excision in patients who undergo LEEP-SP compared with LEEP-TH. Additionally, there appears to be no difference in the rate of positive margins or positive ECS at the time of excision between the two groups. This suggests that a LEEP-TH may have limited additional benefit over a single pass LEEP in the treatment of cervical HSIL.

Dysbiosis of Cervical and Vaginal Microbiota Associated With Cervical Intraepithelial Neoplasia.

Cervical intraepithelial neoplasia (CIN) is a precancerous condition inducing local lesions on the surface of the squamocolumnar junction of the cervix. Despite the role of vaginal microbiota having been under-discussed, the role of the cervical microbiome and the microbial migration across the reproductive tract involved in CIN was limitedly studied. We aimed to synchronously characterize the dysbiosis associated with CIN in both the cervix and vagina in a Chinese population. Profiling of cervical and vaginal microbiota from 60 CIN women and 60 healthy women was conducted. 16S rRNA sequencing was adopted. By comparing the microbial profiles between different parts of the reproductive tract, our results demonstrated an increased shift of microbial diversity in the cervix compared with that in the vagina for the CIN patients, specifically in CIN 1. Less dysbiosis was found between the CIN patients and controls, in either the vagina or cervix. The microbial community may be modulated by the onset of sexual activity, a known clinical risk factor for cervical neoplasia. Distinct patterns of perturbated bacteria were found in the vaginal and cervical microbiota, in which reduced Actinobacteria-related operational taxonomic units (OTUs) and increased Proteobacteria-related OTUs were found in the vagina and cervix, respectively. A good agreement between the direction of the top-significant perturbated OTUs was observed between the vaginal and cervical microbiome, suggesting a potential microbial migration in the reproductive tract. Enriched genera such as Sphingomonas and Stenotrophomonas were found in cervical microbiota-associated CIN. Multivariate analysis revealed Comamonas, Rhizobium, and Pseudomonas as independent genera contributing to CIN in the cervix. In summary, this study revealed the perturbation of microbiota in the presence of CIN and demonstrated a distinct pattern of characteristic bacteria community between the vagina and cervix involved in the development of CIN.

Association of a variant in the tumor necrosis factor alpha gene with risk of cervical cancer.

Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine involved in the regulation of the immune system and potentially the progression of cervical neoplastic lesions. In this study, we aimed to explore the possible relationship between polymorphisms of the TNF-α gene and susceptibility to cervical cancer. The relationship between a single nucleotide polymorphism (SNP) in the TNF-α gene (rs1800629) and the risk of cervical cancer was evaluated in a total of 445 subjects with (n = 153), or without (n = 292) cancer. Genotyping was performed using a Taq-Man based real time PCR method. Logistic regression analysis showed that individuals with AG/AA genotypes had an increased risk of cervical cancer compared to those with a GG genotype (OR 3.79, 95% CI 2.4-5.7, < 0.001). Our findings demonstrated that a genetic variant in the TNF-α gene (rs1800629) was associated with increased level and risk of developing cervical cancer, suggesting its potential use as a genetic risk factor for cervical neoplasia.

Association of a genetic variant in the angiopoietin-like protein 4 gene with cervical cancer

BackgroundCervical cancer is among the most aggressive gynecological tumors and is a consequence of interactions between genetic and epigenetic factors. Several genetic polymorphisms related to cervical cancer have been reported in previous clinical studies. In this study, we aimed to explore the possible relationship between polymorphisms of the ANGPTL4 gene locus and susceptibility to cervical cancer. MethodsWe investigated the relationship between a single nucleotide polymorphism (SNP) in the ANPGTL4 gene (rs116843064) and risk of cervical cancer in a total of 378 individuals with (n = 151), or without (n = 227) cancer. DNA was extracted, and genotyped using a Taq-Man based real time PCR. ResultsThe ANPGTL4 polymorphism was found to be associated with an increased risk of developing cervical neoplasia using dominant model (OR = 12.48, CI = 4.9−31.82, p < 0.0001) and additive model (OR = 30.54, CI = 7.35−126.89, p < 0.0001). ConclusionOur results indicate that there is a strong association between ANPGTL4 and the susceptibility for cervical cancer suggesting that it is a potential risk factor for cervical neoplasia.

