Nine-valent HPV vaccine efficacy against related diseases and definitive therapy: comparison with historic placebo population.

OBJECTIVE: Nine-valent human papillomavirus (9vHPV) vaccine efficacy against disease and cervical surgeries related to all nine vaccine components was assessed compared with a historic placebo population. This was not assessed in the 9vHPV vaccine efficacy trial since the trial was quadrivalent HPV (qHPV) vaccine-controlled, efficacy was measured for the five HPV types covered only by 9vHPV vaccine (HPV31/33/45/52/58), but not the four types covered by both vaccines (HPV6/11/16/18). METHODS: Three international, randomized, double-blind studies were conducted using the same methodology. In the 9vHPV vaccine study (NCT00543543), 7106 and 7109 women received 9vHPV or qHPV vaccine, respectively. In the historic qHPV vaccine studies (FUTURE I [NCT00092521] and II [NCT00092534]), 8810 and 8812 women received qHPV vaccine or placebo, respectively, based on the same eligibility criteria. Cervical cytological testing was performed regularly. Biopsy or definitive therapy specimens were assessed for HPV DNA. RESULTS: Among women negative for 14 HPV types prior to vaccination, incidence of high-grade cervical disease (9vHPV, n = 2 cases; placebo, n = 141 cases) and cervical surgery (9vHPV, n = 3 cases; placebo, n = 170 cases) related to the nine HPV types was reduced by 98.2% (95% confidence interval [CI], 93.6-99.7) and 97.8% (95% CI, 93.4-99.4), respectively. The 9vHPV vaccine did not prevent disease related to vaccine HPV types detected at baseline, but significantly reduced cervical, vulvar, and vaginal diseases related to other vaccine HPV types. CONCLUSIONS: Effective implementation of the 9vHPV vaccine may substantially reduce the burden of HPV-related diseases and related medical procedures. TRIAL REGISTRATIONS: clinicaltrials.gov: NCT00543543, NCT00092521, NCT00092534.

Human papillomavirus type specific risk of progression and remission during long-term follow-up of equivocal and low-grade HPV-positive cervical smears.

The prevalence of clinically relevant HPV types and their specific risk for progression and regression in women with atypical squamous cells of uncertain significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) were studied in a routine screening population. A 4-year cohort of women (n = 820) with ASCUS/LSIL and a positive HPV test in triage were followed for 6-9 years. The progression risks for CIN2+/CIN3+ were determined for single (71.2%) and multiple HPV infections (28.8%). The CIN2+ progression risk for all HPV 16, all HPV 35, single HPV 16 and single HPV 35 infections were 65.3% (95% CI: 59.6-71.0), 64.4% (95% CI: 50.4-78.4), 63.8% (95% CI: 56.2-71.4) and 73.7% (95% CI: 53.9-93.5), respectively. Based on CIN2+ progression risks four main groups were defined; the HPV 16 group, the HPV 31/33/35 group, the HPV 18/45/51/52 group and the HPV 39/56/58/59/66/68 group with progression risks of 65.3% (95% CI: 59.6-71.0), 62.1% (95% CI: 54.8-69.4), 52.6 (95% CI: 45.9-59.3) and 39.5 (95% CI: 33.0-46.0), respectively. In multivariate analyses, women in the age group 40-49 years had an increased risk of CIN2+ progression. As for CIN3+, HPV 16 had a higher progression risk than other HPV risk groups (p < 0.05). In multiple infections only HPV 16 had a significant additive CIN3+ progression risk (p < 0.05) as compared to other HPV risk groups. In summary, HPV types 16 and 35, including the HPV risk group 31/33/35, had a similar CIN2+ progression risk, but only HPV 16 had a higher risk for CIN3+ progression.

Final efficacy, immunogenicity, and safety analyses of a nine-valent human papillomavirus vaccine in women aged 16-26 years: a randomised, double-blind trial.

