Sexual behavior and factors associated with young age at first intercourse and HPV vaccine uptake among young women in Germany: implications for HPV vaccination policies

Background In Germany, immunization against human papillomaviruses (HPV) is free of charge for all females aged 12 to 17 years. Since HPV infection rates rise soon after first intercourse, immunization against HPV should be completed before sexual debut. Knowledge of country-specific data on age at first intercourse and related risk factors is important to optimize prevention of HPV and other sexually transmitted infections. Therefore, the primary aim of this study was to describe sexual behavior in young women in Germany. Secondary aims were to identify factors that are (i) associated with younger age at first intercourse and (ii) with HPV vaccine uptake. Methods Between 2010 and 2012, we conducted a cross-sectional study among randomly selected women aged 20 to 25 years in Germany. We used a structured, self-administered questionnaire to collect sociodemographic data, information on sexual habits such as age at first intercourse, and information on HPV vaccine uptake. We used univariate and multivariate logistic regression analyses to identify factors associated with younger age at first intercourse and with HPV vaccine uptake. Results A total of 823 women (response rate: 14.2%) participated, 785 (95.4%) of which reported having had intercourse already. 70% of these women experienced first intercourse before the age of 18 years. However, less than 5% were younger than 14 years at sexual debut. Younger age at first intercourse was independently associated with a higher number of sexual partners, smoking, and past pregnancies. HPV vaccine uptake was associated with higher education, whereas smoking and a migrant background reduced the chance of being vaccinated. Conclusion In Germany, only a small proportion of women experienced first intercourse before the age of 14 years. Younger age at first intercourse was associated with behavior that might increase the risk of HPV infections or other sexually transmitted infections. Therefore, to optimize the HPV vaccination strategy, HPV vaccination series should be completed before the age of 14 years in Germany.


Background
Human papillomaviruses (HPV) are the most common sexually transmitted viruses [1], with a life-time risk of cervical infection of up to 80% in the female population [2]. Two safe and effective vaccines covering high-risk HPV types 16 and 18 are licensed. Since HPV infection rates rise soon after first intercourse [3,4] and since HPV vaccines effectiveness is reduced in infected individuals [5], vaccination series should be completed before sexual debut. In Germany, the Standing Committee on Vaccination (STIKO) recommends HPV vaccination free of charge for all females aged 12 to 17 years since 2007 [6]. Both, the quadrivalent and the bivalent vaccine are available in Germany.
Several risk factors for HPV transmission have been identified so far, with high-risk sexual behavior, such as younger age at first sexual intercourse [1,7] and higher numbers of present or recent sexual partners [8][9][10] being the most important ones. However, few studies have analyzed sexual behavior in Germany and -to the best of our knowledge -no study has assessed factors associated with younger age at first intercourse in Germany so far.
Since national data on sexual behavior are important to optimize prevention strategies against sexually transmitted infections, the primary aim of this study was to describe sexual behavior in young women in Germany. Secondary aims were to identify factors that are associated (i) with younger age at first intercourse and (ii) with HPV vaccine uptake.

Study design and study population
This study was nested in a study designed to determine HPV prevalence in Germany via home-based self-sampling [11]. Briefly, we conducted a cross-sectional study among 20 to 25 year old women in Germany between 2010 and 2012. We used a two-step cluster sampling approach based on the protocol of the German Health Interview and Examination Survey for Adults [12]: Within selected sampling points women were randomly selected from local registration offices. An invitation letter, a self-sampling kit, and a questionnaire were mailed to each woman who gave written informed consent. Self-sampling was performed by cervicovaginal lavage (5 ml volume) with the first generation Delphi-Screener (Delphi-Bioscience, Scherpenzeel, The Netherlands) as described previously [13]. The study was approved by the local ethics committee (Charité, EA2/028/10) and registered at Deutsches Register Klinischer Studien (DRKS 00000599).

Questionnaire
With a structured, self-administered questionnaire in the German language we obtained information on sociodemographic factors, data on sexual behavior (such as age at first intercourse and number of lifetime and recent (i.e. in the previous 12 months) sexual partners), medical and smoking history, contraceptive use, past pregnancies, past delivery of a child, as well as HPV-vaccine uptake (time of vaccination and number of doses). The questionnaire has been developed by the Robert Koch Institute and was previously used in another study [14]. Details about the questionnaire and definitions are described elsewhere [11]. Data from the questionnaires were selfreported and not validated.

