Relative Risk Of Cervical Cancer Research Articles

The detection of high risk HPV genotypes by the PR-PCR method in the Republic of Serbia

Abstract Introduction The association between Human Papiloma Virus (HPV) positive cervical swabs and the development of cervical cancer has lead to extensive research. Studies employing the RT-PCR method for typization in the young women demographic worldwide. Based on their proven oncogenic potential 14 HPV types have been classified as carcinogenic (HPV16,18,31,33,35,39,45,51,52,56, 58,59,66,68). The imporatnce of HPV diagnostics is a result of the existing link between viral infection and relative risk of cervical cancer, while the detection complexity reflects the large variety of HPV genotypes. Methods The samples analyzed in our study were obtained from cervical swabs of women aged 19 to 25 years between the months of October and December 2022. All collected samples were routinely screened for high risk genotype positivity (HPV16 and 18). There were no other inclusion criteria, the samples used in the study were selected at random. After DNA isolation, genotype identification was done by L2 amplification for HPV 16, the L1 for HPV 18, E6 for HPV 35, 56 and 58, and E7 for HPV 31,33,39,45,51,52,59,66 and 68 genotypes, with specific primers and flourescently labelled probes. Results The results demonstrated that among the DNA positive individuals HPV genotype distribution was as follows: 50% (31,39,56); 40,90% HPV(52,59,68); 34,10% HPV16; 22,70% HPV(35, 58, 66); 15,90% HPV 18. Individually, by type, the highest prevalence was noted for the high risk genotype HPV 16 (34,1%), followed by HPV18 (15,90%). As for group clusters, HPV(31,39,56) were most frequent, followed by HPV(52,59,68). Conclusions Given the forementioned results of our study, the most prevalent HPV genotype in the Republic of Serbia among the women of pre-set demographic is HPV 16, which is in conconcurrence with epidemiological results for Eastern Europe. By comparative analysis of the HPV16 and 31 distribution, the results imply a similarity in sensitivity to infection. Key messages • The susceptibility of young adults to HPV infection entails a well-developed preventive medicine program is paramount, and not limited to this demographic. • RT-PCR offers in-depth insight into the distribution of risk of cancer to the screening team.

Dose-risk relationships between cigarette smoking and cervical cancer: a systematic review and meta-analysis.

Cervical cancer (CC) is the fourth most frequent cancer worldwide. Cigarette smoking has been shown to influence CC risk in conjunction with human papillomavirus (HPV) infection. The aim of this study is to provide the most accurate and updated estimate of this association and its dose-response relationship. Using an innovative approach for the identification of original publications, we conducted a systematic review and meta-analysis of studies published up to January 2021. Random effects models were used to provide pooled relative risks (RRs) of CC for smoking status. Dose-response relationships were evaluated using one-stage random effects models with linear or restricted cubic splines models. We included 109 studies providing a pooled RR of invasive CC and preinvasive lesions, respectively, of 1.70 [95% confidence interval (CI), 1.53-1.88] and 2.11 (95% CI, 1.85-2.39) for current versus never smokers, and, respectively, 1.13 (95% CI, 1.02-1.24) and 1.29 (95% CI, 1.15-1.46) for former versus never smokers. Considering HPV does not alter the positive association or its magnitude. Risks of CC sharply increased with few cigarettes (for 10 cigarettes/day, RR = 1.72; 95% CI, 1.34-2.20 for invasive CC and RR = 2.13; 95% CI, 1.86-2.44 for precancerous lesions). The risk of CC increased with pack-years and smoking duration and decreased linearly with time since quitting, reaching that of never smokers about 15 years after quitting. This comprehensive review and meta-analysis confirmed the association of smoking with CC, independently from HPV infection. Such association rose sharply with smoking intensity and decreased after smoking cessation.