The prevelance of human papillomavirus (HPV) genotypes detected by PCR in women with normal and abnormal cervico-vaginal cytology.

Cervical cancer is the second most common type of cancer for women worldwide with a great proportion proved to be related to human papillomavirus (HPV) infection. As infection with HPV is the strongest risk factor for cervical neoplasia, detection of HPV genotypes in cervical and vaginal specimens of women with normal and abnormal cytology seems to be of paramount importance in cervical cancer screening. The objective of the study is to evaluate the prevalence and HPV genotypes among women with normal or abnormal Pap smear tests. This retrospective study was conducted in a tertiary care university hospital in western Turkey. A total of 201 patients in whom both HPV typing and Pap test was performed between 2012 and 2016 in our obstetrics and gynecology department were enrolled in this study. Clinical and laboratory data were obtained for all participants. Cervical smears of the patients were classified by the Bethesda system and HPV analyses were done using the polymerase chain reaction (PCR) method. This study included 201 women, 72 of whom had normal and 129 of whom had abnormal Pap smear results. HPV DNA was detected in 91 (45.2%) of the 201 investigated women. Out of 72 patients with normal cervico-vaginal cytology, HPV positivity was detected in 35 (49%) patients, whereas 33 (35%) patients out of 94 with ASCUS , 18 (62%) patients out of 29 with LSIL and 5 (83%) patients out of 6 with HSIL had HPV positivity. Out of 35 HPV positive women that had normal pap test results, 25 (75%) were found to have high risk HPV (HR-HPV) genotypes. In women with ASCUS, LSIL and HSIL, HR-HPV genotype rates were found to be 94%, 89% and 100% respectively. The most common identified HPV types were HPV58, HPV16, HPV31, HPV33, HPV11 and HPV35. The frequency of HPV infection was found to be higher in our study compared to previous reports. Moreover, although HR-HPV genotypes were also detected in patients with normal cervical cytology, a majority of patients with HR-HPV genotypes were associated with abnormal cervical smear cytology including high rates of atypical squamous cells of undetermined significance, low-grade squamous intraepithelial lesion, and high-grade squamous intraepithelial lesion.

Cervical neoplasia in systemic lupus erythematosus: a nationwide study.

The aim was to examine the risk of cervical neoplasia in women with SLE, overall and with respect to treatment, compared with women from the general population. By linking national Swedish registers, we assembled a cohort including women with SLE (n = 4976) and matched general population comparators (n = 29 703). Two subcohorts of treated SLE patients were defined on the basis of treatment with antimalarials (n = 1942) and other immunosuppressants (AZA, CYC, ciclosporin, MTX, MMF or rituximab; n = 2175). The main outcome was defined as a first cervical neoplasia (dysplasia or cancer) during follow-up. Secondary outcomes were first cervical intraepithelial neoplasia (CIN) 1; first CIN grades 2-3; and first invasive cervical cancer during follow-up (2006-12). Cox regression models estimated relative risks adjusted for age, level of education, health-care utilization, number of children, marital status, family history of cervical cancer and prior cervical screening. Based on 121 events of cervical neoplasia during 23 136 person-years among SLE patients, there was an increased risk of any cervical neoplasia compared with the general population [hazard ratio (HR) = 2.12 (95% CI: 1.65, 2.71)]. The risk of CIN 1 [HR = 2.33 (95% CI: 1.58, 3.44)], CIN 2-3 [HR = 1.95 (95% CI: 1.43, 2.65)], but not invasive cervical cancer [HR = 1.64 (95% CI: 0.54, 5.02)], was increased in women with SLE. The subcohort treated with other immunosuppressants was at highest risk of cervical neoplasia. SLE is a risk factor for cervical neoplasia, in particular for pre-malignant cervical lesions. Among patients with SLE, the risk is higher among those treated with immunosuppresants compared with those treated with antimalarials.

