High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up.

Human papillomavirus (HPV) causes cervical, vulvar, and vaginal cancers, precancerous dysplasia, and genital warts. We report data for the longest efficacy evaluation to date of a prophylactic HPV vaccine. In total, 552 women (16-23 years) were enrolled in a randomised, placebo-controlled study of a quadrivalent HPV 6/11/16/18 L1 virus-like-particle vaccine with vaccination at months 0, 2, and 6. At regular intervals through 3 years, subjects underwent gynaecologic examination, cervicovaginal sampling for HPV DNA, serum anti-HPV testing, and Pap testing, with follow-up biopsy as indicated. A subset of 241 subjects underwent two further years of follow-up. At 5 years post enrollment, the combined incidence of HPV 6/11/16/18-related persistent infection or disease was reduced in vaccine-recipients by 96% (two cases vaccine versus 46 placebo). There were no cases of HPV 6/11/16/18-related precancerous cervical dysplasia or genital warts in vaccine recipients, and six cases in placebo recipients (efficacy = 100%; 95% CI:12-100%). Through 5 years, vaccine-induced anti-HPV geometric mean titres remained at or above those following natural infection. In conclusion, a prophylactic quadrivalent HPV vaccine was effective through 5 years for prevention of persistent infection and disease caused by HPV 6/11/16/18. This duration supports vaccination of adolescents and young adults, which is expected to greatly reduce the burden of cervical and genital cancers, precancerous dysplasia, and genital warts.

Knowledge about the prevention of sexually transmitted diseases: a longitudinal study of young women from 16-23 years of age.

OBJECTIVES: To describe knowledge and attitudes regarding sexually transmitted diseases (STD) in the same women followed longitudinally for 7 years from teenage years to early adulthood, and to relate the findings to sexual behaviour. METHODS: A face to face interview and a questionnaire were completed by 79 young women when they were 16, 18, and 23 years old. RESULTS: The questionnaire, testing knowledge about the mode of transmission and prevention of STD, gave a total score of correct answers varying between 44% and 64%, with less knowledge about human papilloma (HPV) and herpes viruses than about chlamydia. Awareness of the possibility of asymptomatic transmission was low. The highest scores were obtained at the age of 18 years. Experience of many partners, a history of STD, smoking, and more frequent use of alcohol were associated with a higher level of knowledge. CONCLUSIONS: Knowledge was fairly good and consistent, but was more often incorrect regarding viral infections and the possibility of asymptomatic transmission, and in total did not ensure an adequate protective behaviour. A higher level of knowledge was associated with a more risky behaviour, indicating that information was best received by those who could identify with the problem.

Seropositivity to human herpesvirus 8 in relation to sexual history and risk of sexually transmitted infections among women.

The mode of transmission of human herpesvirus 8 (HHV8) was investigated in two seroepidemiological studies of Swedish women who completed a questionnaire about sexual behavior. Seropositivity for HHV8 antibodies, measured using an indirect immunofluorescence assay, was linked to a high number (>10) of sexual partners (P < 0.004). It also correlated strongly with a history of other sexually transmitted diseases (STD; P < 0.0001), in particular with a history of Chlamydia trachomatis infection and condyloma acuminata. There was appreciable HHV8 seropositivity already among virginal or monogamous women (9%). In summary, HHV8 transmission to women in Sweden may occur nonsexually. When sexual transmission occurs, it appears to be associated with high risk-taking sexual behavior.

The pap-smear history of women with invasive cervical squamous carcinoma. A case-control study from Sweden.

BACKGROUND: Screening by cytology is a potentially highly effective procedure for preventing carcinoma of the uterine cervix. To elucidate any weaknesses in the screening procedure in a Swedish county where screening started many years ago, the detection of invasive cervical squamous cell carcinoma was compared to the prior cytological screening. METHODS: On the basis of the complete Pathology data files, including cytology and histology, all 112 women with invasive cervical squamous carcinoma were compared to 112 matched controls from the Swedish Population Register, regarding attendance rate and results of Pap-smears prior to the date of discovery of an invasive carcinoma in the case. RESULTS: Almost as many cases as controls had a history of pap-smear testing, but the cases had significantly more prior atypias registered. Only 16% of women with cervical carcinoma and younger than 60 years were lacking Pap-smear tests prior to the carcinoma diagnosis, but 46% had former atypias registered. More than half of them presented, however, a negative Pap-smear test less than three years before the diagnosis. Among the controls, 10% were lacking prior Pap-smears and only 9% had former atypias registered. CONCLUSION: The policy for follow-up and treatment of cervical dysplasias has to be improved in order to achieve a further reduction of the incidence of invasive carcinoma.

Seroepidemiology of human papillomavirus type 73: a sexually transmitted low-risk virus.

