Little research has been conducted on the long‐term value of human papillomavirus (HPV) testing after conization. We investigated whether cytology adds to the value of a negative HPV test for long‐term prediction of cervical intraepithelial neoplasia grade 2 or worse (CIN2+). In addition, we compared risk of CIN2+ following a negative HPV test in women after conization with that in women from the general population. During 2002–2005, 667 women treated for CIN2+ were tested for HPV and cytology 46 months after conization. Only HPV‐negative women were included. Women participating in routine screening were age‐matched with post‐conization HPV‐negative women, leaving 13,230 and 477 women, respectively, for analysis. By linkage to the Pathology Data Bank, we identified all cases of CIN2+ by December 2013. The 3‐, 5‐, 8‐ and 10‐year risks for CIN2+ were 0.7, 0.9, 2.8 and 5.7% after a negative HPV test and 0.5, 0.8, 2.9 and 6.1% in HPV and cytology‐negative women. HPV‐negative women in the general population had similar 3‐year and 5‐year risks of 0.4 and 1.0%; thereafter, they had lower risks of 1.9% at 8 years and 2.7% at 10 years. Our results indicate that HPV testing may be used as a test of cure after conization. In the first 5 years after testing, the risk for CIN2+ of women who were HPV‐negative at 34 months after conization was similar to that of HPV‐negative women in the general population. After 67 years, however, women who have undergone conization may be at higher risk for CIN2+.

OBJECTIVE:Adequate follow-up of women who have undergone conization for high-grade cervical lesions is crucial in cervical cancer screening programs. We evaluated the performance of testing for high-risk human papillomavirus (HPV) types, cytology alone, and combined testing in predicting cervical intraepithelial neoplasia grade 2 or worse (CIN2+) after conization.DESIGN:Prospective cohort study.SETTING:Denmark.POPULATION:667 women attending for conization.METHODS:Cervical specimens were collected during 2002-2006 at first visit after conization for cytological examination and Hybrid Capture 2 detection of high-risk HPV. The women were passively followed until 2 years after first follow-up visit by linkage to the nationwide Pathology Data Bank.RESULTS:At first visit after conization (median time, 3.4 months), 20.4% were HPV-positive and 17.2% had atypical squamous intraepithelial lesions or more severe cytology (ASCUS+). The 2-year incidence of CIN2+ after conization was 3.6%. Sensitivity for detection of CIN2+ after conization was 81.0% [95% confidence interval (CI) 58.1-94.6] for positive cytology (ASCUS+ threshold) and 95.2% (95% CI 76.2-99.9) for HPV testing and for combined testing. Specificity of ASCUS+ cytology (85.2%; 95% CI 82.0-88.0) was higher than that of HPV testing (82.4%; 95% CI 79.0-85.4) and markedly higher than that of combined testing (73.2%; 95% CI 69.3-76.8). The margin status had no significant added value.CONCLUSIONS:Testing for high-risk HPV three to four months after conization is more sensitive than ASCUS+ cytology for identifying women at risk for relapse of CIN2+ within 2 years. Further studies are needed to evaluate whether HPV testing could be a stand-alone test in follow up after conization.

Objective. Women with early cervical cancer or intraepithelial neoplasia grades 2 and 3 (CIN2+) are treated by conization; however, they still have a higher risk for subsequent CIN2+ than the general female population. Persistence of high-risk (HR) human papillomavirus (HPV) is a key factor in the development of CIN2+. We investigated persistence and reappearance of type-specific HR HPV infection after conization and evaluated possible co-factors.Methods. During 2002-2006, cervical swabs from 604 women were collected before conization, at 4-6 months and at 8-12 months after conization. HPV was detected by HC2 and genotyped by LiPAv2. Information on co-factors was collected through a' questionnaire. Associations were assessed by multivariate logistic regression analysis.Results. HR HPV persistence rate was 9.5%. The alpha 5/6 species were more likely to persist than alpha 9 species (OR, 2.28; 95% CI, 1.11-4.70). For single infections, a doubling in viral load at enrolment increased the risk for persistence by 36% (95% CI, 1.13-1.63). In addition, margin status was associated with risk of persistence. Smoking, oral contraceptive use and severity of the cervical lesion did not significantly affect persistence. Among the HPV infections that had cleared, 2.2% reappeared.Conclusion. Our study indicates that viral load is important in predicting HPV persistence. The alpha 5/6 species were most likely to persist. However, most of these HPV types have a lower carcinogenic potential than the alpha 7/alpha 9 species and may be by-standers. Further studies are needed to assess whether pre-conization viral load can also predict subsequent CIN2+. (C) 2013 Elsevier Inc. All rights reserved.