The effects of the national HPV vaccination programme in England, UK, on cervical cancer and grade 3 cervical intraepithelial neoplasia incidence: a register-based observational study

Human papillomavirus (HPV) immunisation with a bivalent vaccine (Cervarix) was introduced in England, UK, in Sept 1, 2008: routine vaccination was offered to girls aged 12-13 years with a catch-up programme for females aged 14-18 years in 2008-10. We quantified the early effect of this immunisation programme on cervical cancer and cervical carcinoma in situ, namely grade 3 cervical intraepithelial neoplasia (CIN3), registrations. In this observational study, we used an extension of the age-period-cohort Poisson model to estimate the relative risk of cervical cancer in three vaccinated cohorts compared with earlier cohorts that were not eligible for HPV vaccination. Data from a population-based cancer registry were extracted on Jan 26, 2021, and were assessed for diagnoses of cervical cancer and CIN3 from Jan 1, 2006 to June 30, 2019 in women aged 20-64 years and who were a resident in England. We used three vaccinated cohorts to account for differences in the school year in which the vaccine was offered and its national coverage. Adjustment for confounding was made using information on changes in cervical screening policy and historical events that affected cervical cancer incidence. Results were compared across models with different adjustments for confounders. We used data from a total of 13·7 million-years of follow-up of women aged 20 years to younger than 30 years. The estimated relative reduction in cervical cancer rates by age at vaccine offer were 34% (95% CI 25-41) for age 16-18 years (school year 12-13), 62% (52-71) for age 14-16 years (school year 10-11), and 87% (72-94) for age 12-13 years (school year 8), compared with the reference unvaccinated cohort. The corresponding risk reductions for CIN3 were 39% (95% CI 36-41) for those offered at age 16-18 years, 75% (72-77) for age 14-16 years, and 97% (96-98) for age 12-13 years. These results remained similar across models. We estimated that by June 30, 2019 there had been 448 (339-556) fewer than expected cervical cancers and 17 235 (15 919-18 552) fewer than expected cases of CIN3 in vaccinated cohorts in England. We observed a substantial reduction in cervical cancer and incidence of CIN3 in young women after the introduction of the HPV immunisation programme in England, especially in individuals who were offered the vaccine at age 12-13 years. The HPV immunisation programme has successfully almost eliminated cervical cancer in women born since Sept 1, 1995. Cancer Research UK.

Cervical cancer case-control audit: Results from routine evaluation of a nationwide cervical screening program.

Our study used a refined case–control cervical cancer Audit framework to investigate effectiveness of cervical screening, with measures of three screening failures: irregular‐participation, cervical cancer developed after cytological abnormalities and after normal screening results. The register‐based study included 4,254 cervical cancer cases diagnosed in Sweden during 2002–2011, and 30 population‐based controls per case. We used conditional logistic regression models to examine relative risks of cervical cancer in relation to screening participation and screening results in the past two screening rounds from 6 months before cancer diagnosis. We found that women unscreened in past two screening rounds showed four times increased risk of cervical cancer compared to women screened in time (OR = 4.1, 95% CI = 3.8–4.5), and women unscreened in the previous round but screened in the most recent round also showed a statistically significantly elevated risk (OR = 1.6, 95% CI = 1.5–1.8). Women having abnormality in previous two rounds exhibited higher risk of cervical cancer compared to women screened with normal results, while having normal results in the subsequent round after the abnormality also yielded an increased risk (OR = 4.0, 95% CI = 3.2–5.1). Being screened with only normal results was associated with 89% risk reduction for squamous cell cancer, compared to women unscreened, but only 60% reduction for adenocarcinoma. Our findings emphasize the importance of routine participation in cervical screening and suggest that management of abnormalities, as well as sensitivity of the test, warrants improvement especially for preventing cervical adenocarcinoma. The Audit framework serves as routine evaluation model and the findings benchmark for future evaluation of changes in screening practice.

Prevalence of human papillomavirus genotypes and relative risk of cervical cancer in China: a systematic review and meta-analysis.