BACKGROUND: Primary analyses of a study in young women aged 16-26 years showed efficacy of the nine-valent human papillomavirus (9vHPV; HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58) vaccine against infections and disease related to HPV 31, 33, 45, 52, and 58, and non-inferior HPV 6, 11, 16, and 18 antibody responses when compared with quadrivalent HPV (qHPV; HPV 6, 11, 16, and 18) vaccine. We aimed to report efficacy of the 9vHPV vaccine for up to 6 years following first administration and antibody responses over 5 years. METHODS: We undertook this randomised, double-blind, efficacy, immunogenicity, and safety study of the 9vHPV vaccine study at 105 study sites in 18 countries. Women aged 16-26 years old who were healthy, with no history of abnormal cervical cytology, no previous abnormal cervical biopsy results, and no more than four lifetime sexual partners were randomly assigned (1:1) by central randomisation and block sizes of 2 and 2 to receive three intramuscular injections over 6 months of 9vHPV or qHPV (control) vaccine. All participants, study investigators, and study site personnel, laboratory staff, members of the sponsor's study team, and members of the adjudication pathology panel were masked to vaccination groups. The primary outcomes were incidence of high-grade cervical disease (cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, invasive cervical carcinoma), vulvar disease (vulvar intraepithelial neoplasia grade 2/3, vulvar cancer), and vaginal disease (vaginal intraepithelial neoplasia grade 2/3, vaginal cancer) related to HPV 31, 33, 45, 52, and 58 and non-inferiority (excluding a decrease of 1·5 times) of anti-HPV 6, 11, 16, and 18 geometric mean titres (GMT). Tissue samples were adjudicated for histopathology diagnosis and tested for HPV DNA. Serum antibody responses were assessed by competitive Luminex immunoassay. The primary evaluation of efficacy was a superiority analysis in the per-protocol efficacy population, supportive efficacy was analysed in the modified intention-to-treat population, and the primary evaluation of immunogenicity was a non-inferiority analysis. The trial is registered with ClinicalTrials.gov, number NCT00543543. FINDINGS: Between Sept 26, 2007, and Dec 18, 2009, we recruited and randomly assigned 14 215 participants to receive 9vHPV (n=7106) or qHPV (n=7109) vaccine. In the per-protocol population, the incidence of high-grade cervical, vulvar and vaginal disease related to HPV 31, 33, 45, 52, and 58 was 0·5 cases per 10 000 person-years in the 9vHPV and 19·0 cases per 10 000 person-years in the qHPV groups, representing 97·4% efficacy (95% CI 85·0-99·9). HPV 6, 11, 16, and 18 GMTs were non-inferior in the 9vHPV versus qHPV group from month 1 to 3 years after vaccination. No clinically meaningful differences in serious adverse events were noted between the study groups. 11 participants died during the study follow-up period (six in the 9vHPV vaccine group and five in the qHPV vaccine group); none of the deaths were considered vaccine-related. INTERPRETATION: The 9vHPV vaccine prevents infection, cytological abnormalities, high-grade lesions, and cervical procedures related to HPV 31, 33, 45, 52, and 58. Both the 9vHPV vaccine and qHPV vaccine had a similar immunogenicity profile with respect to HPV 6, 11, 16, and 18. Vaccine efficacy was sustained for up to 6 years. The 9vHPV vaccine could potentially provide broader coverage and prevent 90% of cervical cancer cases worldwide. FUNDING: Merck & Co, Inc.

A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women.

