Paul Poll

Type specific persistence of high risk human papillomavirus (HPV) as indicator of high grade cervical squamous intraepithelial lesions in young women: population based prospective follow up study

Abstract Objectives: To investigate the role of human papillomavirus (HPV) in the development of cervical neoplasia in women with no previous cervical cytological abnormalities; whether the presence of virus DNA predicts development of squamous intraepithelial lesion; and whether the risk of incident squamous intraepithelial lesions differs with repeated detection of the same HPV type versus repeated detection of different types. Design: Population based prospective cohort study. Setting: General population in Copenhagen, Denmark. Participants: 10 758 women aged 20-29 years followed up for development of cervical cytological abnormalities; 370 incident cases were detected (40 with atypical squamous cells of undetermined significance, 165 with low grade squamous intraepithelial lesions, 165 with high grade squamous intraepithelial lesions). Main outcome measures: Results of cervical smear tests and cervical swabs at enrolment and at the second examination about two years later. Results: Compared with women who were negative for human papillomavirus at enrolment, those with positive results had a significantly increased risk at follow up of having atypical cells (odds ratio 3.2, 95% confidence interval 1.3 to 7.9), low grade lesions (7.5, 4.8 to 11.7), or high grade lesions (25.8,15.3 to 43.6). Similarly, women who were positive for HPV at the second examination had a strongly increased risk of low (34.3,17.6 to 67.0) and high grade lesions (60.7, 25.5 to 144.0). For high grade lesions the risk was strongly increased if the same virus type was present at both examinations (813.0, 168.2 to 3229.2). Conclusions: Infection with human papillomavirus precedes the development of low and high grade squamous intraepithelial lesions. For high grade lesions the risk is greatest in women positive for the same type of HPV on repeated testing.

Human papillomavirus—the most significant risk determinant of cervical intraepithelial neoplasia

Sexual behavior has been consistently identified as a major risk factor for cervical cancer. Population‐based studies have demonstrated that risk related to sexual activity is mediated by human papillomavirus (HPV) infection. We conducted a case‐control study of 199 cases with low‐grade squamous intraepithelial lesions or high‐grade squamous intraepithelial lesions as defined by cytology and 1000 control women selected from an ongoing prospective cohort study in Copenhagen, Denmark. Furthermore, 131 women with equivocal smears (atypical squamous cells of undetermined significance) were examined as a separate borderline case group. At enrollment, all women had a personal interview and a gynecological examination including cervical swabs for HPV testing and a Pap smear. HPV testing was performed using a combination of general primer 5/6‐mediated and type‐specific polymerase‐chain‐reaction‐based methods. Cervical HPV infection was by far the most significant risk factor for cervical squamous intraepithelial lesions. The relationship with HPV was observed for all grades, while strength of association was greater for more severe lesions. The importance of the previously identified epidemiological risk factors for cervical neoplasia was also demonstrated. However, most of the effect of these factors could be explained by taking HPV infection into account, except for schooling and smoking. Non‐use of barrier contraceptives and smoking were the only significant risk factors in HPV‐positive women. In HPV‐negative women, a residual effect existed for different measures of sexual activity, and use of oral contraceptives and smoking constituted significant risk determinants. Overall, 66% of cases could be attributed to HPV; however, if the results were restricted to histologically confirmed high‐grade lesions, the proportion of cases that could be attributed to HPV infection increased to 80%.

Different risk factor patterns for high-grade and low-grade intraepithelial lesions on the cervix among HPV-positive and HPV-negative young women

Risk factors for cervical intraepithelial neoplasia have most often been studied in high‐grade lesions. Furthermore, in a high proportion of the studies, human papillomavirus (HPV), the most significant risk determinant of cervical neoplasia, was not taken into account when evaluating other risk factors. To compare risk factors for ASCUS (atypical cells of undetermined significance), LSIL (low‐grade squamous intraepithelial lesion) and HSIL (high‐grade squamous intraepithelial lesion), we conducted a case‐control study among 20 to 29 year‐old women participating in a prospective cohort study in Copenhagen. It included 131 women with ASCUS, 120 women with LSIL, 79 women with HSIL and 1,000 randomly chosen, cytologically normal, control women. All participants had a personal interview and a gynecological examination including a Pap smear and cervical swabs for HPV DNA detection using general primer‐mediated polymerase chain reaction. The most significant risk determinant of all 3 disease categories was the presence of genital HPV DNA. The risk factor pattern was nearly identical for ASCUS and LSIL, but differed significantly from that for HSIL. Stratified analysis by HPV‐status showed that, apart from, respectively, smoking and parity among HPV‐positive women, and smoking and number of sex partners among HPV‐negative women, no additional risk factors were observed for ASCUS and LSIL. In contrast, among HPV‐negative women with HSIL, long‐term use of oral contraceptives was the most important risk factor. However, our result should be taken with great caution as it is based on very small numbers, and as it is unknown whether the HPV‐negative lesions constitute a true entity. Among HPV‐positive women, the risk of HSIL was associated with e.g., years of sex life without barrier contraceptive use, early age at first genital warts and smoking. Whether the risk factors that are applicable only to HSIL represent factors related to progression remains unknown. Int. J. Cancer 76:613–619, 1998.© 1998 Wiley‐Liss, Inc.

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

Background and Objectives: 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. Goals: 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. Study Design: 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. Results: 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. Conclusions: 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.