High-risk HPV (hrHPV) is related to cervical carcinogenesis, although clinical data comparing the natural history and carcinogenic potential of type-specific HPV remain limited. Furthermore, the nationwide prevalence rates of overall and type-specific HPV among women with cervical precancerous lesions and cancer have not been reported. Here, a meta-analysis was performed for type-specific HPV distribution among 30,165 HPV-positive women, including 12,094 invasive cervical cancers (ICCs), 10,026 cervical intraepithelial neoplasia grade 2/3 (CIN2/3), 3246 CIN1, and 4799 normal cervices from 45 PCR-based studies. We found that HPV16 was the most common hrHPV type involved in cervical disease. The HPV16 positivity rate varied little across normal (22.7%) and CIN1 individuals (23.6%) but increased through the CIN2 (37.6%) and CIN3 patients (51.9%) to 65.6% in ICC cases. HPV16, 18, 35, 39, 45, and 59 were more frequent in ICC than CIN3, with ICC:CIN3 ratios ranging from 2.3 for HPV18 to 1.1 for HPV35/45. HPV31, 33, 52, and 58 were more frequent in CIN3 compared with normal cervices but less common in ICC compared with CIN3 (ICC:CIN3 ratios ranging from 0.6 for HPV58 and 0.4 for HPV52). The ICC:normal ratios were particularly high for HPV18, 52 and 58 in West China (4.1, 3.9 and 2.9, respectively) and for HPV45 and 59 in North China (1.6 and 1.1, respectively). In summary, this study is the most comprehensive analysis of type-specific HPV distribution in cervical carcinogenesis and could be valuable for HPV-based cervical cancer screening strategies and vaccination policies in China.

Long-term risk of cervical cancer following conization of cervical intraepithelial neoplasia grade 3-A Danish nationwide cohort study.

Using nationwide Danish registries we examined the long-term risk of cervical cancer in women diagnosed with cervical intraepithelial neoplasia grade 3 (CIN3) (including adenocarcinoma in situ (AIS)) on the cone compared to women with a normal cytology test. Initially, we identified women born 1918-1990, who were recorded as living in Denmark between January 1, 1978 and December 31, 2012. From the Pathology Data Bank information on CIN3 on the cone, margins status, histological type of CIN3 and cervical cytology results was extracted. Cox proportional hazard model was used to estimate the relative risk of subsequent cervical cancer. We included 59,464 women with CIN3 on the cone and 1,918,508 women with a normal cytology test. Overall, women diagnosed with CIN3 had a higher risk of subsequent cervical cancer compared to women with normal cytology (HR = 2.06; 95%CI: 1.81-2.35). Analyses according to time since conization showed elevated risks in all time periods, and 25 years or more after conization the relative risk was significantly increased (HR = 2.56; 95%CI: 1.37-4.77). Twenty years or more after conization, also women with negative margins had an increased relative risk (HR = 2.49; 95%CI: 1.12-5.57). In addition, the long-term relative risk of cervical cancer varied with the different histological types of CIN3 and was highest for AIS (HR = 7.50; 95%CI: 1.87-30.01, 10-14 years after conization). In conclusion, women diagnosed with CIN3 on the cone have a long-lasting increased risk of cervical cancer even when the margins on the cone are negative.

Cervical cancer incidence in young women: a historical and geographic controlled UK regional population study

Background:The commencing age of cervical screening in England was raised from 20 to 25 years in 2004. Cervical cancer incidence in young women of England is increasing. It is not clear if this is due to either greater exposure to population risk factors or reduced cervical screening.Methods:We measured if the relative risk of cervical cancer in younger women (20–29 years) of the north-east of England (NE) differed to that of women aged 30yrs and above since 2004. We also measured average annual percentage change (AAPC) in the 3 yr moving average incidence for all age-groups. Regional screening coverage rate and population risk factors were reviewed. Comparisons were made with Wales where screening continues to commence from the age of 20 yrs.Results:Cervical cancer incidence in women aged 20–29 increased annually by an average of 10.3% between 2000 and 2009. The rise in women aged 30–39 was less steep (3.5%/year) but no significant rise was observed in women aged 40–49. Socioeconomic factors remained stable or improved during the time period except for the incidence of chlamydia, herpes simplex and in particular, genital warts, which increased significantly in young women. Data from Wales show similar results.Conclusion:The incidence of cervical cancers in young women of the NE is increasing. The rise in incidence is unrelated to the change in screening policy in 2004. Close monitoring of incidence in young women and a greater attempt to reverse the current decline in screening coverage of women aged 25–29 years are recommended.