BACKGROUND: The investigational 9-valent viruslike particle vaccine against human papillomavirus (HPV) includes the HPV types in the quadrivalent HPV (qHPV) vaccine (6, 11, 16, and 18) and five additional oncogenic types (31, 33, 45, 52, and 58). Here we present the results of a study of the efficacy and immunogenicity of the 9vHPV vaccine in women 16 to 26 years of age. METHODS: We performed a randomized, international, double-blind, phase 2b-3 study of the 9vHPV vaccine in 14,215 women. Participants received the 9vHPV vaccine or the qHPV vaccine in a series of three intramuscular injections on day 1 and at months 2 and 6. Serum was collected for analysis of antibody responses. Swabs of labial, vulvar, perineal, perianal, endocervical, and ectocervical tissue were obtained and used for HPV DNA testing, and liquid-based cytologic testing (Papanicolaou testing) was performed regularly. Tissue obtained by means of biopsy or as part of definitive therapy (including a loop electrosurgical excision procedure and conization) was tested for HPV. RESULTS: The rate of high-grade cervical, vulvar, or vaginal disease irrespective of HPV type (i.e., disease caused by HPV types included in the 9vHPV vaccine and those not included) in the modified intention-to-treat population (which included participants with and those without prevalent infection or disease) was 14.0 per 1000 person-years in both vaccine groups. The rate of high-grade cervical, vulvar, or vaginal disease related to HPV-31, 33, 45, 52, and 58 in a prespecified per-protocol efficacy population (susceptible population) was 0.1 per 1000 person-years in the 9vHPV group and 1.6 per 1000 person-years in the qHPV group (efficacy of the 9vHPV vaccine, 96.7%; 95% confidence interval, 80.9 to 99.8). Antibody responses to HPV-6, 11, 16, and 18 were noninferior to those generated by the qHPV vaccine. Adverse events related to injection site were more common in the 9vHPV group than in the qHPV group. CONCLUSIONS: The 9vHPV vaccine prevented infection and disease related to HPV-31, 33, 45, 52, and 58 in a susceptible population and generated an antibody response to HPV-6, 11, 16, and 18 that was noninferior to that generated by the qHPV vaccine. The 9vHPV vaccine did not prevent infection and disease related to HPV types beyond the nine types covered by the vaccine. (Funded by Merck; ClinicalTrials.gov number, NCT00543543).

Medical abortions performed by specialists in private practice. / Medikamentell abort hos avtalespesialist.

BAKGRUNN: I Norge utføres abort kun i offentlige sykehus. I 2010 besluttet Helse- og omsorgsdepartementet å iverksette et toårig prøveprosjekt som ga avtalespesialister i fødselshjelp og kvinnesykdommer adgang til å tilby medikamentell abort før utgangen av 9. svangerskapsuke. Prøveprosjektet ble igangsatt 1.3.2015 og varte til 31.3.2017. I denne artikkelen presenterer vi de første erfaringene, herunder hvordan behandlingstilbudet ble mottatt av kvinnene. MATERIALE OG METODE: Gravide med en svangerskapsvarighet < 63 dager ultrasonografisk vurdert, som oppsøkte avtalespesialist for medikamentell abort, ble fortløpende inkludert i prosjektet (n = 476). Kvinnene inntok 200 mg mifepriston peroralt på legekontoret, 36-48 timer senere satte de selv 800 µg misoprostol vaginalt hjemme. Informasjon ble innhentet ved spørreskjema på den første konsultasjonen, under aborten og ved etterkontrollen 2-4 uker etter aborten. RESULTATER: Under aborten rapporterte 66 % (296/450) moderat eller sterk smerte og 79 % (358/451) moderat eller sterk blødning. De fleste opplevde det som trygt å være hjemme. 96 % (390/406) ville valgt medikamentell abort hos avtalespesialist ved en eventuell senere abort, og 97 % (392/405) ville anbefalt behandlingstilbudet til andre i samme situasjon. FORTOLKNING: Kvinnene i studien opplevde abortbehandling hos avtalespesialist som trygt. Tilbudet gir større valgfrihet til gravide som ønsker abort, og pasientene er tilfredse.

Use of hormone replacement therapy after risk-reducing salpingo-oophorectomy.

