A shorter interval between menarche and first sexual intercourse is associated with increased risk of high-grade cervical disease
- Correspondence to: Dr Jennifer S Smith
Department of Epidemiology, UNC Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, 2103 McGavran-Greenberg, 135 Dauer Drive, Campus Box 7435, Chapel Hill 27599, USA;
Commentary on: Ruiz AM, Ruiz JE, Gavilanes AV, et al. for the FUTURE I and II Study Group. Proximity of first sexual intercourse to menarche and risk of high-grade cervical disease. J Infect Dis 2012;206:1887–96.
Implications for practice and research
Female adolescents with a shorter duration between the age of menarche and first sexual intercourse are at an increased risk of high-grade cervical disease.
Clinical counselling should include clear recommendations to obtain human papillomavirus (HPV) vaccination well before first intercourse to reduce the future risk of high-grade cervical lesions among sexually naïve female adolescents.
Ruiz and colleagues present associations between a shorter interval between menarche and first sexual intercourse on subsequent risk of high-grade cervical intraepithelial neoplasia (CIN-2+) or adenocarcinoma in situ among young women (16–23 years), in phase III randomised controlled trials (RCTs) in Colombia and Finland. Carcinogenic HPV infection is the main cause of invasive cervical cancer (ICC). Given that HPV infections are common but ICC is relatively rare, other cofactors likely act in conjunction with HPV to increase a woman's risk of ICC and associated high-grade cervical lesions1 Data examining the risk of high-grade cervical lesions in different time intervals between a woman's age at menarche and her age of first sexual intercourse are needed. If a window of susceptibility between menarche and age at first intercourse is identified, counselling messages can be developed to optimise prevention efforts.
Two well conducted RCTs of quadrivalent HPV vaccination in Colombia and Finland from 2001 to 2003 provided a unique opportunity for the authors to examine young women's self-reported intervals between age at menarche and age of first intercourse on the risk of high-grade cervical lesions over a 4-year study follow-up period. Of 17 622 enrolled participants, a relatively small number of female adolescents (ie, 1009 and 1012 from Colombia and Finland, respectively) provided data on both age at menarche and age at first intercourse. Although not population-based, pre-existing data collected within the RCTs provided reliable outcome data on HPV infection status using sensitive PCR and on the prevalence of CIN-2+ or adenocarcinoma in situ, with a strict protocol of referring women with abnormal cytology to colposcopy and histology upon indication.
The risk of CIN-2+ or adenocarcinoma in situ was higher among sexually naïve female adolescents who reported shorter intervals between menarche and first sexual encounter, and lower among those who reported oral contraceptive use. Age at menarche was not associated with HPV positivity or abnormal cytology status at the baseline visit, and was similar in Colombia and Finland. Female adolescents were at a higher risk of HPV infection at baseline if they reported more lifetime sexual partners, more new sexual partners within the last 6 months, were chlamydia trachomatis positive, or had an older age at first intercourse.
The data clearly shows an elevated risk of high-grade cervical neoplasia or adenocarcinoma in situ among young women reporting first intercourse closer to age of menarche. These data are consistent with an international study showing a higher risk of ICC among women reporting age of first intercourse earlier, at ≤14 compared with later at ≥25 years.2 Given the high-transmission probability of HPV, age at first intercourse can be considered as a relative proxy for a woman's first exposure to HPV infection.
Data from the present study also highlight the need to increase HPV vaccination rates among sexually naïve young women closer to their age of menarche, rather than suggesting parents wait to vaccinate their daughters closer to their first sexual intercourse. HPV vaccination initiation rates in 2011 were estimated at 52% among 13-year-old to 17-year-old adolescents in the USA,3 notably lower than those observed (around 80%) in similarly aged girls in Canada and Australia.
Counselling messages should focus on this window of susceptibility, given that female adolescents are at higher risk of future high-grade cervical disease if they start sexual activity earlier. Messages should include additional benefits to provide HPV vaccination at earlier ages in light of these data, and of data generated from HPV vaccine studies4 showing higher levels of neutralising antibodies generated in younger adolescents aged 10–14 years postvaccination compared with older female adolescents aged 16–26 years.
Competing interests JSS has received unrestricted grants and consultancies from GSK or Merck Corporation over the past 5 years.