Relative risk of cervical cancer in indigenous women in Australia, Canada, New Zealand, and the United States: A systematic review and meta-analysis

We performed a systematic review and meta-analysis of cervical cancer risk in indigenous women in Australia, Canada, New Zealand, and the United States, in order to identify whether risks of cervical dysplasia, cervical cancer, and cervical cancer-related mortality are higher in indigenous relative to non-indigenous populations. We identified 35 studies published in 1969-2008. In our findings, indigenous populations did not have an elevated risk of cervical dysplasia or carcinoma in situ relative to non-indigenous populations, but had elevated risks of invasive cervical cancer (pooled RR=1.72) and cervical cancer-related mortality (pooled RR=3.45). There was a log-linear relationship between relative risk and disease stage. In conclusion, the indigenous women have a markedly higher risk of cervical cancer morbidity and mortality than non-indigenous women, but no increased risk of early-stage disease, suggesting that structural, social, or individual barriers to screening, rather than baseline risk factors, are influencing poor health outcomes.

Risk of cervical cancer among immigrants by age at immigration and follow‐up time in Sweden, from 1968 to 2004

Because of great variation in the prevalence of human papilloma virus infection and other risk factors of cervical cancer worldwide, migrant studies may help further the understanding of the aetiology and improve prevention of cervical cancer. Our aim was to study the risk of invasive cervical cancer among immigrant women. We followed 758,002 immigrants from different countries who resided in Sweden between 1968 and 2004. Age-standardised incidence rates (ASRs) of immigrants were compared with that in their countries of origin. Poisson regression models estimated the relative risks of cervical cancer among immigrants, overall and stratified by age at migration and follow-up time, compared to Swedish-born women. Overall 1,991 of 19,542 observed cases of cervical cancer occurred among immigrants. Generally they had lower ASRs than in their countries of origin, with the exception of Nordic immigrants. Compared to Swedish-born women, we observed a higher relative risk of cervical cancer among immigrants overall (RR = 1.13, 95% CI 1.08-1.18), and particularly among women from Denmark (RR = 1.8, 95% CI 1.6-2.1), Norway (RR = 1.7, 95% CI 1.5-1.9) and Central America (RR = 2.5, 95% CI 1.3-4.9), while the relative risks were lower in immigrants from Eastern Africa (RR = 0.2, 95% CI 0.1-0.6), South Central Asia (RR = 0.4, 95% CI 0.2-0.6) and South Western Asia (RR = 0.5, 95% CI 0.4-0.7). Follow-up time and age at migration were important effect modifiers for cervical cancer risks. We suggest targeted prevention toward high-risk immigrants, specifically older women, in the first 10 years after arrival into their new homeland.

Cervical cancer and hormonal contraceptives: collaborative reanalysis of individual data for 16 573 women with cervical cancer and 35 509 women without cervical cancer from 24 epidemiological studies

Combined oral contraceptives are classified by the International Agency for Research on Cancer as a cause of cervical cancer. As the incidence of cervical cancer increases with age, the public-health implications of this association depend largely on the persistence of effects long after use of oral contraceptives has ceased. Information from 24 studies worldwide is pooled here to investigate the association between cervical carcinoma and pattern of oral contraceptive use. Individual data for 16,573 women with cervical cancer and 35,509 without cervical cancer were reanalysed centrally. Relative risks of cervical cancer were estimated by conditional logistic regression, stratifying by study, age, number of sexual partners, age at first intercourse, parity, smoking, and screening. Among current users of oral contraceptives the risk of invasive cervical cancer increased with increasing duration of use (relative risk for 5 or more years' use versus never use, 1.90 [95% CI 1.69-2.13]). The risk declined after use ceased, and by 10 or more years had returned to that of never users. A similar pattern of risk was seen both for invasive and in-situ cancer, and in women who tested positive for high-risk human papillomavirus. Relative risk did not vary substantially between women with different characteristics. The relative risk of cervical cancer is increased in current users of oral contraceptives and declines after use ceases. 10 years' use of oral contraceptives from around age 20 to 30 years is estimated to increase the cumulative incidence of invasive cervical cancer by age 50 from 7.3 to 8.3 per 1000 in less developed countries and from 3.8 to 4.5 per 1000 in more developed countries.