INTRODUCTION: After premenopausal risk-reducing salpingo-oophorectomy (RRSO) to prevent ovarian cancer, the non-cancer-related morbidity and mortality may be increased if sex hormones are not replaced. Several guidelines recommend systemic hormone replacement therapy (HRT) to these women until the expected age of menopause. We aimed to study the use of HRT after RRSO. MATERIAL AND METHODS: Participants were 324 women after RRSO and 11 160 postmenopausal controls. A subsample of 950 controls had undergone bilateral salpingo-oophorectomy (BSO). All participants completed the same questionnaire regarding HRT use. We compared HRT use in the RRSO group with the BSO controls using logistic regression. RESULTS: Among the women aged ≤52 years without a history of breast cancer, 51.7% of the RRSO group and 48.7% of the BSO controls reported current use of systemic HRT (odds ratio 1.13, 95% confidence interval 0.72-1.76). Among the HRT users, systemic estrogen was used by 35.1% and 58.7% in the RRSO and BSO control groups, respectively (p = 0.001). Among the women aged >52 years, 16.8% of the RRSO group and 38.4% of the BSO controls (p < 0.001) used systemic HRT. CONCLUSIONS: Among the RRSO women and BSO controls ≤52 years old without a history of breast cancer, relatively few were current users. If there are no contraindications, these women would benefit from systemic HRT. Additionally, almost 40% of the BSO controls >52 years used systemic HRT. Doctors should be aware of this practice and prescribe systemic HRT when indicated.

Immunogenicity of the 9-Valent HPV Vaccine Using 2-Dose Regimens in Girls and Boys vs a 3-Dose Regimen in Women.

Importance: Human papillomavirus (HPV) infections cause anogenital cancers and warts. The 9-valent HPV vaccine provides protection against 7 high-risk types of HPV responsible for 90% of cervical cancers and 2 other HPV types accounting for 90% of genital warts. Objective: To determine whether HPV type-specific antibody responses would be noninferior among girls and boys aged 9 to 14 years after receiving 2 doses of the 9-valent HPV vaccine compared with adolescent girls and young women aged 16 to 26 years receiving 3 doses. Design, Setting, and Participants: Open-label, noninferiority, immunogenicity trial conducted at 52 ambulatory care sites in 15 countries. The study was initiated on December 16, 2013, with the last participant visit for this report on June 19, 2015. Five cohorts were enrolled: (1) girls aged 9 to 14 years to receive 2 doses 6 months apart (n = 301); (2) boys aged 9 to 14 years to receive 2 doses 6 months apart (n = 301); (3) girls and boys aged 9 to 14 years to receive 2 doses 12 months apart (n = 301); (4) girls aged 9 to 14 years to receive 3 doses over 6 months (n = 301); and (5) a control group of adolescent girls and young women aged 16 to 26 years to receive 3 doses over 6 months (n = 314). Interventions: Two doses of the 9-valent HPV vaccine administered 6 or 12 months apart or 3 doses administered over 6 months. Main Outcomes and Measures: The primary end point was prespecified as the antibody response against each HPV type assessed 1 month after the last dose using a competitive immunoassay. Each of the three 2-dose regimens was compared with the standard 3-dose schedule in adolescent girls and young women using a noninferiority margin of 0.67 for the ratio of the antibody geometric mean titers. Results: Of the 1518 participants (753 girls [mean age, 11.4 years]; 451 boys [mean age, 11.5 years]; and 314 adolescent girls and young women [mean age, 21.0 years]), 1474 completed the study and data from 1377 were analyzed. At 4 weeks after the last dose, HPV antibody responses in girls and boys given 2 doses were noninferior to HPV antibody responses in adolescent girls and young women given 3 doses (P < .001 for each HPV type). Compared with adolescent girls and young women who received 3 doses over 6 months, the 1-sided 97.5% CIs for the ratio of HPV antibody geometric mean titers at 1 month after the last dose across the 9 HPV subtypes ranged from 1.36 to ∞ to 2.50 to ∞ for girls who received 2 doses 6 months apart; from 1.37 to ∞ to 2.55 to ∞ for boys who received 2 doses 6 months apart; and from 1.61 to ∞ to 5.36 to ∞ for girls and boys who received 2 doses 12 months apart. Conclusions and Relevance: Among girls and boys aged 9 to 14 years receiving 2-dose regimens of a 9-valent HPV vaccine separated by 6 or 12 months, immunogenicity 4 weeks after the last dose was noninferior to a 3-dose regimen in a cohort of adolescent girls and young women. Further research is needed to assess persistence of antibody responses and effects on clinical outcomes. Trial Registration: clinicaltrials.gov Identifier: NCT01984697.