In spite of the success of cervical cytology as a cancer-screening tool, it has important limitations, and human papillomavirus (HPV) testing may be valuable in future screening. The majority of women in screened populations, who test HPV positive, will have a concurrent normal smear, and we need more information about the risk for subsequent high-grade cervical lesions in these women. We examined 8,656 younger women (22-32 years old) and 1,578 older women (40-50 years old) who were followed for development of cervical neoplasia (cytology and/or histology) through the Danish Pathology Data Bank. We estimated the proportion of women developing cervical lesions of different types before a given time point as a function of time. Among women with normal cytology and positive high-risk Hybrid Capture 2 (HC2) test, 17.7% and 24.5% of younger and older women, respectively, had a subsequent abnormal Pap smear within 5 years. The risk of CIN3 or cancer within 10 years among younger women with positive HC2 test was 13.6% (10.9-16.2) and 21.2% (2.7-36.1) among older women. An analysis among younger women also being HC2-positive 2 years before baseline showed a subsequent 10-year risk of > or =CIN3 of 18% (14.6-21.5). Among older women where HPV may be added to general screening, the estimated absolute risk of > or =CIN3 in HC2-positive women was more than 20% within 10 years. These results indicate that even a single positive HPV test in cytologically negative women is substantially predictive of high-grade CIN and suggest that HC2 testing can help stratify women into different risk categories.

Background. Infection with human papillomavirus is considered a necessary factor in developing high-grade squamous intraepithelial lesions of the cervix. However, most human papillomavirus positive women do not develop high-grade squamous intraepithelial lesions and other factors may be important for this transition. The objective of the present study was to examine if smoking and alcohol intake are associated with the risk of developing high-grade squamous intraepithelial lesions in women positive for high-risk human papillomavirus types. Methods. We used baseline information on exposures on 548 high-risk human papillomavirus positive women with normal cytology, comparing 94 women who developed high-grade squamous intraepithelial lesions with 454 women who remained cytologically normal. Logistic regression was applied for statistical analysis. Results. Compared with never smokers, the odds ratio for high-grade squamous intraepithelial lesions among current smokers was 1.99 (95% CI: 1.21-3.28). Among current smokers, number of cigarettes, years of smoking, and early age at smoking initiation were associated with increased risk. However, when modeled simultaneously, it seemed that smoking duration and age at smoking initiation were more associated with risk of high-grade squamous intraepithelial lesions than amount of smoking. Alcohol intake was not associated with risk of high-grade squamous intraepithelial lesions among these women. Conclusion. Smoking is associated with an increased risk of developing high-grade squamous intraepithelial lesions in women who are infected with oncogenic human papillomavirus.

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.

Based on interview data from 10841 Danish women aged 20 to 29 years, determinants for non-use of contraception at first intercourse (NU) were studied. One-fourth of the women (n = 2704) reported NU, whereas condoms and oral contraceptives were used by, respectively, 59% and 15%. NU decreased with the birth year of the first male partner (OR = 3.6; 95% CI: 2.8-4.8 for or=17 years) at the expense of both oral contraception and condom use. Finally, NU was found to predict high-risk sexual behavior in terms of subsequent multiple sex partners, non-use of condoms, and induced abortion.

Objectives: Genital infection with certain types of human papillomavirus (HPV) is the most important risk factor for cervical cancer. The male sexual partner is supposed to be the vector of the infection. However, the knowledge of risk factors for genital HPV DNA in men is limited. The objective of this paper is to study the risk factors for HPV infection in men and to compare them with those found in women, including the study of whether there are different risk profiles for oncogenic and non-oncogenic HPV types. Methods: From a sexually transmitted diseases (STD) clinic in Denmark, 216 men were consecutively included. A personal interview was done and material for genital HPV DNA detection was obtained with swabs. HPV DNA was detected by polymerase chain reaction (PCR). Odds ratios (OR) for HPV as well as for oncogenic and non-oncogenic types separately were computed with a 95% confidence interval (CI) by means of unconditional multiple logistic regresssion. Results: The most important predictors of any HPV were lifetime number of sex partners (OR = 4.3; 95% CI 1.4 to 13.1 for 25–39 v 1–9 partners), young age, and being uncircumcised. The most important risk factor for oncogenic HPV types was lifetime number of partners, whereas number of partners in the past year and ever having genital warts were risk factors for the non-oncogenic HPV types. Young age predicted risk of both oncogenic and non-oncogenic HPV types. Conclusions: Most risk factors for HPV DNA detection in men resemble those found in women. As in women, the risk factor profile for the oncogenic HPV types was different from that of the non-oncogenic HPV types.

