Sustained efficacy and immunogenicity of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine: analysis of a randomised placebo-controlled trial up to 6.4 years.

BACKGROUND: Prophylactic human papillomavirus (HPV) vaccines have to provide sustained protection. We assessed efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine up to 6.4 years. METHODS: Women aged 15-25 years, with normal cervical cytology, who were HPV-16/18 seronegative and oncogenic HPV DNA-negative (14 types) at screening participated in a double-blind, randomised, placebo-controlled initial study (n=1113; 560 vaccine group vs 553 placebo group) and follow-up study (n=776; 393 vs 383). 27 sites in three countries participated in the follow-up study. Cervical samples were tested every 6 months for HPV DNA. Management of abnormal cytologies was prespecified, and HPV-16/18 antibody titres were assessed. The primary objective was to assess long-term vaccine efficacy in the prevention of incident cervical infection with HPV 16 or HPV 18, or both. We report the analyses up to 6.4 years of this follow-up study and combined with the initial study. For the primary endpoint, the efficacy analysis was done in the according-to-protocol (ATP) cohort; the analysis of cervical intraepithelial neoplasia grade 2 and above (CIN2+) was done in the total vaccinated cohort (TVC). The study is registered with ClinicalTrials.gov, number NCT00120848. FINDINGS: For the combined analysis of the initial and follow-up studies, the ATP efficacy cohort included 465 women in the vaccine group and 454 in the placebo group; the TVC included 560 women in the vaccine group and 553 in the placebo group. Vaccine efficacy against incident infection with HPV 16/18 was 95.3% (95% CI 87.4-98.7) and against 12-month persistent infection was 100% (81.8-100). Vaccine efficacy against CIN2+ was 100% (51.3-100) for lesions associated with HPV-16/18 and 71.9% (20.6-91.9) for lesions independent of HPV DNA. Antibody concentrations by ELISA remained 12-fold or more higher than after natural infection (both antigens). Safety outcomes were similar between groups: during the follow-up study, 30 (8%) participants reported a serious adverse event in the vaccine group versus 37 (10%) in the placebo group. None was judged related or possibly related to vaccination, and no deaths occurred. INTERPRETATION: Our findings show excellent long-term efficacy, high and sustained immunogenicity, and favourable safety of the HPV-16/18 AS04-adjuvanted vaccine up to 6.4 years. FUNDING: GlaxoSmithKline Biologicals (Belgium).

Contraception.

Prescribing and reviewing contraceptive methods with adolescents involves a significant amount of time and resources. Health care providers need to be familiar with how teens think about sex and birth control, what their beliefs are, and how individual teens may make different choices based on their lifestyles. Barrier methods remain popular in that they are accessible and do not require a clinician visit. The hormonal choices need to be explained fully in plain language and selections based on these sessions made appropriately. Teens can be effective users of contraception if they are given the appropriate tools, access, and knowledge.

The potential role of an adult mentor in influencing high-risk behaviors in adolescents.

BACKGROUND: While mentorship programs, which connect adolescents with adults to whom they can turn to for help and advice, are proliferating in an attempt to prevent high-risk behaviors in teenagers, there are few data to show that mentorship actually makes a difference. OBJECTIVE: To determine if there is an association between having an adult mentor and high-risk behaviors in adolescents. HYPOTHESIS: Adolescents who have an adult mentor would be less likely to engage in high-risk behaviors than those without an adult mentor. DESIGN: Cross-sectional study. A self-administered, anonymous questionnaire was developed to assess demographics, involvement in risk behaviors, and the prevalence of a mentor in the life of a young person. PARTICIPANTS: A convenience sample of 294 adolescents, seen consecutively (93% of those approached), receiving outpatient medical care. Participants were predominantly female (68%), of mixed race/ethnicity, aged between 12 and 23 years (mean +/- SD age, 16.9 +/- 2.4), and from diverse socioeconomic backgrounds. SETTING: An adolescent health service in a suburban community-based teaching hospital. MAIN OUTCOME MEASURES: Adolescent smoking, alcohol and drug use, sexual practices, and weapon carrying. RESULTS: Adolescents with mentors were significantly less likely to participate in 4 of the 5 measured risk behaviors: ever carrying a weapon (odds ratio, 0.41; P< or =.01), illicit drug use in the past 30 days (odds ratio, 0.44; P< or =.01), smoking more than 5 cigarettes per day (odds ratio, 0.54; P< or =.05), and sex with more than 1 partner in the past 6 months (odds ratio, 0.56; P< or =.05). No significant difference was found with alcohol use (> or =3 drinks in the past 30 days). CONCLUSION: A strong positive relationship was found between adolescents having an adult mentor and decreased participation in 4 of the 5 risk behaviors evaluated.