Establishment of treatment methods without critical reflection. / Etablering av behandlingsmetoder uten kritisk refleksjon.

New treatment methods are sometimes introduced with no knowledge of whether the method yields better results than established treatment or how frequently complications arise.

A randomized study of hexaminolevulinate photodynamic therapy in patients with cervical intraepithelial neoplasia 1/2.

OBJECTIVE: The objective of the study was to investigate the efficacy and safety of hexaminolevulinate (HAL) photodynamic therapy (PDT), a novel therapy for women with cervical intraepithelial neoplasia (CIN)1/2, to define the appropriate population and endpoints for a phase 3 program. STUDY DESIGN: This was a double-blind, randomized, placebo-controlled, dose-finding study that included a total of 262 women with biopsy-confirmed CIN 1/2 based on local pathology. Patients received 1 or 2 topical treatments of HAL hydrochloride 0.2%, 1%, 5%, and placebo ointment and were evaluated for response after 3-6 months based on biopsy, Papanicolaou test, and oncogenic human papillomavirus (HPV) test. All efficacy analyses were performed on blinded central histology review to avoid interreader variability. Adverse events, blood biochemistry, and vital signs were assessed after 3 months. RESULTS: There were no statistically significant differences between placebo and either the CIN 1 or combined CIN 1/2 populations. A clear dose effect with a statistically significant response in the HAL 5% group of 95% (18/19 patients) compared to 57% (12/21 patients) in the placebo group (P < .001) was observed at 3 months in women with CIN 2, including an encouraging 83% (5/6 patients) clearance of HPV 16/18 compared to 33% (2/6 patients) in the placebo group at 6 months. The treatment was easy to use and well accepted by patients and gynecologists. Only local self-limiting adverse reactions including discharge, discomfort, and spotting were reported. CONCLUSION: HAL PDT is a novel therapy that shows promise in the treatment of CIN 2 including clearance of oncogenic HPV, but not of CIN 1. The positive risk/benefit balance makes HAL PDT a tissue-preserving alternative in women of childbearing age who wish to preserve the cervix. Confirmatory studies are planned.

Medical abortion with mifepristone and home administration of misoprostol up to 63 days' gestation.

OBJECTIVE: To evaluate the acceptability and efficacy of medical abortion at home up to 63 days' gestation without limits on travel distance to a registered institution. DESIGN: Observational prospective study. SETTING: Haukeland University Hospital between May 2006 and May 2009. POPULATION: A total of 1018 women requesting abortion before 63 days' gestation who chose medical termination with mifepristone and home administration of misoprostol. METHODS: The women took 200 mg mifepristone under nurse supervision and self-administered 800 µg misoprostol vaginally 36-48 h later at home. All were contacted by phone for follow-up and assessment of bleeding, pain and acceptability. MAIN OUTCOME MEASURES: Evacuation rate, pain, bleeding, acceptability, influence of distance on treatment. RESULTS: Median gestational age was 50 (range 35-63) days and 70 (7.1%) of the women lived more than 60 min travel from the clinic. The rate of completed abortion was 93.6% and surgical evacuation was performed in 50 (4.9%) cases. Two women requested treatment on the day of misoprostol use. Moderate to strong pain was experienced by 68.4%, and 74.7% reported moderate to heavy bleeding. Parous women experienced less pain than nulliparous women (odds ratio 0.27; 95% confidence interval 0.19-0.34). In all, 95.1% of the women were satisfied with staying at home. Travel distance did not influence treatment outcome variables. CONCLUSIONS: In our experience, home administration of misoprostol is an effective and acceptable method for abortion up to 63 days of gestation and women should be eligible for this treatment option regardless of their travel distance from hospital.