Relative Risk of Cervical Cancer Rises with Duration of Oral Contraceptive Use

The relative risk of cervical cancer rises the longer a woman is on the pill. According to a meta-analysis based on data from 28 studies women who use the pill for 10 or more years are 2.2 times as likely as never-users to develop cervical cancer whereas the relative risks among users for 5-9 years and fewer than five years are 1.6 and 1.1 respectively. Among women infected with human papillomavirus (HPV) the virus associated with virtually all cases of cervical cancer long-term pill users are 2.5 times as likely as never-users to develop cervical cancer. The results were broadly similar among the studies despite the wide variation in the individual variables that were statistically controlled for. (excerpt)

The epidemiology of cervical cancer.

Cervical cancer is one of the most common neoplastic diseases affecting women, with a combined worldwide incidence of almost half a million new cases annually, second only to breast cancer. Basic and epidemiologic research conducted during the past 15-20 years have provided overwhelming evidence for an etiologic role for infection with certain types of sexually-transmitted human papillomavirus (HPV) as the primary cause of cervical cancer. The relative risks of cervical cancer following HPV infection as ascertained in case-control and cohort studies are among the highest in cancer epidemiology. The available evidence indicates that the HPV-cervical cancer association satisfies all relevant causal criteria for public health action. Other cervical cancer risk factors, such as smoking, parity, use of oral contraceptives, diet, other infections, and host susceptibility traits must be understood in the context of mediation of acquisition of HPV infection or in influencing events of the natural history of cervical neoplasia that occur following the establishment of a persistent HPV infection. Virtually all cervical carcinoma specimens contain HPV DNA, which suggests that HPV infection is a necessary cause of cervical neoplasia. This is the first instance in which a necessary cause has been demonstrated in cancer epidemiology--a realization that has obvious implications for primary and secondary prevention of this neoplastic disease.

Cervical cancer and use of hormonal contraceptives: a systematic review

Human papillomavirus (HPV) is believed to be the most important cause of cervical cancer. Recent studies suggest that long duration use of oral contraceptives increases the risk of cervical cancer in HPV positive women. Results from published studies were combined to examine the relationship between invasive and in situ cervical cancer and duration and recency of use of hormonal contraceptives, with particular attention to HPV infection. 28 eligible studies were identified, together including 12531 women with cervical cancer. Compared with never users of oral contraceptives, the relative risks of cervical cancer increased with increasing duration of use: for durations of approximately less than 5 years, 5-9 years, and 10 or more years, respectively, the summary relative risks were 1.1 (95% CI 1.1-1.2), 1.6 (1.4-1.7), and 2.2 (1.9-2.4) for all women; and 0.9 (0.7-1.2), 1.3 (1.0-1.9), and 2.5 (1.6-3.9) for HPV positive women. The results were broadly similar for invasive and in situ cervical cancers, for squamous cell and adenocarcinoma, and in studies that adjusted for HPV status, number of sexual partners, cervical screening, smoking, or use of barrier contraceptives. The limited available data suggest that the relative risk of cervical cancer may decrease after use of oral contraceptives ceases. However, study designs varied and there was some heterogeneity between study results. Although long duration use of hormonal contraceptives is associated with an increased risk of cervical cancer, the public health implications of these findings depend largely on the extent to which the observed associations remain long after use of hormonal contraceptives has ceased, and this cannot be evaluated properly from published data.

Low risk of cervical cancer during a long period after negative screening in the Netherlands.

A condition for effective cervical cancer screening is a low incidence of cervical cancer after negative screening compared to that in the absence of screening. This relative risk was studied for the period 1994–1997 in the Netherlands and compared with previous studies. All cases of invasive cervical cancer diagnosed from 1994 to 1997 in the Netherlands were related to woman-years at risk, stratified by age, number of preceding negative screenings and time since the preceding negative screening. These incidence rates were compared with that before screening started in the Netherlands. The relative risk increases from 0.13 in the first year after screening to 0.24 after more than 6 years after screening for women with one previous negative screening. These figures reduce to 0.06 and 0.18, respectively, for women with two or more previous screenings. However, these estimates are less favourable when account is taken of the likely decrease in risk for cervical cancer in the period studied. Our data show a low relative risk of cervical cancer for several years following the last negative Pap smear. However, the denominator of the relative risk, that is, the incidence without screening, may have been overestimated. This applies also to the IARC multicountry study, and may have caused too optimistic expectations about the effectiveness of cervical cancer screening.