Combined effect of diet and cervical microbiome on the risk of cervical intraepithelial neoplasia

Several food groups or dietary factors and the cervical microbiota may be involved in cervical carcinogenesis, but the evidence is not clear yet. We aimed to assess the association between dietary pattern and cervical intraepithelial neoplasia (CIN) and the combined effect of dietary pattern and cervical microbiome on the risk of CIN. The cervical microbiota and diet assessed by pyrosequencing and a food-frequency questionnaire, respectively, of 65 women with CIN and 72 control women were used in this study. Principal component analysis and cluster analysis were used to identify dietary patterns and microbiome community types, respectively. The association between dietary pattern and CIN risk was assessed using multivariable logistic regression analysis. The combined effect of dietary pattern and microbiome on CIN risk was determined using relative excess risk due to interaction (RERI) and synergy index (S). Two dietary patterns and four community types were identified: prudent diet characterized by higher intake of vegetables and fishes; semi-Western diet characterized by higher intake of bread, dairy products, eggs, and soft drinks and relatively higher fat intake ratio; and Lactobacillus crispatus-, L. iners-, Atopobium vaginae-, and Prevotella bivia-dominant types. The high-scoring group of participants with a semi-Western diet had a higher risk of CIN (odds ratio [OR] 3.44, 95% confidence interval [CI] 1.11-10.7, p=0.03), compared with the low or medium-scoring group of those with a semi-Western diet. L. iners-dominant (OR 6.39, 95% CI 1.52-26.7, p=0.01) and A. vaginae-dominant (OR 4.99, 95% CI 1.17-21.3, p=0.03) dominant types had a higher risk of CIN, compared with the L. crispatus-dominant type. The synergistic effect of semi-Western diet and A. vaginae-dominant type on CIN risk was observed (OR 20.8, 95% CI 2.21-195.6, p=0.01, RERI/S 9.64/1.96). Our findings suggest that semi-Western diet and its combination with A. vaginae-dominant microflora may represent an important risk factor for cervical neoplasia.

The association of uterine cervical microbiota with an increased risk for cervical intraepithelial neoplasia in Korea

Recent studies have suggested potential roles of the microbiome in cervicovaginal diseases. However, there has been no report on the cervical microbiome in cervical intraepithelial neoplasia (CIN). We aimed to identify the cervical microbiota of Korean women and assess the association between the cervical microbiota and CIN, and to determine the combined effect of the microbiota and human papillomavirus (HPV) on the risk of CIN. The cervical microbiota of 70 women with CIN and 50 control women was analysed using pyrosequencing based on the 16S rRNA gene. The associations between specific microbial patterns or abundance of specific microbiota and CIN risk were assessed using multivariate logistic regression, and the relative excess risk due to interaction (RERI) and the synergy index (S) were calculated. The phyla Firmicutes, Actinobacteria, Bacteroidetes, Proteobacteria, Tenericutes, Fusobacteria and TM7 were predominant in the microbiota and four distinct community types were observed in all women. A high score of the pattern characterized by predominance of Atopobium vaginae, Gardnerella vaginalis and Lactobacillus iners with a minority of Lactobacillus crispatus had a higher CIN risk (OR 5.80, 95% CI 1.73‒19.4) and abundance of A. vaginae had a higher CIN risk (OR 6.63, 95% CI 1.61‒27.2). The synergistic effect of a high score of this microbial pattern and oncogenic HPV was observed (OR 34.1, 95% CI 4.95‒284.5; RERI/S, 15.9/1.93). A predominance of A. vaginae, G. vaginalis and L. iners with a concomitant paucity of L. crispatus in the cervical microbiota was associated with CIN risk, suggesting that bacterial dysbiosis and its combination with oncogenic HPV may be a risk factor for cervical neoplasia.

Prevalence and risk factors for cervical neoplasia: a cervical cancer screening program in Beijing.

