{'fraction_non_alphanumeric': 0.026626583637534895, 'fraction_numerical': 0.02791496671677045, 'mean_word_length': 5.010322580645162, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 1, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 3, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Human papillomavirus vaccine should be given before sexual debut for maximum benefit.

In this issue of the Journal, the Mercksponsored FUTURE II Study Group presents an analysis of the prophylactic efficacy of its quadrivalent human papillomavirus (HPV) vaccine (Gardasil) among a subgroup of 4722 women from the FUTURE I and FUTURE II studies with evidence of current or past infection with at least 1 HPV vaccine type (6, 11, 16, or 18) at the time of vaccination [1]. It reports an efficacy of 100% against cervical intraepithial neoplasia 2/3 or adenocarcinoma in situ and of 94% against vulvar or vaginal HPV-related lesions among women who, at the time of vaccination, were seropositive or polymerase chain reaction positive for 1 of the HPV vaccine types but were naive for the type detected in histological sections of the lesion defined as an outcome. This report follows closely the publication of the main findings from the FUTURE I and FUTURE II trials of 17,622 women, which also reported very high prophylactic efficacy against these same conditions [2, 3]. Although reassuring, the results presented are not unexpected, given that the nearcomplete protection observed for the entire FUTURE I/II cohort by definition requires equally high protection within all subgroups, including the subgroup of exposed women evaluated in the present report. The results observed are also consistent with the biological assumption that the prophylactic efficacy against an HPV type for which a woman is naive should not vary on the basis of present or past infection with other HPV types. The results reported by the FUTURE II Study Group [1] are from according-toprotocol (ATP) efficacy analyses that evaluate only the prophylactic effect of vaccination rather than the overall impact of vaccination on disease burden among women already infected with 1 or more HPV types. Although such restricted ATP analyses are necessary and important for licensure, they are incomplete for subsequent discussions and for the formulation of vaccine implementation guidelines. The development of evidence-based public health guidelines require wellformulated intent-to-treat (ITT) analyses to determine overall effectiveness at the population level, including all-HPV-type outcomes. It is therefore an important limitation of the analysis presented that no data on the absolute effectiveness of vaccinating previously exposed or infected women are presented in the report by the FUTURE II Study Group. In its report, the FUTURE II Study Group concludes that universal catch-up vaccination of young adult women is desirable because, even among women with evidence of previous or current infection with 1 or more HPV vaccine types, residual benefit remains from the prophylactic effect of the vaccine against the types to which these women are not known to be exposed. This conclusion does not take into account the decline in the proportion of naive individuals remaining in each successive age cohort; as women age and become increasingly exposed to HPV, the pool of naive women is reduced, thereby reducing the marginal benefit of vaccination. We disagree with the authors’ conclusions leading to the generalization that residual benefit among older women, no matter how small, justifies universal vaccination of women years into their sexual life. Some have gone so far as to suggest that the vaccine should be offered to women into their 40s and 50s. Although universal vaccination of women into their adult life might be reasonable for an inexpensive and totally risk-free product, this is not the case for the currently available vaccine—it is not inexpensive, nor has it Received 19 July 2007; accepted 19 July 2007; electronically published 31 October 2007. Potential conflicts of interest: A.H. and R.H. are the principal investigators of a US National Cancer Institute (NCI)– sponsored and Costa Rica Ministry of Health–supported clinical trial in Costa Rica to evaluate the efficacy and effectiveness of a bivalent HPV-16 and -18 vaccine manufactured by GlaxoSmithKline Biologicals. The trial is funded by the US NCI (N01-CP-11005) with support from the National Institutes of Health Office for Research on Women’s Health. Reprints or correspondence: Dr. Allan Hildesheim, National Institutes of Health, National Cancer Institute, Div. of Cancer Epidemiology, 6120 Executive Blvd., Rm. 7062, Rockville, MD 20852 (hildesha@epndce.nci.nih.gov). The Journal of Infectious Diseases 2007; 196:1431–2 © 2007 by the Infectious Diseases Society of America. All rights reserved. 0022-1899/2007/19610-0001$15.00 DOI: 10.1086/522869 E D I T O R I A L C O M M E N T A R Y