Genital human papillomavirus (HPV) infection is generally considered to be sexually transmitted. However, nonsexual spread of the virus has also been suggested. The goal of this study was to assess: (a) the role of sexual intercourse in the transmission of HPV; (b) the determinants for seroconversion; and (c) the correlation between HPV DNA, abnormal cervical cytology, and serological response to HPV16. One hundred virgins and 105 monogamous women were randomly selected from a population-based cohort study in Copenhagen, Denmark, in which the women were examined twice with 2-year interval (interview, cervical swabs, Pap smear, blood samples). The presence of HPV DNA was determined by GP5+/6+ primers based HPV-PCR-EIA. HPV 16 virus-like particles (VLP) antibodies were detected by ELISA. All of the virgins were both HPV DNA negative and seronegative to VLP16, except for one woman who was weakly HPV 6 DNA positive. Only those virgins who initiated sexual activity became HPV DNA positive and/or VLP16 positive. The most important determinant of HPV DNA acquisition was the number of partners between the two examinations. The only significant risk factor for HPV 16 VLP seroconversion among women acquiring HPV DNA was HPV type. Our results show that sexual intercourse is important in the transmission of HPV, and that HPV 16 VLP seroconversion and the development of cervical lesions only occur after HPV transmission. Remarkably, no cervical lesions were found in HPV 16 DNA positive women who had seroconverted. Although based on small numbers, this may suggest that the development of antibodies had a protective effect.

BACKGROUND:The prevalence of the human papillomavirus (HPV) has been found to decrease with age, but whether this applies to all populations is not clear. Knowledge about the generalizability of this age dependency is important to understand the natural history of the infection, but may also have implications in relation to the use of HPV testing in cervical cancer screening.GOAL:To study the prevalence and risk factors for HPV infection in a selected population of female sex workers and to compare the results with persons with different sexual habits from two other populations in the same geographic area.STUDY DESIGN:A case-control study among 188 female sex workers from Copenhagen. Data were obtained by personal interviews. Cervical material was collected by a self-administered lavage kit, and HPV testing was done by means of GP5+/6+ primers based on HPV, polymerase chain reaction, enzyme immunoassay.RESULTS:Among sex workers, age was the most important risk factor for HPV infection. Number of private sex partners in the last 4 months was also a significant risk factor, and a protective effect of condom use was indicated.CONCLUSION:The HPV prevalence is declining in sex workers with age despite continuously high sexual activity, most likely indicating that an immune response is acquired over time.

International Journal of Gynecology & ObstetricsVolume 70, Issue S3 p. C144-C144 Invited presentation P3.17 physiology of reproductions P3.18.02 Association between number of recent sexual partners and the risk of acquiring cervical HPV is influenced by years since first intercourse E.I. Svare, E.I. SvareSearch for more papers by this authorS. Krüger Kjaer, S. Krüger KjaerSearch for more papers by this authorJ.E. Bock, J.E. BockSearch for more papers by this authorC.J.L.M. Meijer, C.J.L.M. MeijerSearch for more papers by this authorJ.M.M. Walboomers, J.M.M. WalboomersSearch for more papers by this authorA.J.C. van den Brule, A.J.C. van den BruleSearch for more papers by this author E.I. Svare, E.I. SvareSearch for more papers by this authorS. Krüger Kjaer, S. Krüger KjaerSearch for more papers by this authorJ.E. Bock, J.E. BockSearch for more papers by this authorC.J.L.M. Meijer, C.J.L.M. MeijerSearch for more papers by this authorJ.M.M. Walboomers, J.M.M. WalboomersSearch for more papers by this authorA.J.C. van den Brule, A.J.C. van den BruleSearch for more papers by this author First published: 11 December 2003 https://doi.org/10.1016/S0020-7292(00)85527-7AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume70, IssueS32000Pages C144-C144 RelatedInformation

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.

The most important risk factor for cervical cancer is genital infection with certain types of human papillomavirus (HPV). The presence of HPV was studied in archival smears from a random sample of women living in Greenland (GW) and Denmark (DW) having, respectively, a high risk and an intermediate risk for cervical cancer. Risk factors were also examined of the original 126 Danish and 129 Greenlandic archived smears collected during October and November 1988. 125 were located from each country including all abnormal smears. HPV DNA was isolated from the smears and detected by means of a consensus polymerase chain reaction (PCR) detecting a broad spectrum of genital HPV types. HPV was detected in all the abnormal smears and in 22 and 33% respectively of the cytological normal smears from DW and GW. Risk of HPV was significantly higher in smears from women who started sexual life relatively recently (respectively, ≤4 and ≤6 years ago in DW and GW) compared with ≥10 years ago (adjusted prevalence-OR: 9.3; 95% CI:2.2–39.2 in DW and 5.9; 95 % CI: 1.4–25.3 in GW). Among other important risk factors were age in both areas, lifetime number of sex partners and current smoking in DW and ever had gonorrhoea in GW. This study confirms the usefulness of the method as all abnormal smears were positive and, furthermore, the predictors for HPV presence in the normal smears corroborate with those found in recent studies of HPV in fresh cervical swabs. Thus, this method can be useful for large-scale epidemiological studies of HPV DNA in already sampled material.