BackgroundCervical cancer is the second most common cancer and cause of cancer-related death for women worldwide. The aims of this study were to investigate the prevalence of cervical neoplasia and examine factors associated with high-grade cervical squamous intraepithelial lesions (HSIL) among women taking part in a cervical cancer screening program in Beijing.MethodsWomen aged 25–65 years were screened using the ThinPrep cytologic test and gynecologic examination. Univariate and multivariate logistic regressions were conducted to investigate factors associated with HSIL.ResultsAmong 728,704 women screened, the prevalence of cervical intraepithelial neoplasia (CIN) I, II, III was 50.2, 34.0, and 36.4 per 100,000, respectively. Prevalence of cervical cancer was 12.2 per 100,000. Risk factors for HSIL included being in age group of 46–55 years (adjusted odds ratio [aOR] = 1.15, 95% CI: 1.07–1.44, compared with the 25–35 age group), bleeding after intercourse (aOR = 2.08, 95% CI: 1.40–3.10), and presence of trichomonas vaginalis infection (aOR = 2.62, 95% CI: 1.35–5.07), cervical inflammation (aOR = 4.22, 95% CI: 3.39–5.26), and genital warts (aOR = 3.89, 95% CI: 2.54–7.70). High education level (college and above compared with junior middle school or lower) was found to be protective (aOR = 0.79, 95% CI: 0.37–0.90).ConclusionsThe prevalence of cervical neoplasia is relatively high in Beijing. Women aged 46–55 years, those with a lower education level, those reporting bleeding after intercourse, and those affected by Trichomonas vaginalis infection, cervical inflammation and genital warts are at higher risk for HSIL. Particular efforts should be made to ensure these women are included in cervical cancer screening programs.

Allelic Variations in CYP2D6 Gene and Susceptibility to Cervical Cancer

Epidemiological studies have identified a number of risk factors that contribute to the development of cervical cancer precursors and cervical cancer. These include infection with certain oncogenic types of human papillomaviruses (HPVs) and other socio-economic factors. Tobacco smoking is an independent risk-factor for cervical neoplasia. It has been found that polymorphism at loci that encode carcinogen-metabolizing enzyme such as cytochrome P450 2D6 (CYP2D6) catalyzing the detoxification of carcinogens may determine susceptibility to cervical cancer. Therefore, it is likely that an understanding of these allelic differences is important for determining an individual's risk of cancer and susceptibility to potentially toxic agents. The aim of the present study was to elucidate the role of CYP2D6 polymorphism and susceptibility to squamous cell carcinoma of the uterine cervix in Indian population. Therefore, the genotype frequencies at this locus in females suffering with low-grade CIN, high-grade CIN and squamous cell carcinoma were compared. The control group consisted of 77 females with normal cervical cytology and the cases comprised of 61 mild/moderate dysplasia, 48 severe dysplasia and 45 cases of squamous cell carcinoma of uterine cervix. The individuals were divided into poor metabolizers (PM) and extensive metabolizers (EM) on the basis of their ability to metabolize certain drugs and carcinogens. Comparison of the frequency distribution for the combination of CYP2D6 EM genotype and smoking between mild/moderate and severe dysplasia was statistically significant (p=0.047) suggesting that women with cervical intraepithelial neoplasia I/II (CIN I/ CIN II) and CYP2D6 EM genotype who smoke appears to have more chances for the lesions to progress to CIN III. Whereas, frequency distribution for the same combination between severe dysplasia and squamous cell carcinoma failed to attain any statistical significance suggesting that CIN III with CYP2D6 EM genotype has less chance to progress to cervical cancer. Increased frequency of CYP2D6 EM and tobacco smoking show strong association with CIN III, indicating that not all lesions with the histopathological high grade CIN are premalignant. Conversely some squamous cell carcinomas may not be preceded by CIN.

Ist die frühe Kohabitarche ein Risikofaktor des Zervixkarzinoms?

