Anna-Barbara Moscicki

Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial.

BACKGROUND Effective vaccination against HPV 16 and HPV 18 to prevent cervical cancer will require a high level of sustained protection against infection and precancerous lesions. Our aim was to assess the long-term efficacy, immunogenicity, and safety of a bivalent HPV-16/18 L1 virus-like particle AS04 vaccine against incident and persistent infection with HPV 16 and HPV 18 and their associated cytological and histological outcomes. METHODS We did a follow-up study of our multicentre, double-blind, randomised, placebo-controlled trial reported in 2004. We included women who originally received all three doses of bivalent HPV-16/18 virus-like particle AS04 vaccine (0.5 mL; n=393) or placebo (n=383). We assessed HPV DNA, using cervical samples, and did yearly cervical cytology assessments. We also studied the long-term immunogenicity and safety of the vaccine. FINDINGS More than 98% seropositivity was maintained for HPV-16/18 antibodies during the extended follow-up phase. We noted significant vaccine efficacy against HPV-16 and HPV-18 endpoints: incident infection, 96.9% (95% CI 81.3-99.9); persistent infection: 6 month definition, 94.3 (63.2-99.9); 12 month definition, 100% (33.6-100). In a combined analysis of the initial efficacy and extended follow-up studies, vaccine efficacy of 100% (42.4-100) against cervical intraepithelial neoplasia (CIN) lesions associated with vaccine types. We noted broad protection against cytohistological outcomes beyond that anticipated for HPV 16/18 and protection against incident infection with HPV 45 and HPV 31. The vaccine has a good long-term safety profile. INTERPRETATION Up to 4.5 years, the HPV-16/18 L1 virus-like particle AS04 vaccine is highly immunogenic and safe, and induces a high degree of protection against HPV-16/18 infection and associated cervical lesions. There is also evidence of cross protection.

American Cancer Society Guideline for the Early Detection of Cervical Neoplasia and Cancer

An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical neoplasia and cancer, based on recommendations from a formal review and recent workshop, is presented. The new screening recommendations address when to begin screening, when screening may be discontinued, whether to screen women who have had a hysterectomy, appropriate screening intervals, and new screening technologies, including liquid‐based cytology and HPV DNA testing.

American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer

An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from 6 working groups, and a recent symposium cosponsored by the ACS, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology, which was attended by 25 organizations. The new screening recommendations address age‐appropriate screening strategies, including the use of cytology and high‐risk human papillomavirus (HPV) testing, follow‐up (eg, the management of screen positives and screening intervals for screen negatives) of women after screening, the age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16 and HPV18 infections. CA Cancer J Clin 2012.

The natural history of human papillomavirus infection as measured by repeated DNA testing in adolescent and young women

OBJECTIVES The objectives of this study were to describe the early natural history of human papillomavirus (HPV) infection by examining a cohort of young women positive for an HPV test and to define within this cohort (1) the probability of HPV regression, (2) the risk of having a squamous intraepithelial lesion, and (3) factors that were associated with HPV regression. STUDY DESIGN The study was a cohort analytic design. An inception cohort of 618 women positive for HPV participated. HPV testing, cytologic evaluation, and colposcopic evaluation were performed at 4-month intervals. HPV testing was characterized for two groups: low risk (five types rarely associated with cancers) and high risk (nine types most commonly associated with cancers). RESULTS Estimates provided by Kaplan-Meier curves showed that approximately 70% of women were found to have HPV regression by 24 months. Women with low-risk HPV type infections were more likely to show HPV regression than were women with high-risk HPV type infections (log rank test p = 0.002). The relative risk for the development of high-grade squamous intraepithelial lesion (HSIL) was 14.1 (95% confidence interval: 2.3, 84.5) for women with at least three positive tests for high-risk HPV preceding the development of the HSIL compared with that for women with negative tests for high-risk HPV. However, 88% of women with persistent positive HPV tests have not had HSIL to date. No factors associated with high-risk HPV type regression were identified except for a negative association with an incident history of vulvar condyloma (relative risk = 0.5 [95% confidence interval: 0.3 to 0.8]). CONCLUSION Most young women with a positive HPV test will become negative within a 24-month period. Persistent positive tests with oncogenic HPV types represented a significant risk for the development of HSIL. However, we found that most young women with persistent positive HPV tests did not have cytologically perceptible HSIL over a 2-year period. Factors thought to be associated with the development of HSIL were found not to be important in HPV regression.