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.

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.

Seroreactivity to human papillomavirus type 16 (HPV-16) virus-like particles (VLPs) in men attending clinics for sexually transmitted diseases (STDs) in Denmark (n = 219) and Greenland (n = 88) was compared with seroreactivity in women attending the same clinics and was furthermore related to epidemiologic variables and concurrent HPV DNA detection. Risk factors for male seropositivity in Denmark were lifetime number of sex partners, a history of STDs, and sexual preference and in Greenland were ever having had syphilis and years at school. Although men reported significantly more sex partners, the mean seroreactivity was significantly lower in men than in women: 0.50 and 0.75, respectively, in Denmark and 0.53 and 0.86 in Greenland (P = .0001). Male seropositivity was not correlated with concurrent HPV DNA detection, but only 15 Danish and 6 Greenlandic men had HPV-16 DNA. Presence of HPV-16 VLP antibodies appears to be a biomarker for exposure to genital HPVs in men but is less sensitive than in women.

Sexually transmitted genital human papillomavirus (HPV) infection, most often HPV 16, is considered the major etiologic determinant of cervical cancer. However, some studies have found relatively low prevalences of genital tract HPV DNA in some geographical areas, such as Greenland, that have high rates of cervical cancer. We sought to evaluate HPV 16 infection in high-risk cohorts using a serologic assay that assesses prior exposure as well as current infection and to compare the results with those obtained using a sensitive PCR-based HPV DNA assay. An ELISA based on HPV 16 virus-like particles was used to detect IgG serum antibodies in women attending sexually transmitted disease (STD) clinics in Nuuk, Greenland and Copenhagen, Denmark. Using a preassigned cut-off, 56% of Greenlandic and 41% of Danish women were seropositive (p = 0.02). In Greenlandic women, there was a non-significant increase in seropositivity with age, and odds ratios for seropositivity were similar for women with more than 5 lifetime sex partners. Seropositivity in the Danish women, however, increased linearly with increases in these 2 factors, which are likely correlates of lifetime exposure to genital HPVs. In contrast, any genital HPV DNA (HPV16 specifically) was detected in 24% and 36% of Greenlandic and Danish women, respectively and was most frequently detected in women below 20. The finding that HPV DNA prevalences, unlike seroprevalences, tended to decrease with increased lifetime risk of infection, provides an explanation for the lack of correlation between HPV DNA prevalences and cervical cancer risk in previous studies of high-risk populations.

It is not known whether DNA sequence variants of human papillomavirus type 16 (HPV-16) are distinct serotypes. To examine this question, the reactivities of women's sera from Zaire (n = 97) and Denmark (n = 123) were compared in IgG-specific ELISAs based on virus-like particles (VLPs) composed of the L1 major capsid protein derived from an HPV-16 variant common in central Africa (Z-1194) or one common in northern Europe (114K). These L1s differ in seven amino acids. There was a strong correlation between reactivity in the two assays for both sets of sera (correlation coefficients, 0.73 and 0.85 for Zairian and Danish sera, respectively). In only 1 serum was there evidence for a specific reaction to one but not the other VLP variant. The results support the conclusion that the virions of strains Z-1194 and 114K are serologically cross-reactive.

Several epidemiological investigations suggest an association between diet and prostatic cancer. The most consistent finding has been a risk-enhancing effect of a diet rich in fat, especially animal fat. There is some evidence that dietary fat acts in late prostatic carcinogenesis by promoting the progression from focal to clinical disease, and that this effect may be due to an influence on the hormonal system. Data on other dietary factors, especially vitamin A and beta-carotene, are equivocal. This is probably partly due to the fact that most of the epidemiological studies have been based on limited dietary information. It is unclear whether the nutritional status influences the development of prostatic cancer, and if so, which anthropometric measurements are associated with an increased risk. Future studies should aim at estimating dietary exposures more precisely than hitherto by using calibrated dietary assessment methods that permit adjustment for total energy intake and combining these with biochemical methods. It will also be important to further investigate relations between diet, nutritional status and the hormonal system.