[Is it possible to obtain reliable information about the long-term effects of induced abortion?]. / Er det mulig å få pålitelig kunnskap om psykiske senvirkninger etter provosert abort?

BACKGROUND: The psychological long-term effects of an induced abortion are the subject of constant debate, but the scientific basis of experience is limited and by no means unambiguous. We wanted to study how a random selection of women felt about pre-agreed follow-up studies after an induced abortion. MATERIAL AND METHOD: All abortion patients who attended the Department of Obstetrics and Gynaecology at Haukeland University Hospital during a three-month period received a questionnaire. They were asked if they would be willing to be contacted in writing with questions about long-term effects 1-2 years and 5-10 years after the intervention, and to give reasons for their decisions by setting crosses in the multiple choice responses that were listed. RESULTS: During the period of the study, 300 abortions were carried out at the department. Questionnaires were distributed to 227 of these patients, and 181 (80 %) of them were included. 43 % of the women in the study agreed to take part in a questionnaire survey concerning the long-term effects, if any, of induced abortion 1-2 years after the intervention, and 35 % 5-10 years afterwards. INTERPRETATION: It appears that it may be difficult to study the psychological long-term effects of induced abortion by means of questionnaire surveys. Our results indicate that the percentage of participants in long-term studies would be too low, and hence not representative of the group as a whole.

Randomized Implementation of a Primary Human Papillomavirus Testing-based Cervical Cancer Screening Protocol for Women 34 to 69 Years in Norway.

BACKGROUND: Cervical cancer screening programs are facing a programmatic shift where screening protocol based on human papillomavirus testing (HPV-Screening protocol) is replacing the liquid-based cytology (LBC-Screening protocol). For safe technology transfer within the nationwide screening programme in Norway, HPV-Screening protocol was implemented randomized to compare the real-world effectiveness of HPV-Screening protocol and LBC-Screening protocol at the first screening round. METHODS: Among 302,295 women ages 34 to 69 years scheduled to attend screening from February 2015 to June 2017, 157,447 attended. A total of 77,207 were randomly allocated to the HPV-Screening protocol and 80,240 were allocated to the LBC-Screening protocol. All women were followed up for 18 months. RESULTS: The HPV-Screening protocol resulted in a relative increase of 60% in the detection of cervical intraepithelial neoplasia (CIN) grade 2 or worse [risk ratio (RR) = 1.6, 95% confidence interval (CI) = 1.5-1.7], 40% in CIN grade 3 or worse (RR = 1.4, 95% CI = 1.3-1.6), 40% in cancer (RR = 1.4, 95% CI = 1.0-2.1), and 60% in colposcopy referrals (RR = 1.6, 95% CI = 1.5-1.6) compared with LBC-Screening. The performance of both protocols was age dependent, being more effective in women ages under 50 years. CONCLUSIONS: The HPV-Screening protocol was well accepted by women in Norway and detected more CIN2, CIN3, and cancers compared with the LBC-Screening protocol. IMPACT: A randomized implementation of the HPV-Screening protocol with real-world assessment enabled a gradual, quality assured, and safe technology transition. HPV-based screening protocol may further be improved by using HPV genotyping and age-specific referral algorithms.

Adenocarcinoma in situ and associated human papillomavirus type distribution observed in two clinical trials of a quadrivalent human papillomavirus vaccine.