American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer.

An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from 6 working groups, and a recent symposium cosponsored by the ACS, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology, which was attended by 25 organizations. The new screening recommendations address age-appropriate screening strategies, including the use of cytology and high-risk human papillomavirus (HPV) testing, follow-up (eg, the management of screen positives and screening intervals for screen negatives) of women after screening, the age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16 and HPV18 infections.

Regression of low-grade squamous intra-epithelial lesions in young women.

BACKGROUND The aim of this study was to assess the probability of low-grade squamous intra-epithelial lesion (LSIL) regression in young women, and to examine the factors associated with this regression. METHODS In a longitudinal study of human papilloma virus (HPV) infection, female adolescents aged 13-22 years were examined every 4 months by cytology, colposcopy, and HPV DNA status. Both prevalent and incident LSIL cases were included in the analysis, with regression defined as at least three consecutive normal Pap smears. FINDINGS Median follow-up time from baseline (defined as the time of first LSIL diagnosis) for the 187 women with LSIL was 61 months (IQR 34-80). Median time they had been sexually active at diagnosis was 3.2 years (2.6-6.5). Probability of regression for the entire cohort was 61% (95% CI 53-70) at 12 months and 91% (84-99) at 36 months of follow-up. No associations were found between LSIL regression and HPV status at baseline, sexual behaviour, contraceptive use, substance or cigarette use, incident sexually transmitted infection, or biopsy. Multivariate analysis showed that only HPV status at the current visit was associated with rate of regression, whether infection was caused by one or more viral types (relative hazard=0.3 [95% CI 0.21-0.42], and 0.14 [0.08-0.25], respectively). INTERPRETATION The high rate of regression recorded in this study lends support to observation by cytology in the management of LSIL in female adolescents. Negative HPV status was associated with regression, suggesting that HPV testing could be helpful in monitoring LSIL.

American Cancer Society Guideline for Human Papillomavirus (HPV) Vaccine Use to Prevent Cervical Cancer and Its Precursors

The American Cancer Society (ACS) has developed guidelines for the use of the prophylactic human papillomavirus (HPV) vaccine for the prevention of cervical intraepithelial neoplasia and cervical cancer. These recommendations are based on a formal review of the available evidence. They address the use of prophylactic HPV vaccines, including who should be vaccinated and at what age, as well as a summary of policy and implementation issues. Implications for screening are also discussed.

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).

External genital warts: diagnosis, treatment, and prevention.

External genital warts (EGWs) are visible warts that occur in the perigenital and perianal regions. They are due primarily to non-oncogenic human papillomavirus (HPV) types, usually types 6 and 11. Physical examination assisted by bright light and magnification is the recommended approach for primary diagnosis. Biopsy is indicated when EGWs are fixed to underlying structures or discolored or when standard therapies are not effective. Recurrences are common, and there is no single treatment that is superior to others. Among women with atypical squamous cells, molecular HPV testing may be useful in determining who should be referred for colposcopy. Condoms may provide some protection against HPV-related diseases and thus are recommended in new sexual relationships and when partnerships are not mutually monogamous. Because the efficacy of cesarean section in preventing vertical transmission of HPV infection from women with EGWs to their progeny has not been proved, it is not recommended.

American cancer society, american society for colposcopy and cervical pathology, and american society for clinical pathology screening guidelines for the prevention and early detection of cervical cancer

Abstract An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from six working groups, and a recent symposium co-sponsored by the ACS, American Society for Colposcopy and Cervical Pathology (ASCCP), and American Society for Clinical Pathology (ASCP), which was attended by 25 organizations. The new screening recommendations address age-appropriate screening strategies, including the use of cytology and high-risk human papillomavirus (HPV) testing, follow-up (e.g., management of screen positives and screening interval for screen negatives) of women after screening, age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16/18 infections.