Human papillomavirus type 73 (HPV 73) has been detected in some invasive cervical cancers and has been cloned from a squamous-cell carcinoma of the esophagus, but the epidemiology of this infection and its associated risk of cancer is unknown. We investigated the seroepidemiology of this virus using virus-like particles. The IgG response to HPV 73 appeared to be HPV type-specific, since a comparison of HPV 73 antibody levels before and after infection with HPV 6, 11, 16, 18 or 33 found no evidence of cross-induction of HPV 73 antibodies and since there was little correlation between the antibody levels to HPV 73 and the other 5 investigated HPV types. In both a cross-sectional serosurvey that included 274 women and a 7-year follow-up study that enrolled 98 women, HPV 73 seropositivity was found to be strongly dependent on the number of lifetime sexual partners [OR for > 4 vs. 0 to 1 partners: 6.0 (95%CI: 1.4-53.6) and 7.9 (95% CI: 2.8-28.3), respectively]. Finally, the risk for HPV 73 seropositive women to develop CIN was investigated in a prospective study nested in a cohort of 15,234 Swedish women. The population-based HPV 73 seroprevalence in Sweden was 14%. No excess risk for CIN was found (OR: 0.77). We conclude that HPV 73 is a mainly sexually transmitted, probably mostly transient, infection that does not confer any measurably increased risk for CIN development.

High risk genital papillomavirus infections are not spread vertically.

The Medline-indexed literature on risk factors for HPV infection and HPV transmission is critically reviewed. Principles for assay validation and interpretation, reliability of different study designs and principles for interpretation of conflicting reports are discussed. The conclusions arrived at can be summarised as: (1) There is overwhelming epidemiological evidence that the only quantitatively important mode of transmission of infection with oncogenic genital HPV types is sexual. (2) There is also evidence that benign genital HPV types can be transmitted sexually, but the epidemiological data on the benign virus types are less extensive and less clear. (3) Perinatal HPV transmission is unequivocally demonstrated only for the rare disease juvenile respiratory papillomatosis.

Immunoglobulin A, G, and M responses to L1 and L2 capsids of human papillomavirus types 6, 11, 16, 18, and 33 L1 after newly acquired infection.

OBJECTIVES: We performed a study to establish the pattern of serological reactivity for immunoglobulins (Ig), to capsids of human papilloma virus (HPV) after new HPV infection in two groups of subjects. METHODS: The pattern of serological reactivity after acquisition of infection with HPV was investigated by measuring IgA, IgM, and IgG antibodies to capsids containing L1 and L2 proteins of HPV types 6, 11, 16, 18, and 33 in longitudinal studies of groups with different patterns of sexual activity. Individuals who tested negative for HPV DNA by the polymerase chain reaction at enrolment, but who became HPV DNA positive during follow up, were examined for antibodies to HPV capsids by enzyme linked immunosorbent assay. One group consisted of 15 young girls (with eight controls who remained HPV DNA negative) who were becoming sexually active and the other comprised 12 male (with five controls) and 35 female (with seven controls) heterosexual attenders of a sexually transmitted disease clinic who had had multiple sexual partners. RESULTS: The sexually inexperienced girls showed IgA and IgG responses, but seldom an IgM response to infection with HPV types 6/11, 16, and 18. No consistent pattern of serological reactivity was apparent for the heterosexuals with multiple partners. The lack of association between current HPV DNA positivity and detectable antibodies in these individuals was possibly related to the duration of infection or to prior exposure to HPV. For the latter group serological reactivity to HPV capsids was significantly greater in women than in men (p = 0.001, p = 0.003, and p = 0.024, for IgG to HPV 6, 11, and 16, respectively). CONCLUSION: The sex difference in antibody response detected in previous studies with assays based on peptide antigens was thus corroborated in the present study with capsid based serological assays. This sex difference might reflect a difference in sexual activity and prior exposure to HPV between men and women in this particular group.

Epstein-Barr virus DNA in the uterine cervix of teenage girls.