Seit vielen Jahrzehnten gilt das Sexualverhalten als Risikofaktor des Zervixkarzinoms. Alle damit assoziierten Faktoren sind nur bei chronischer Infektion der zervikalen Transformationszone mit humanen Papillomaviren (HPV) des Hochrisikotyps von Relevanz. Mehrere retrospektive Analysen machen eine frühe Kohabitarche als krankheitsfördernden Umstand für das spätere Auftreten eines Zervixkarzinoms wahrscheinlich. Da verschiedene Risikofaktoren miteinander zusammenhängen können, ist die Frage nach dem Einzelbeitrag einer frühen Kohabitarche zur Entstehung des Zervixkarzinoms umstritten. Umsichtig geplante prospektive Studien fehlen zu diesem Thema. Vieles spricht dafür, dass die zervikale Transformation zwischen der Menarche und etwa dem 16. Lebensjahr besonders vulnerabel für HPV ist. In diesem Alter liegen während der Metaplasie eine grosse Anzahl sich umdifferenzierender Zellen an der Oberfläche der Zervix. Dies begünstigt offensichtlich stark das Angehen einer HPV-Infektion. Auch gibt es Hinweise, dass bei früher Kohabitarche oft noch keine sekundäre Immunantwort gegen HPV besteht. Dies macht die Immunantwort gegen das Virus weniger effizient. Neben einer genetischen Prädisposition sind weiterhin verschiedene Variablen des täglichen Lebens wie einseitige Ernährung, Rauchen, Entzündungen mit Chlamydien oder HSV-2, langjährige orale Kontrazeption, Drogenabusus, Immunsuppression und frühe erste Schwangerschaft als HPV-assoziierte Kofaktoren der zervikalen Karzinogenese von Bedeutung. Eine adäquate Aufklärung junger Menschen sollte deren İberzeugung fördern, dass sie aktive Gestalter ihres eigenen Lebens sind, was neben der Akzeptanz ihres sexuell reifen Körpers wesentlich auch Verantwortlichkeit im Freiraum der eigenen Lebensgestaltung bedeutet.

Active and Passive Cigarette Smoking and the Risk of Cervical Neoplasia

Evidence links active cigarette smoking to cervical neoplasia, but much less is known about the role of passive smoking. Using a prospective cohort design, we examined personal cigarette smoking and household passive smoke exposure in relation to the risk of cervical neoplasia. Cohorts were established based on data collected on the smoking status of all household members during private censuses of Washington County, Maryland in 1963 (n = 24,792) and 1975 (n = 26,381). Using the Washington County Cancer Registry, the occurrence of cervical neoplasia in the two cohorts was ascertained from 1963-1978 and from 1975-1994. Poisson regression models were fitted to estimate the relative risk of developing cervical neoplasia associated with active and passive smoking in both cohorts. The referent category for all comparisons was never smokers not exposed to passive smoking. The adjusted relative risk and 95% confidence limits for passive smoking was 2.1 (1.3, 3.3) in the 1963 cohort and 1.4 (0.8, 2.4) in the 1975 cohort. The adjusted relative risk and 95% confidence limits for current smoking were 2.6 (1.7, 4.1) and 1.7 (1.1, 2.6) in the 1963 and 1975 cohort, respectively. The associations were in the direction of increased risk for both passive smoking and current active smoking in both the 1963 and 1975 cohorts, but were stronger in the 1963 cohort. The results of this long-term, prospective cohort study corroborate the association between active cigarette smoking and cervical neoplasia and provide evidence that passive smoking is a risk factor for cervical neoplasia.

Burning wood in the kitchen increases the risk of cervical neoplasia in HPV-infected women in Honduras.

