Genital Human Papillomavirus Infection: Incidence and Risk Factors in a Cohort of Female University Students R.L. Winer, Shu-Kuang Lee, J.P. Hughes, D. E. Adam, N.B. Kiviat, L.A. Koutsky American Journal of Epidemiology, 2003:157(3) Presented by Patrick Heyman Palm Beach Atlantic University

Background ● Human Papillomavirus (HPV)  Most prevalent STI ~50% of women  Some strains cause genital/anal warts  Some strains cause cervical cancer  Good incidence data is not available  Risk factors are largely unknown

Research Objectives ● Determine the cumulative incidence of HPV infection in a group of female university students ● Study the relationship of various characteristics on HPV infection in women

Methods ● Recruitment  1990 to 1997  Letters sent to a “Random sample” of students  Eligible women (Washington residents, planned to stay for three years)  603 women recruited out of ~3000 eligible women

Methods ● Initial visit  Medical and sexual history, social history ● Subjects saw nurse practitioner every 4 months  Face-to-face interview  Standardized pelvic examination ● Updated behavioral and medical information ● New sex partners ● Separate cervical and vulvovaginal swabs sent for HPV DNA tests ● Saliva tests sent for HPV DNA tests

Methods ● Response variable  HPV DNA: yes/no ● Generic probe ● HPV Types (Strain)  Time until infection ● Previously sexually active: from enrollment date ● Virgins: from first sexual encounter

Results ● 553 enrolled women with adequate samples ● 109 (19.7 percent) had HPV DNA at first visit ● 444 HPV-DNA negative at enrollment  4,307 total visits  41.2 (st dev 16.3) months follow-up  9.7 (st dev 3.4) visits per person  4.3 months median time between visits  19.2 (st dev 0.5) years, mean age at enrollment  148 virgins, 94 became sexually active  1.8 (st dev 1.7) mean lifetime number of partners

Cumulative 24 month Incidence ● Sexually active at enrollment  38.8% (95% CI, 33.3% %) ● Virgins who initiated sexual activity  38.9% (95% CI, 29.4 – 50.3) ● Vulvovaginal swabs + before cervical swabs ● No difference  Between years (p = 0.53)  Virgins vs already sexually active (p = 0.35)  0, 1-2, 3 partners at enrollment (p = 0.28) ● Oral: 5/2500 samples

Cumulative Incidence of HPV Among Sexually Active Women Cumulative incidence of human papillomavirus (HPV) infection among women sexually active and HPV negative at enrollment (n = 296) in Washington State, 1990?2000. Vertical bars, 95% confidence intervals at 12, 24, 36, 48, and 60 months.

Cumulative Incidence of HPV Among Virgins at Enrollment

HR after Acquisition of a New Partner

Potential Risk Factors

Other Risk Factors ● Non-pentrative sex for virgins  9.7% vs. 1.3% ● Non risk factors  Partner's (age, race, educational level, circumcision status, sexually transmitted disease history)  Partnership (condom use and alcohol consumption)  Tampon use  Cesarean delivery  Nongenital warts

HPV Types

Discussion ● End prevalence was similar to three other studies done in young women ● Risk after new partner similar to risk for virgins who became sexually active ● Risk is greatest 5 – 8 months after acquiring a new partner ● Risk decreases after 13 months ● Vulvovaginal swabs may be more sensitive

Discussion ● Smoking was associated with increased risk even after adjusting for other risk factors  Most other studies do not show a link between smoking and risk for HPV  Perhaps some confounding sexual behavior  Perhaps current smoking is the key, and the visits every four months were more accurate in recording smoking ● Oral contraceptives were associated with increased risk, unlike other studies

Discussion ● Condoms showed no reduction in risk consistent with six other studies ● HPV is transmissible by non-penetrative sex ● A very small percentage of non-sexually active have HPV (<2%) in accordance with other studies ● Oral-penile sex was frequent, but oral HPV low  Oral HPV infection is low  Or Test to detect it is not sensitive enough

Limitations ● Only 20% of recruited women participated ● Comparative studies are often clinic based, which show higher infection rates ● Unable to “capture all forms of non-penetrative sex” ● Reporting bias ● Recall bias (four month intervals) ● Unable to capture frequency of sexual exposures or concurrent partners

Limitations ● HPV DNA testing methods are much better now ● Cohort may not generalize to other populations  Regional bias  Healthy, young, university females ● Older ● Immunocompromised ● Higher partner change

Conclusion/Implications for Practice ● New partners increase risk of HPV infection ● Not knowing your partner's sexual history increases risk ● 0 – 12 months after new partner acquisition is the key screening period ● Virgins can have HPV ● Non-penetrative sex can lead to infection