#3 Parity, age at first birth, and risk of invasive cervical cancer

PURPOSE: The roles of parity and age at first birth as risk factors for cervical cancer remain unclear, although several studies in different populations have examined this question. We performed meta-analyses to predict relative risk of invasive cervical cancer as functions of parity and of age at first birth by fitting a variety of models. METHODS: We fit models relating the logarithm of relative risk for cervical cancer to parity and to age at first birth. Parity models were based on parity-specific relative risk estimates from 21 studies published between 1985 and 2001. Age at first birth models were based on corresponding data from 11 studies published during the same time period. Some models included covariates indicating whether individual studies adjusted for human papilloma virus (HPV) status, number of sex partners, age at first birth (parity models only), and/or parity (age at first birth models only). RESULTS: Relative risk for cervical cancer was found to increase with parity, at a declining rate (i.e., the greatest increase in risk was between parity 0–1, with consistently smaller increases thereafter). Relative risk for first birth at ages ⩾17 was significantly lower than relative risk for first birth at age 13, but no significant relationship was found between relative risk and age at first birth for first birth at ages ⩾17. Overall, indicators of whether studies adjusted for covariates were unable to explain the large variations among study results. CONCLUSION: Risk of invasive cervical cancer was associated with increasing parity, with the greatest increase in risk with the first birth. Risk was decreased for first birth at age 17 compared to 13; for first birth at ages ⩾17, we were unable to derive a quantitative relationship between age at first birth and relative risk for cervical cancer.

A population-based prospective study of Chlamydia trachomatis infection and cervical carcinoma.

Persistent human papillomavirus (HPV) infection is an established cause of cervical cancer, but the role of other sexually transmitted agents, most notably Chlamydia trachomatis, has not been well defined. The women participating in the population-based cervical cancer screening program in Västerbotten county of Northern Sweden were followed up for up to 26 years to identify 118 women who developed cervical cancer after having had a normal Pap smear (on average 5.6 years later; range 0.5 months-26 years). As controls, we selected another 118 women who were matched by birth cohort, time-point of sampling of the baseline normal smear and who had a normal smear at the time when the corresponding case was diagnosed with cancer. The Pap smears and cervical cancer biopsies were analyzed by PCR for C. trachomatis DNA and for HPV DNA. At baseline, C. trachomatis DNA was present in 8% of cases but not among any one of the controls. The relative risk for cervical cancer associated with past C. trachomatis infection, adjusted for concomitant HPV DNA positivity, was 17.1 (95% CI 2.6-infinity). The presence of C. trachomatis and of HPV were not interrelated. Whereas C. trachomatis was primarily found in specimens taken many years before cancer diagnosis, HPV DNA was associated with a short lag time before cancer diagnosis. Whereas most women who were HPV DNA-positive in the prediagnostic smear were also positive for the same virus in the cervical cancer biopsy, none of the women were positive for C. trachomatis in both the prediagnostic smear and in the subsequent cervical cancer. In conclusion, a prior cervical C. trachomatis infection was associated with an increased risk for development of invasive cervical cancer.

Risk of invasive cervical cancer associated with polymorphic HLA DR/DQ haplotypes.

The genes encoding human leukocyte antigens (HLA) have shown to be associated with cervical neoplasia. To obtain reliable data on HLA associations with cervical tumors, the study should be performed within a strictly defined cohort. To investigate the population attributable risk of cervical cancer associated with the HLA class II haplotypes DR15 and DQ6 (DQA1*0102 and DQB1*0602), we performed a nested case-control study of 85 women who developed invasive cervical cancer and 120 healthy women from a population-based cohort of Swedish women. The relative risks of cervical cancer among DR15 and DQ6-positive women were 3.73 [confidence interval (CI): 1.8-7.4] and 4.33 (CI: 2.1-8.5), corresponding to population attributable proportions of 27.9% and 30.8%, respectively. A susceptibility locus in the HLA class II region is involved in a substantial fraction of the etiology of cervical cancer.