There is suggestive evidence that the use of wood for cooking increases the risk of invasive cervical cancer. We investigated this association in women with cervical neoplasia in Honduras. Women aged 20-64 years with cervical intraepithelial neoplasia (CIN) grade I (n = 44), CIN II (n = 36) or CIN III (n = 45) were recruited from screening programs in Tegucigalpa City and each was matched by age and clinic to 2 controls (241 total) without cervical abnormalities. The clinics selected women of low socioeconomic status. Cervical scrapes were tested for the presence of human papillomavirus (HPV) DNA using a general primer set directed against the L1 open reading frame, and HPV genotyping was performed. Odds ratios (ORs) were computed through conditional logistic regression; p-values were from tests for linear trend of risk with increasing exposure. HPV DNA was detected in 48% of women with CIN I, 67% with CIN II and 89% with CIN III. The ORs were 1.5, 2.5 and 38.3 respectively. At univariate analysis, age at first intercourse was consistently lower among cases than controls. Risk was reduced by 50% or more in all 3 CIN classes when initiation of sexual activity at age 20 years or older was compared with initiation before age 16 years (p = 0.013 for CIN I). No effect was observed for smoking, oral contraceptives or previous cytologic screening. Effects for number of sexual partners, parity, age at first pregnancy and education were in the expected directions but never persisted after adjustment for HPV. Chronic exposure to wood smoke significantly increased the risk of CIN III (p = 0.022). However, women who said "No" when asked if they ever used wood in the kitchen had a higher risk than those with low or intermediate exposure. This was taken as evidence that the initial screening question had either been misunderstood or that answers were biased. Restricting the analysis to women who reported exposure yielded positive associations in all CIN classes with for CIN III ORs of 2.3 for 25-34 and 9.5 for 35+ years compared with women who had 1-14 years of exposure (p = 0.017). A multivariate analysis of the complete dataset (n = 366) allowed for separate ORs for HPV in each CIN class. Inclusion of age at first intercourse significantly improved this model (p = 0.021). Adding exposure to wood smoke further improved the model only if an interaction between woodsmoke and HPV was allowed for. If, as the data suggest, it was assumed that wood smoke had its effect among HPV-positives only, there was a significant linear dose-response relationship between exposure to woodsmoke and risk of CIN (p = 0.026). This association was independent of other risk factors including education, parity and number of sexual partners. ORs in the final model were 0.37 for age at first intercourse 20 years or higher and 5.69 for more than 35 years of exposure to wood burning in the kitchen. The present study suggests that the use of wood for cooking is a risk factor for cervical neoplasia that deserves further study, given its high prevalence in developing countries.

Cervical neoplasia risk in women provided hormonal contraception without a Pap smear

The study was conducted to determine whether women using a demonstration program providing hormonal birth control without concurrent pelvic examination ( First Stop) are at higher risk of cervical neoplasia compared to women using traditional family planning clinics. Using retrospective ion of medical charts, we compared risk factors for cervical neoplasia among 400 First Stop clients and 400 traditional site clients matched on age, race, and contraceptive method. We determined prevalence of these factors: previous abnormal cervical smear, <16 years at first intercourse, multiple sexual partners, high parity, history of sexually transmitted infections, and current cigarette smoking. First Stop clients were not at greater likelihood of having any risk factor for cervical neoplasia except high parity. First Stop clients who failed to follow through on a referral to a traditional clinic were not more likely to be of higher risk than those who did follow through. Of 13 First Stop clients with the highest risk profiles (previous abnormal cervical smear plus one other risk factor), one did not follow through with referral. First Stop clients choosing hormonal contraception without a pelvic examination do not appear to be at substantially higher risk of cervical neoplasia. Future research should quantify more precisely the risks and benefits of the general application of this strategy on a population level.

Selective screening for cervical neoplasia: an approach for resource-poor settings.