OBJECTIVES: To: (i) evaluate longitudinally the prevalence of Epstein-Barr virus (EBV) DNA in the cervix of healthy teenage girls, (ii) relate the presence of cervical EBV DNA to virginity or sexual experience, and (iii) relate the occurrence of cervical EBV DNA to the presence of specific IgG antibodies to EBV virus capsid antigen (EBV-VCA) in serum and to signs of genital infection. MATERIAL AND METHODS: Thirty-six teenage girls were followed for 2 years between the ages of 16 and 18 years. A sexual history was taken and a gynecological examination was performed on each occasion. The presence of EBV DNA in the cervix and of EBV VCA antibodies in serum was determined on each occasion. RESULTS: Coitus debut was reported by 23/36 girls (64%) and by 31/36 (86%) at 16- and 18-years of age, respectively. Two girls (only one with sexual debut) harbored EBV DNA in the cervix at 16 years of age. At the age of 18, no EBV DNA was found in these two girls, but another three girls carried EBV DNA in the cervix. All were sexually active and reported 1, 4 and 7 life-time sexual partners respectively. Serum EBV-VCA antibodies were found in 83% of the 16-year old girls and in 89% of the 18-year old girls (no significant difference between sexually experienced and virginal girls at either age). All the girls with cervical EBV DNA had antibodies against EBV-VCA. None of the girls with EBV DNA were found to carry HPV DNA or have a chlamydial infection in the cervix at any time during the study. There was no significant difference in the number of girls with a cervix secretion predominated by leucocytes between girls with positive and negative cervical EBV DNA samples. CONCLUSIONS: We conclude that among these healthy teenage girls the non-sexual route of transmission of EBV is more plausible than the sexual one.

[Sexuality and STD infections among teenage girls. "Unprotected sex" is common in spite of sufficient knowledge about the risks]. / Sexualitet och STD-infektioner bland tonårsflickor. "Osäkert sex" vanligt trots goda kunskaper.

A 2-year prospective study of sexual behaviour transmitted diseases (STDs) in 98 healthy 16-year-old schoolgirls showed human papillomavirus (HPV) infections to have spread rapidly among sexually active girls, whereas none of the virgins manifested HPV DNA in the cervix or anti-HPV 16 or anti-HPV33 antibodies in serum. A high level of knowledge of STDs and their prevention failed to induce appropriate behaviour among the sexually active.

Human papillomavirus deoxyribonucleic acid in cervix only detected in girls after coitus.

In a prospective cohort study on the prevalence of HPV in a group of female Swedish students, we obtained repeated cytological specimens during a period of 2 years, for cytological diagnosis and PCR detection of HPV. The group comprised 98 girls, sampled between 15 and 17 years, and 82 of them completed the study. The girls were also followed every sixth month by a structured face-to-face interview regarding sexuality. Only the sexually experienced girls harboured HPV-DNA in the cervix with a cumulative prevalence of 37% and HPV16 was the most common type encountered. Almost half of the infected girls were lacking any clinical or subclinical signs of HPV infection. There was a positive correlation between the presence of HPV and the number of coital partners. The time period since coitarche also had importance for the HPV detection rate.

Age of sexual debut related to life-style and reproductive health factors in a group of Swedish teenage girls.

AIM: To compare life-style and reproductive health care factors in girls with a coitus debut < 15 years of age and girls with a later debut. METHODS: Girls resident in the municipality of Karlstad, Sweden, starting their upper secondary school education were invited to attend the teenage clinic during two years (five visits). Gynecological examinations were performed and questions were asked about possible symptoms, sexual activity, contraception and sexually transmitted diseases. RESULTS: Ninety-eight girls accepted the invitation to participate and 88 girls completed all visits (mean age on admission 16 years). Median age for coitarche was 16 years. A sexual debut < 15 years was reported by 17 girls (19.3%), 54 (61.4%) had their debut > or = 15 years and 17 girls (19.3%) had not had their sexual debut on completion of this study. Girls with an early sexual debut had a greater number of sexually transmitted diseases (p < 0.05) and more cervical atypias (p < 0.05), and more often had a menarcheal age < 13 years (p < 0.05), > two brothers and/or sisters (p < 0.01), were more often not living with their parents (p < 0.01) and reported a greater number of life-time partners (p < 0.06) than the remainder, Girls with a sexual debut < 15 years started drinking alcohol earlier than others (p < 0.01). There was a greater proportion of smokers among girls with an early sex debut compared to the remainder (p < 0.05). CONCLUSIONS: Early sexual debut is associated with an earlier menarche and a more premature adult life-style and is an important indicator for continued risk behavior regarding reproductive health.

Comparison of development of serum antibodies to HPV16 and HPV33 and acquisition of cervical HPV DNA among sexually experienced and virginal young girls. A longitudinal cohort study.

OBJECTIVES: To study the importance of sexual activity and early coitus debut on the risk for acquiring infection with human papillomavirus (HPV) type 16 or 33. STUDY DESIGN: Ninety-eight healthy adolescent girls were followed up with consecutive interviews and donations of serum and cervical brush samples during 2 years. RESULTS: Fourteen percent of sexually experienced girls had serum immunoglobulin G to HPV16 and/or HPV33 capsids, and 14% also had cervical HPV16 or HPV33 DNA. Seropositivity for HPV correlated with detection of cervical HPV DNA. None of the 36 girls without coital experience was seropositive or harbored cervical HPV DNA. Seropositivity for HPV was correlated strongly with the number of sexual partners: Odds ratio for > 1 sexual partner was 16.3 (P < 0.001), and for early coitus debut (younger than 17 years of age), it was 14.3 (P < 0.002). CONCLUSIONS: Both HPV serology and HPV DNA testing indicated that the number of sexual partners and earliness of coitus debut determined the risk for acquiring HPV infection and that nonsexually transmitted infections are rare or nonexistent among adolescent girls.