What happens when organization of cervical cancer screening is delayed or stopped

Objectives: Many countries rely on opportunistic screening, and data on its effectiveness are asked for. We assessed the impact on cervical cancer incidence and mortality of opportunistic screening compared with organized screening. Setting: Women aged 30–64 in Denmark, 1973–2002; 16 counties with different screening strategies. Methods: Cumulative incidence and mortality rates for women aged 30–64 by county. Poisson regression of incidence and mortality rates by age, calendar period and county. Interaction between type of county and calendar period measured the difference between counties with screening organized early versus late in time. Results: A statistically significant interaction was found between type of county and calendar period (P=0.0151) for cervical cancer incidence, but not for cervical cancer mortality (P=0.9593). The interaction terms were not statistically significant when a comparison was made between a single county in which an organized programme was interrupted for an 11-year period and other counties. There was, however, a statistically significant increased incidence and mortality rates at the restart of the organized programme. Conclusion: Organization of cervical cancer screening accelerated the decline in cervical cancer incidence, compared with the trend in areas relying on opportunistic screening. No impact could be measured of the screening organization on cervical cancer mortality. A decade long stop of an organized screening programme was associated with a temporary increase in cervical cancer incidence and mortality. Coverage remains a key quality indicator in the ongoing modernization of screening technology.

Determinants for contraceptive use in young, single, Danish women from the general population.

Determinants for contraceptive use were studied in 5031, non-pregnant women aged 20-29 years from the general population in Denmark. Most women (72%) had never been pregnant, 34% had a history of a sexually transmitted disease, and 22% had ever had a legal abortion. Current contraception was most frequently condoms (60%) or oral contraceptives (33%). Among the women who used OCs or IUD, 32% reported additional condom use (double contraception). Important predictors of using one contraceptive method were lifetime number of sexual partners, parity, and age at first sexual intercourse for condoms and age for oral contraceptives. Also, women with a previous legal abortion were more likely to use condoms currently and women with a history of STDs were less likely to use condoms, but more likely to use OCs. Lifetime number of sexual partners was the only predictor of double contraception. Our data suggest a potential for reducing the number of unintended pregnancies and STDs in single women by increasing the information about the double principle in contraception.

Cervical cancer screening: Knowledge of own screening status among women aged 20-29 years

BACKGROUND Studies have shown that accuracy of self-reported screening for cervical cancer is not optimal. In order to improve womens knowledge of their screening status and in broader terms improve communication between patient and doctor the risk groups who require special attention with regard to information have to be identified. The purpose of this study was to identify lifestyle and socio-demographic determinants for denying screening when in fact it had been performed. METHODS A case-control study among 7,763 women aged 20-29 years from Copenhagen. Data were obtained by means of a personal interview using a standardized questionnaire and from a computerized pathology registry. Determinants for not knowing own screening status were identified using multiple logistic regression analysis. RESULTS In all, 13% of the women could not state correctly that they had been screened for cervical cancer. The major determinant was younger age (adjusted odds ratio: 5.8, for women aged 20-22 years compared with women aged 26-29 years). Other determinants included few Pap smears, increasing years since last Pap smear, no previous abnormal Pap smear, lower education, never having used oral contraceptives, and current smoking. CONCLUSIONS Knowledge about own screening status is not optimal in Denmark. Our study shows that doctors have to be extra careful with information to the youngest women and to certain other groups.

Abnormal Papanicolaou Smear: A Population-based Study of Risk Factors in Greenlandic and Danish Women

Possible risk factors for abnormal Papanicolaou smear were investigated in a population‐based cross‐sectional study. From Nuuk (Greenland) and Nykebing Falster (Denmark), random samples of 800 women aged 20–39 years were drawn. Totals of 586 and 661 women were included in Greenland and Denmark, respectively. All women went through a personal interview, and had a gynecologic examination including a PAP smear and cervical swab for HPV analysis. A blood sample was taken for analysis of HSV type specific antibodies. Multiple sexual partners was the most important risk factor for abnormal cervical cytology (OR = 4.2). An infectious etiology was also indirectly supported by a relatively protective effect of barrier contraceptive methods (OR = 0.6). The simultaneous finding of HPV 16/18 as a significant risk factor (OR = 2.4) cannot be taken uncritically as support for a causal effect of this HPV type, since such a relationship between cytological changes of the cervix and HPV infection could also emerge if the positive PAP smear was not just a measure of intra‐epithelial neoplasia but also an expression of the infection itself on the cervix.

Human Papillomavirus-The Most Significant Risk Determinant of Cervical Intraepithelial Neoplasia

Sexual behavior has been consistently identified as a major risk factor for cervical cancer. Population-based studies have demonstrated that risk related to sexual activity is mediated by human papillomavirus (HPV) infection. We conducted a case-control study of 199 cases with low-grade squamous intraepithelial lesions or high-grade squamous intraepithelial lesions as defined by cytology and 1000 control women selected from an ongoing prospective cohort study in Copenhagen, Denmark. Furthermore, 131 women with equivocal smears (atypical squamous cells of undetermined significance) were examined as a separate borderline case group. At enrollment, all women had a personal interview and a gynecological examination including cervical swabs for HPV testing and a Pap smear. HPV testing was performed using a combination of general primer 5/6-mediated and type-specific polymerase-chain-reaction-based methods. Cervical HPV infection was by far the most significant risk factor for cervical squamous intraepithelial lesions. The relationship with HPV was observed for all grades, while strength of association was greater for more severe lesions. The importance of the previously identified epidemiological risk factors for cervical neoplasia was also demonstrated. However, most of the effect of these factors could be explained by taking HPV infection into account, except for schooling and smoking. Non-use of barrier contraceptives and smoking were the only significant risk factors in HPV-positive women. In HPV-negative women, a residual effect existed for different measures of sexual activity, and use of oral contraceptives and smoking constituted significant risk determinants Overall, 66% of cases could be attributed to HPV; however, if the results were restricted to histologically confirmed high-grade lesions, the proportion of cases that could be attributed to HPV infection increased to 80%.