The primary objective of this report is to describe the detection of adenocarcinoma in situ (AIS) and associated human papillomavirus (HPV) type distribution that was observed in the context of two phase 3 clinical trials of a quadrivalent HPV6/11/16/18 vaccine. In this intention-to-treat analysis, we include all women who had at least one follow-up visit postenrollment. Healthy women (17,622) aged 15-26 with no history of HPV disease and a lifetime number of less than five sex partners (average follow-up of 3.6 years) were randomized (1:1) to receive vaccine or placebo at day 1, months 2, and 6. Women underwent colposcopy and biopsy according to a Papanicolaou triage algorithm. All tissue specimens were tested for 14 HPV types and were adjudicated by a pathology panel. During the trials, 22 women were diagnosed with AIS (six vaccine and 16 placebo). There were 25 AIS lesions in total, with HPV16/18 present in 96% (24 of 25 with 15 of 25 as single infections). Only two of 22 women had concomitant cytology results suggesting glandular abnormality. Colposcopic impressions (25 total) were either negative or indicated squamous lesions only. Of women with AIS, all six in the vaccine cohort and seven of 16 in the placebo cohort were infected at baseline with the same HPV type that was detected in the AIS lesion. Concurrent squamous lesions were detected in 20 of these 22 women. In summary, our findings show that AIS evades colposcopic and cervical cytologic detection. As most AIS lesions were HPV16/18-related, prophylactic HPV vaccination should reduce the incidence of invasive adenocarcinoma.

[Mass examination for gynecological cancer--status and future]. / Masseundersøkelser mot gynekologisk kreft--status og fremtid.

BACKGROUND: In Norway, mass examination for cervical cancer was started in 1995 with the goal to reduce incidence and mortality through rational use of resources. This has been successful. We wished to assess the knowledge base for this practice, as well as that on usefulness of mass examination for ovarian cancer and uterine body cancer. MATERIAL AND METHOD: This article is based on literature identified through a non-systematic search in PubMed. RESULTS: Despite knowledge of several risk factors for uterine body cancer, there is not sufficient evidence to support mass examination for this condition. Within a few years it will become clear whether large ongoing studies provide sufficient evidence to recommend screening for ovarian cancer. The effect of mass examination for cervical cancer is well documented. INTERPRETATION: Cervical cancer is the only gynecological condition with an established mass examination program. This program must be adapted to new methods and the population's vaccine status in the coming years. There is not sufficient documentation on ovarian cancer or uterine body cancer to support mass examination, but this may change during a few years.

Evaluation of quadrivalent HPV 6/11/16/18 vaccine efficacy against cervical and anogenital disease in subjects with serological evidence of prior vaccine type HPV infection.

OBJECTIVE: In the quadrivalent (types 6/11/16/18) HPV vaccine (GARDASIL/SILGARD) clinical program, 73% of women aged 16-26 were naïve to all vaccine HPV types. In these women, prophylactic administration of the vaccine was highly effective in preventing HPV 6/11/16/18-related cervical disease. Of the remaining women, 15% of had evidence of past infection with one or more vaccine HPV types (seropositive and DNA negative) at the time of enrollment. Here we present an analysis in this group of women to determine the efficacy of the HPV 6/11/16/18 vaccine against new cervical and external anogenital disease related to the same vaccine HPV type which had previously been cleared. Vaccine tolerability in this previously infected population was also assessed. METHODS: 18,174 women were enrolled into 3 clinical studies. The data presented comprise a subset of these subjects (n = 2,617) who were HPV seropositive and DNA negative at enrollment (for >or=1 vaccine type). In each study, subjects were randomized in a 1:1 ratio to receive HPV 6/11/16/18 vaccine or placebo at day 1, month 2 and month 6 (without knowledge of baseline HPV status). Procedures performed for efficacy data evaluation included detailed genital examination, Pap testing, and collection of cervicovaginal and external genital specimens. Analyses of efficacy were carried out in a population stratified by HPV serology and HPV DNA status at enrollment. RESULTS: Subjects were followed for an average of 40 months. Seven subjects in the placebo group developed cervical disease, and eight subjects developed external genital disease related to a vaccine HPV type they had previously encountered. No subject receiving HPV 6/11/16/18 vaccine developed disease to a vaccine HPV type to which they were seropositive and DNA negative at enrolment. CONCLUSIONS: These results suggest that natural HPV infection-elicited antibodies may not provide complete protection over time, however the immune response to the HPV 6/11/16/18 vaccine appears to prevent reinfection or reactivation of disease with vaccine HPV types. Vaccine-related adverse experiences were higher among subjects receiving vaccine, mostly due to increased injection site adverse experiences.