Cervical malignancies are the leading cause of cancer-related morbidity and mortality among women in developing countries. Although early detection programmes using cytological methods, followed by aggressive treatment of precursor lesions are accepted as the main disease control strategy, fiscal limitations make this strategy unfeasible in many countries. To screen selectively, we developed two risk scores using data from a population-based case-control study in Jamaica with 202 cases and 363 controls. Independent risk factors for cervical neoplasia were determined using logistic regression. An unweighted risk score for each subject was developed by a simple count of risk factors present and a weighted risk score was calculated by summing regression coefficients for each risk factor. Four patient characteristics were independently predictive of cervical neoplasia, older age (OR = 3.4, 95% CI : 1.8-6.7), > or = 4 pregnancies (OR = 5.6, 95% CI : 1.2-18.7), poverty (OR = 2.1, 95% CI : 1.3-3.3) and cigarette smoking (OR = 1.9, 95% CI : 1.2-3.2). Using cut-off points of > or = 20 for the weighted scores and > 3 for unweighted scores, the sensitivity and specificity were 65% and 69% for the unweighted score and 75% and 61%, respectively, for the weighted score. Areas under the receiver operating characteristic (ROC) curves for the weighted versus the unweighted scores were similar, suggesting similar overall accuracy. Selective screening using risk assessment strategies is potentially useful, particularly in resource-poor settings. However, whether weighting factors is essential is dependent on prevalence of factors in a given setting. Although this approach needs validation in other populations, women at highest risk for cervical neoplasia can be identified using demographic factors available during a regular clinic visit.

Smoking, diet, pregnancy and oral contraceptive use as risk factors for cervical intra-epithelial neoplasia in relation to human papillomavirus infection.

Smoking, nutrition, parity and oral contraceptive use have been reported as major environmental risk factors for cervical cancer. After the discovery of the very strong link between human papillomavirus (HPV) infection and cervical cancer, it is unclear whether the association of these environmental factors with cervical cancer reflect secondary associations attributable to confounding by HPV, if they are independent risk factors or whether they may act as cofactors to HPV infection in cervical carcinogenesis. To investigate this issue, we performed a population-based case–control study in the Västerbotten county of Northern Sweden of 137 women with high-grade cervical intra-epithelial neoplasia (CIN 2–3) and 253 healthy age-matched women. The women answered a 94-item questionnaire on diet, smoking, oral contraceptive use and sexual history and donated specimens for diagnosis of present HPV infection (nested polymerase chain reaction on cervical brush samples) and for past or present HPV infections (HPV seropositivity). The previously described protective effects of dietary micronutrients were not detected. Pregnancy appeared to be a risk factor in the multivariate analysis (P< 0.0001). Prolonged oral contraceptive use and sexual history were associated with CIN 2–3 in univariate analysis, but these associations lost significance after taking HPV into account. Smoking was associated with CIN 2–3 (odds ratio (OR) 2.6, 95% confidence interval (CI) 1.7–4.0), the effect was dose-dependent (P = 0.002) and the smoking-associated risk was not affected by adjusting for HPV, neither when adjusting for HPV DNA (OR 2.5, CI 1.3–4.9) nor when adjusting for HPV seropositivity (OR 3.0, CI 1.9–4.7). In conclusion, after taking HPV into account, smoking appeared to be the most significant environmental risk factor for cervical neoplasia. © 2000 Cancer Research Campaign

Attack rates of human papillomavirus type 16 and cervical neoplasia in primiparous women and field trial designs for HPV16 vaccination

Background: Identification of human papillomavirus type 16 (HPV16) as the major risk factor for cervical neoplasia, and mass production of DNA free HPV capsids have paved the way to preventive...

HIV and human papillomavirus as independent risk factors for cervical neoplasia in women with high or low numbers of sex partners.

OBJECTIVE: To explore whether HIV types 1 and 2 and CD4 cell count affect cervical neoplasia independent of human papillomavirus (HPV) in women with high or low numbers of sexual...