Risk of cervical cancer subsequent to a positive screening cytology: follow-up study in Finland

The purpose of the study was to estimate subsequent incidence of cervical cancer among women with positive cytology followed by negative histology. This was a longitudinal cohort study involving about 80,000 women with class II, III, IV or V cytology at the organized mass screening in Finland in 1971 1990. Follow-up through the Finnish Cancer Registry started from the fifth month following the initial screening and ended on December 31, 1995. Standardized incidence ratios (SIR) of invasive cervical cancer varied from 2.2 (class II) to 19 (class V), and SIRs of preinvasive lesion varied from 3.0 (class II) to 20 (class V) compared to the risk among the total Finnish female population of same age and calendar period. The relative risk was greatest during first years of follow-up for both preinvasive and invasive cervical lesions, and it remained significantly high over 5 years of follow-up. For women with class II cytology there were peaks in relative risk in the years of subsequent rescreenings. Women with positive cytology have a high relative risk of cervical cancer even when excluding the cancers found at screening; the high relative risk is persistent for more than 5 years, and therefore these women should be kept under close surveillance and repeated smears should be taken with relatively short intervals.

Gynaecological Infections as Risk Determinants of Subsequent Cervical Neoplasia

A longitudinal cohort study was carried out to determine whether gynaecological infections other than human papillomavirus (HPV) are also related to the subsequent increased risk of cervical neoplasia. The study comprised 19114 women attending the organized mass screening in Finland in 1985-1990 with cytologically detected HPV, Actinomyces, herpes simplex, Trichomonas vaginalis, or yeast. The women were followed-up for subsequent preinvasive lesions and invasive cancers until the end of 1994 by linkage to the nation-wide Cancer Registry. Standardized incidence ratios (SIR) with rates for the whole of Finland as reference and 95% confidence intervals (CI) were estimated. Trichomonas vaginalis and HPV were associated with a high relative risk of cervical cancer, SIR 6.4 (CI 3.7-10, preinvasive lesion and invasive cancer combined) and SIR 5.5 (CI 4.2-7.2, preinvasive lesion and invasive cancer combined), respectively. Herpes simplex was rarely detected, but the highest and statistically most significant point estimate was observed (SIR 12, CI 2.4-34, preinvasive lesion and invasive cancer combined). Neither Actinomyces nor yeast was associated with a significantly increased risk of cervical cancer. None of these results could be accounted for by the confounding effect of the other infections. Our results, based on a prospective design, lead us to propose that Trichomonas vaginalis and herpes simplex virus are also predictors for cervical neoplasia.

Aspects of Men's Sexual Behavior Affect Wives' Risk of Cervical Cancer

The results of a case-control study conducted at three hospitals in Thailand indicate that women whose husbands have unprotected intercourse with commercial sex workers are at increased risk of invasive cervical cancer. The study was part of a larger multinational World Health Organization analysis of the effects of hormonal contraception on various forms of cancer. The Thai study involved 225 married women with invasive squamous cell cervical carcinoma 791 controls and the husbands of women in both groups. The women had been married only once and had not had sexual relations with any man but their husbands. The husbands of 81% of cancer patients and 69% of controls reported they had visited a commercial sex worker. The relative risk of cervical cancer was 2.1 for women whose husbands had rarely or never used condoms with sex workers and also 2.1 when husbands had first visited a prostitute before the age of 20 years. The risk increased with increasing numbers of prostitute encounters. Only women whose husbands had a first encounter with a prostitute while in their teens or 20s had a significantly higher cervical cancer risk (1.6 and 1.8 respectively) than those whose husbands had not visited a prostitute at these ages; the risk increased to 1.7 and 1.9 respectively when condoms had rarely or never been used in these encounters by men in these two age groups. These findings suggest that a successful campaign to promote condom use in Thailand could reduce the cervical cancer rate by at least 23%.