The relationship between knowledge about sexually transmitted diseases and actual sexual behaviour in a group of teenage girls.

PURPOSE: To assess longitudinally the relationship between knowledge about sexually transmitted diseases (STDs) and sexual behaviour, contraceptive use, STD protection and social class in a group of Swedish teenage girls. METHODS: Girls starting their upper secondary school education were invited to attend a teenage clinic during a period of 2 years (5 visits). Questions were asked about family situation, sexual activity, contraceptives, STD protection and knowledge about STD. Gynaecological examinations were performed on entry and completion, and when necessary during the observation period. RESULTS: Eighty-eight girls completed all visits during the observation period. At 16 years of age there were no significant differences in knowledge about various STD and STD protection between girls from different social classes or with respect to coital experience, age of coitarche and the subsequent number of sexual partners at 18 years of age. At 18 years of age there was a better knowledge about STDs and the need for STD protection (p < 0.01) among girls with coital experience compared with those who had no coital experience. Girls reporting many lifetime partners were best informed, but in spite of solid knowledge they did not protect themselves from infection. Even though 34% of the girls with coital experience were found to harbour a STD during the course of this study, almost all girls denied the possibility of having acquired or transmitted an infection. CONCLUSIONS: Although girls were well-informed about sexually transmitted diseases and knew how to avoid infections this knowledge had little influence on behaviour.

Prevalence of antibodies to herpes simplex virus types 1 and 2, Epstein-Barr virus and cytomegalovirus in teenage girls.

Seropositivity to herpes virus type 1 (HSV-1), herpes virus type 2 (HSV-2), cytomegalovirus (CMV) and Epstein-Barr virus (EBV) was estimated in a group of 98 16-year-old Swedish girls. Antibodies to HSV-1 were seen in 41% of the girls and to HSV-2 in 1%, and antibodies to CMV in 45 and to EBV in 82%. In girls with coitus experience, there was significantly higher prevalence of HSV-1 and EBV antibodies, compared with girls with no sexual contact. The age of coitarche or number of coitus partners did not affect the rate of seropositivity. During 2 years of follow-up, 13 girls seroconverted. All but one EBV-seroconverting girl, were sexually active, and no girl converted for more than one type of virus. We concluded that transmission of herpes viruses is common in adolescence, and sexuality, even with regard to its close association with kissing, is one important determinant.

Genital papillomavirus infection in women treated for chlamydial infection.

Samples for chlamydia testing were taken from 298 and PAP smear from 284 non-pregnant sexually active young women in a midwife-run family planning dervice. Chlamydia was found in 36 (12.1%). Three women (1.1%) had cytological atypia corresponding to CIN I or II. Koilocytosis was seen in 9 smears (2.8%). Thirty-two of the chlamydia-positive women were followed for a mean of 15 months by a gynaecologist with chlamydia tests, colposcopy, PAP-smears and in some cases biopsies. There were 7 reinfections with chlamydia (22%). Signs of genital papillomavirus infection (GPVI) were found in 24 of the 32 chlamydia cases during follow-up. Twenty chlamydia-positive patients had abnormal colposcopy, 15 of them had other changes suggestive of GPVI, seven of these had CIN I or II. At follow-up 6 patients had cytologic atypia (18.8%) compared with the average 1.5% in this department during this period. Among 12 patients with normal colposcopy there were no cytological changes. Chlamydial infection calls for increased alertness regarding abnormal vaginal cytology even among young patients not commonly included in PAP smear screening programmes.

Sexually transmitted diseases--knowledge and attitudes among young people. Developments in Sweden between 1986 and 1988.

Pupils aged 18 to 19 years at colleges and technical schools in a small town and a rural area filled in questionnaires concerning sexually transmitted diseases (STD) in May 1986 and May 1988. The questions covered knowledge and sources of information about STD. The influence of knowledge on attitudes and actual behavior was studied. Knowledge about STD was fairly good and increased between the two study periods. Schoolteachers and the media were important sources of information. Girls knew more than boys, and more often discussed STD with adults and friends. Small differences emerged between the urban and rural areas and between pupils attending theoretical and practical courses. Attitudes seemed to change with time but it is not clear whether this has resulted in changes in actual behavior.