Risk factors for cervical neoplasia in Denmark

With the overall goal of elucidating the risk factor pattern for cervical neoplasia, two case-control studies and a prospective cohort study were conducted. The first case-control study focused on female lifestyle risk factors. It was designed to include all women (aged 20-49 years) in Greater Copenhagen, diagnosed with invasive cervical cancer or carcinoma in situ (CIS) from January 1985 to December 1986. They were identified from the Danish Cancer Registry. An age-stratified control group was randomly selected from the study area by means of The Danish Central Population Register. Information on risk factors was collected using a self-administered questionnaire. The study, which included 586 women with CIS, 59 women with cervical cancer, and 614 control subjects, confirmed that CIS and invasive cervical cancer share similar risk factors. Both disease entities were strongly associated with sexual and venereal factors. This applied especially to lifetime number of sexual partners and age at first episode with genital warts (proxy measure for human papillomavirus (HPV)), supporting that HPV infection in the adolescent cervix is associated with a higher risk of cervical neoplasia compared with such an infection later in life. Our results also suggested that parity, oral contraceptive use, and smoking may be important risk factors. In the second case-control study, we identified all women with one lifetime sexual partner based on the questionnaire information obtained in the first case-control study. To investigate the role of the "male factor", the women were invited to participate in the study together with their husband. In all, 41 case couples and 90 control couples were enrolled. Data collection included a personal interview, blood samples, and penile swabs from the males. The most significant risk determinants of cervical neoplasia were a history of genital warts in the male and non-use of condoms, emphasizing the venereal nature and pointing to HPV as an important agent. Genital warts are usually associated with the low-risk HPVs (types 6 and 11) rather than with the high-risk HPV types. However, an explanation for the observed relationship between risk of cervical neoplasia and genital warts in the woman herself and in her male partner could be, that they are more likely also to harbour the high-risk HPV types. Only 2 case husbands and no control husbands had HPV DNA detected in the penile swabs (ViraPapR, ViraTypeTM). As the number of cells in the swab always exceeded 3 x 10(4), the result may reflect shortcomings in the test kit used. From our population-based prospective cohort study of 11,088 women, we selected the prevalent cases (199 women with LSIL/HSIL(low-grade/high-grade squamous intraepithelial neoplasia), 131 women with ASCUS (atypical squamous cells of undetermined significance)), and 1000 random controls (women and normal cervical cytology). At enrollment, the women were personally interviewed and had a gynecological examination including cervical swabs for HPV testing and a Pap smear. HPV DNA detection was done using polymerase-chain-reaction methods. Cervical HPV infection (especially with the high-risk types) was the out-standing risk factor for all grades of neoplasia, the association being strongest for HSIL. Women with high-risk HPV infection had a nearly 33-fold increased risk of HSIL compared to HPV-negative women. Possible risk factors for cervical neoplasia in HPV-positive women included smoking, non-use of barrier contraceptives and parity. If analysis was restricted to histologically confirmed high-grade lesions, the proportion of cases that could be attributed to HPV infections was 80%. The importance and urgent need for studies which include HPV as an adjunct to cervical cytology is emphasized. Greater effort should be made to determine the usefulness of this modality (HPV diagnostics) in cervical cancer screening or in the management of cervical neoplasia, especially ASCUS and LSIL.

History of genital warts in 10,838 women 20 to 29 years of age from the general population. Risk factors and association with Papanicolaou smear history.

The most important risk factor for cervical neoplasia is genital infection with certain types of human papillomavirus (HPV). Genital warts (GW) are an easily recognizable condition caused by HPV. Although only a fraction of HPV infections are clinical, a history of ever having had GW could serve as a marker for exposure to HPV. To study the risk factors for ever having had GW. The association of GW with abnormal Papanicolaou (Pap) smear and relation to cervical neoplasia is also discussed. A case-control study among 10,838 women aged 20 to 29 years and reporting at least one lifetime sexual partner. The women were participants in a prospective cohort study on the relationship between HPV and cervical neoplasia in Copenhagen, Denmark. Data were obtained by means of personal interviews using structured questionnaires. In all, 1,820 women (17%) reported ever having had GW. The most important risk factor was the number of lifetime of sexual partners (adjusted odds ratio 5.2; 95% confidence interval: 3.4-8.0) for at least 40 partners vs. 1 to 2 partners). The number of regular partners, sexually active years, a history of chlamydial infection, and smoking were also associated with the risk of ever having had GW. Women who had had GW were 1.9 times more likely than other women to report an abnormal Pap smear. The study confirms the sexual transmission of the infection. There is also good concordance between risk factors for ever having had GW and cervical neoplasia. A close relationship between having had GW and an abnormal Pap smear was observed.