Guidelines for adolescent health research: a position paper of the society for adolescent medicine.

Their ambiguous legal and ethical status has become a barrier to adolescents' appropriate involvement in research from which they may benefit and which is needed to improve adolescent health care and to inform health policy. Involvement of adolescents in research should be based on a scientific and empathetic understanding of their developing capabilities and a careful assessment of risks and benefits. The important role of parents and communities as protectors of adolescents should be respected and enhanced as we acknowledge and respect developing adolescent autonomy. These guidelines provide a framework to interpret the federal regulations for protection of human subjects in light of the unique legal, ethical, developmental, contextual, and racial issues that affect adolescents. The guidelines are designed to protect individual adolescent research subjects and to facilitate important youth research that would promote the health of adolescents.

The uterine cervix: diagnostic opportunities.

Sexually transmitted diseases, inflammatory conditions, and neoplasia occur all too often at the site of the uterine cervix. Multiple diagnostic options are available to clinicians ranging from simple inspection, to easily performed and widely accessible tests, to more complex laboratory procedures. Familiarity with and use of these methodologies by those providing health care for adolescents is likely to result in reduction of both the short- and long-term morbidity associated with these conditions.

Comparison of rapid diagnostic methodologies for Chlamydia and gonorrhea in an urban adolescent population: a pilot study.

PURPOSE: To compare a combination DNA probe test which detects both N. gonorrhoeae (GC) and C. trachomatis (CT) to the current culture methodologies among a population of female adolescents at an urban teaching center. In addition, the probe test for CT was compared to a direct immunofluorescence test. METHODS: All sexually active female adolescents between the ages of 13-21 years who sought care at an urban teaching center from June 1991 through November 1991 and who required testing for sexually transmitted diseases (STDs) were recruited for this study. RESULTS: The probe test was demonstrated to be 66.6% sensitive and 94.9% specific when compared to tissue culture for CT and 50% sensitive and 98.2% specific when compared to culture for GC. We found an overall prevalence of 23.5% for CT and 3.5% for GC. CONCLUSIONS: The two rapid diagnostic tests for CT evaluated in this study demonstrated similar sensitivities. However the probe test offers advantages in that it is easier to perform, skill at reading fluorescence is not required, and one specimen yields results for both CT and GC.

Follow-up evaluation of cervicovaginal human papillomavirus infection in adolescents.

We performed a second examination for human papillomavirus (HPV) DNA on 51 sexually experienced 13- to 21-year-old (mean = 17.8 years) female patients seen at an urban teaching hospital. Cervicovaginal lavages were performed 6 to 36 months apart (median = 13.3 months) to collect cells for HPV DNA detection and typing by Southern blot hybridization. At the first and second visits, 39.2% (20/51) and 25.5% (13/51) of patients, respectively, were infected with HPV. Collectively, 56.9% (29/51) of patients had at least one positive HPV test result. Although 7.8% (4/51) were infected with HPV at both visits, only one patient had infection with the same HPV type. These findings suggest that although HPV infection is a common sexually transmitted disease, genotype-specific HPV infection detected by Southern blot at two visits was rare.

Cervicovaginal human papillomavirus infection in suburban adolescents and young adults.

To investigate the prevalence rates of and risk factors for genital human papillomavirus (HPV) infection in white, middle-class adolescents, we obtained specimens for HPV from 107 patients undergoing pelvic examination at a suburban adolescent health service. Specimens were obtained by means of cervicovaginal lavage and were analyzed for HPV DNA by Southern blot analysis. The subjects' mean age was 18.5 (+/- 2.0 SD) years; 47% of the subjects were seen for contraception, 36% for possible pregnancy, 12% for a gynecologic complaint, and 5% for a general examination. We detected HPV in 32% of patients; HPV types included 6/11 (6%), 16 (3%), 18 (15%), 31 (3%), 42 (6%), 45 (18%), and 56 (6%). The DNA type was classified as uncharacterized in 47%, and 3% had more than one type. Univariate analysis revealed that patients found to have HPV were more likely to have more than two sexual partners, to have been sexually active for more than 2 years, to have had menarche before 12 years of age, and to have a history of sexually transmitted disease; logistic regression multivariate analysis demonstrated that number of partners and age at menarche were independent risk factors for HPV. These data indicate that HPV is common among sexually active teenagers regardless of ethnicity or socioeconomic status. The association of cervicovaginal HPV infection with sexual activity further supports the notion of the sexual transmission of this agent.

Sexually transmitted diseases in adolescents: update 1991.