Statistical analysis
We calculated proportions on young age at first intercourse, contraceptive use and past pregnancies with corresponding 95% confidence intervals (95% CI). We evaluated the lifetime number of sexual partners by estimating the median, range and interquartile bounds (IQB). For comparison of proportions of categorical variables, we used chi-squared test and Fisher's exact test, and Student's t-test for numerical variables. Differences between three age groups (20-21, 22-23 and 24-25 years) were assessed by the Kruskal-Wallis-test for categorical variables and by analysis of variance (ANOVA) for continuous variables.
The age cut-off for 'young' age at first intercourse was defined as the lower quartile (age ≤ 14) and a 'high' number of lifetime sexual partners was defined as the upper quartile (≥ 7 partners) in the respective variable distribution. For assessing factors associated with HPV vaccine uptake, women with at least one HPV vaccine dose were defined as "vaccinated".
In order to identify factors associated with (i) young age at first intercourse and (ii) HPV vaccine uptake, we conducted univariate analyses for all binary or categorical exposure variables and calculated odds ratios (OR) and 95% confidence intervals (95% CI). We then used multivariate logistic regression analysis and included variables with a p-value <0.1 in univariate analysis. In addition, we included important potential confounding factors on the basis of the current literature. Two-sided hypothesis tests were performed and a p-value of less than 0.05 was considered as statistically significant. Missing data were treated as such and not imputed. We used the statistical software package STATA, version 11 (STATA Corp., College Station, TX, USA).

Representativeness of study population
We used data of the German Federal Statistical Office (as of 31 December 2011 [15]) to compare characteristics of our study population with the general German female population of the same age.

Overall study population
Overall, 823 out of 5805 women with a valid postal address (14.2%) completed the questionnaire and were included in the analysis ( Figure 1). Mean age of participants was 22.6 years (standard deviation (SD) = 1.6). Key characteristics of the study population compared to the general female population in Germany of the same age group are presented in Table 1.

Sexual behavior
Overall, 95.4% (95% CI, 93.7-96.7%) had experienced sexual debut at the time of the study. More than half of the women were 16 years or older at sexual debut, whereas only 4.6% (95% CI, 3.3-6.3%) were younger than 14 years (Table 2). 73.5% (95% CI, 70.3-76.5%) were living in a relationship and 69.6% (95% CI, 66.5-72.8%) reported having had just one sexual partner in the previous 12 months. The proportion of women with more than one sexual partner in the last 12 months was significantly higher among women not living in a relationship as compared to those living in a relationship (35.6% vs. 16.3%, p-value < 0.01).
Factors associated with young age at first intercourse 17.2% (95% CI, 14.7-20.0%) of sexually active women reported that they experienced first intercourse before or at age of 14 years (Table 2). More than half of the women were older than 15 years at sexual debut and one fourth was older than 17 years. In univariate analysis younger age at first intercourse (defined as ≤ 14 years) was independently associated with lower educational status, current smoking, a higher number of recent and lifetime sexual partners, bisexual experience, usage of contraceptive pill, past pregnancy, and genital warts (data not shown).
The final multivariate model indicated that current smoking, a higher number of sexual partners, and past pregnancy were independently associated with young age at first intercourse (Table 3). In addition, women with younger age at sexual debut were more likely to have bisexual experience and to have used the contraceptive pill. Adjusting for age did not substantially affect the model.

Contraception and pregnancy
A total of 92.7% (95% CI, 90.1-94.5%) women reported usage of any type of contraception, with the contraceptive pill and condoms being the most common ones ( Table 2). 10.8% (95% CI, 8.7-12.9%) of the participants had ever used a vaginal ring and 1.5% (95% CI, 0.6-2.3%) an implant. Overall, 80.8% (95% CI, 77.9-83.4%) of women stated that they would always use condoms during a one-night stand. However, the probability of consistent condom use decreased with an increasing number of a woman's lifetime sexual partners (p-value <0.01). The proportion of women with a previous pregnancy and who delivered a child was 8.6% (95% CI, 6.6-10.4%) and 5.6% (95% CI, 4.0-7.2%), respectively.
In multivariate analysis HPV vaccine uptake was independently associated with younger age and a higher educational status. Vice versa, active smoking and migrant background were associated with a lower chance of being vaccinated (Table 4).

Discussion
In this study, more than 70% of women experienced their first intercourse before age of 17, but less than 5% before age of 14. Factors strongly associated with younger age at first intercourse were a high number (≥ 7) of sexual partners during lifetime, current smoking and a past pregnancy. HPV vaccine uptake was higher in women with higher educational status, whereas uptake was lower in smokers and in women with a migrant background.
National data about sexual behavior in young adults is scarce in Germany. To optimize prevention strategies against sexually transmitted infections, these data is urgently needed. Our results on age at first intercourse are comparable with data obtained in other studies: Crochard et al. reported results from seven European countries where the majority of young women experienced sexual debut between 15 and 18 years (1st to 3rd quartile); less than 5% of girls in this study (4.6% in our study) were younger than 14 years [16]. In a large population-based study in four Nordic countries conducted 2004-2005, Jensen and colleagues found that 2.7% ─ 4.7% of women aged 18 to 25 years had experienced sexual debut at, or before age of 13 years, and 10.6% ─ 16% before the age of 15, respectively [17]. Finally, a representative survey on  youth sexuality among 14 to 17-year-olds in Germany in 2009 revealed that 66% of girls have had first sexual intercourse before the age of 18 (74% in our study) and 7% before the age of 15 (17% in our study) [18]. The use of contraceptives was very common in our study population, with the contraceptive pill and condoms being the most popular ones. 80% of participants reported that they would use condoms regularly during one-night stands. These findings might be a positive effect of an ongoing public campaign about condom use and prevention of sexually transmitted infections in Germany [19]. However, the probability of consistent condom use decreased with an increasing number of a woman's lifetime sexual partners. Regarding prevention strategies against sexually transmitted infections, benefits of consistent condom use needs to be addressed continuously towards young adults. Since condom use may imply a lesser protection against HPV infection than against several other sexually transmitted infections, [20,21] HPV vaccination needs to be promoted as well.
The fact that younger age at first intercourse is associated with risky (sexual) behavior is corroborated by other studies that have shown that early intercourse is associated with higher numbers of sexual partners, bisexual experience, smoking and early pregnancy later in life [22][23][24][25]. In addition, women with a higher number of sexual partners [17] also had less consistent condom use, which in turn increased the risk of acquiring sexual transmitted infections [23,24], including HPV. Several large population-based studies [8,9,11,26] found that a higher number of sexual partners independently increased the risk for HPV infection and, in consequence, increased the risk of pre-cancer and cancer lesions [27]. To this end, women with younger age at first intercourse are at particularly high risk for HPV infection and have the greatest need of getting vaccinated at younger age.
In line with current literature, HPV vaccine uptake was associated with higher education [28][29][30][31]. Interestingly, women with a migrant background had a lower chance of being vaccinated. A Canadian study assessing awareness, knowledge and attitudes towards the HPV vaccines found that awareness was higher in Caucasian compared to non-Caucasian women [32]. If the effect in our study is real and not affected by participation bias, efforts are needed to understand possible barriers against HPV vaccination in women with migrant background and to increase vaccine-uptake in this population. However, when factors associated with HPV vaccination are interpreted, the age of study participants (with regard to sexual debut) and endorsement date of the recommendation for HPV vaccination have to be taken into account. Women aged 25 years at the time of our study were 20-22 years old when HPV vaccination was adopted into the national immunization schedule in Germany. Therefore, it is not  surprising that a large proportion of the women received the vaccine after sexual debut. The findings of our survey have important implications for the target population for HPV vaccination in Germany: since rates of HPV rise soon after first intercourse and since HPV vaccination is less effective in infected individuals [3,4], HPV vaccination is recommended to be administered before sexual intercourse [33]. According to our data, HPV vaccination series in Germany should be completed before the age of 14 years, when the majority of girls had not experienced sexual debut. Physicians should be aware of these data when discussing the optimal time point of the HPV vaccination with their young patients and their parents. Finally, it should be considered, whether the HPV vaccination strategy could be optimized by preponing the recommended age at which HPV vaccination should be initiated.

Limitations
Some limitations of our study need to be taken into account. First, the response rate was low (14%) with the potential of introducing participation bias. Since this study was implemented in a population based survey to evaluate HPV prevalence using a self-sampling method, the response rate was comparable to a similar study [34]. However, women with a migrant background were underrepresented and those with a higher education were overrepresented. As educational status was independently associated with young age at first intercourse, it is possible that the true proportion of these women is higher than estimated by our study. However, other characteristics of our study sample, such as place of residency, living in a city, and smoking behavior were comparable to the German female population of similar age groups. Second, information on sexual behavior and vaccination status were self-reported and could be subject to misclassification. Third, due to the sensitive nature of the topic on sexual behavior, social desirability bias cannot be excluded. Although anonymity and confidentiality was ensured, women might have had the tendency to give more "desirable" answers with for example a lower number of sexual lifetime partners or an older age at first intercourse. Forth, a long time interval since relevant exposures (e.g., time at first intercourse) may have led to miscalculation by participants and may have influenced the magnitude of relative risk estimates.

Conclusion
Although hampered by its low response rate, our study indicate that in Germany the majority of young women experienced first sexual intercourse before the age of 18 years, but only a small proportion before the age of 14 years. Usage of the contraceptive pill and condoms was common in our study population. However, condom use may imply lesser protection against HPV than against other sexually transmitted infections, therefore HPV vaccination needs to be promoted as well. Since younger age at first intercourse was associated with behavior that might increase the risk of HPV infections, HPV vaccination series should be completed before the age of 14 years in Germany.