Clinicians caring for sexually active adolescents are likely to be called on to diagnose and treat many of the STDs discussed in this article. A variety of other STDs not covered here also may be observed, including lymphogranuloma venereum, granuloma inguinale, molluscum contagiosum, scabies, pediculosis, and hepatitis A, B, and C. Some of the special issues related to gay and lesbian youth are discussed in the article by Drs Bidwell and Deisher (see "Adolescent Sexuality: Current Issues," pp 293-302). Nonetheless, it should be mentioned that the same STDs occur in homosexual youths as in their heterosexual counterparts. However, the prevalence rates for many STDs differ between the two groups, and some STDs are rarely seen in heterosexual males. These discrepancies may be explained by a number of determinants including anatomic and physiologic factors (eg, lesbian women have lower rates of STDs), differences in sexual practices (eg, genital-anal and oral-anal contact), and numbers of sexual partners, although this last factor may be less important in adolescents as compared with adult gay men. Discovery of one STD should always prompt a search for others because multiple concurrent infections is the rule rather than the exception. A serologic test for syphilis and a discussion of the potential for HIV infection (possibly testing for HIV as well) should take place at each new encounter for an STD. Some patients, including those with multiple partners, have an increased chance for acquisition of an STD. However, the reality is that any adolescent who has had sexual intercourse could have an STD.(ABSTRACT TRUNCATED AT 250 WORDS)

Storage artifact increases helper T lymphocytes and helper-to-suppressor T lymphocyte ratio to normal levels in a patient with acquired immune deficiency related complex.

An increase in both the helper/suppressor T lymphocyte ratio and the absolute number of helper T lymphocytes from subnormal to normal values was observed on overnight storage of a lymphocyte preparation from a patient with acquired immune deficiency related complex. Storage of lymphocyte preparations did not significantly alter the helper/suppressor ratio for four additional patients with acquired immune deficiency related complex but produced increases for one patient with Crohn's disease and two patients with sickle cell disease. Overnight storage of heparinized blood at room temperature did not alter the helper/suppressor ratio for one healthy volunteer and one patient with acquired immune deficiency related complex but produced increases for one patient with Crohn's disease and one patient with acute infectious mononucleosis, resulting in a change from a subnormal to a normal value in the latter patient. We suggest that physicians and laboratory directors consider storage artifacts when evaluating results of tests for absolute numbers of helper T lymphocytes or helper/suppressor T lymphocyte ratios performed on patients.

High prevalence rate of human papillomavirus infection and association with abnormal papanicolaou smears in sexually active adolescents.

Human papillomaviruses (HPVs) are associated with neoplastic and malignant lesions of the uterine cervix. Cervical neoplasia is associated with onset of sexual activity at an early age. Therefore, this study sought to define the prevalence rates of HPV infection and cytologic abnormalities in adolescents. Sexually active females 13 to 21 years of age undergoing routine cervical cytologic screening were evaluated in the adolescent clinic of an urban hospital. Cells collected by cervicovaginal lavage from 249 subjects were analyzed for HPV DNA by Southern blot hybridization with probes for HPV types 6/11, 16, and 18. The HPV DNA was detected in 95 (38.2%) of 249 patients. Teenagers between the ages of 13 and 18 years with multiple lifetime sexual partners were at higher risk for HPV infection (38/71 [54%]) compared with patients of the same age who had only a single partner (25/74 or [34%]). Twenty (8.3%) of 241 patients had abnormal Papanicolaou smears with atypia, koilocytosis, or low-grade cervical intraepithelial neoplasia. Cytologic abnormalities were detected in 16 (17%) of 94 adolescents with HPV present, but in only 4 (2.7%) of 147 of the uninfected patients. Thus, HPV emerged as a common pathogen in female adolescents, and infected patients are at increased risk for cervical epithelial abnormalities.

Vulvovaginitis and cervicitis.

Measures designed to reduce the incidence of cervicitis are those that make transmission of any STD less likely. Consistent and proper use of contraception, especially condoms, should be encouraged. Patients with a history of cervicitis or other STDs should be targeted for being at high risk and should have periodic screening tests to search for pathogens such as N. gonorrhoeae and C. trachomatis, even at times when they are asymptomatic. Other groups, including patients with multiple sexual partners, those with genitourinary symptoms, pregnant adolescents, and some adolescent clinic populations, also should be considered at increased risk and be monitored similarly. To be effective, encounters with adolescents around matters related to sexuality and STD must be done privately and with confidentiality assured. Special attention should be paid to the adolescent's family and cultural milieu, as well as to their level of psychosocial development, so that specific needs, fears, and misconceptions can be addressed. Cervicitis and other STDs are so common and have such important personal and public health implications that identification and effective treatment are of critical importance. The general tendency to be parsimonious when fitting together signs and symptoms into a medical diagnosis must be modified when dealing with STDs as multiple concomitant infections do occur routinely.