In the JournalsPerspective

Mid-adult women remain at risk for incident, episodic HPV

Women aged 25 to 65 years reporting recent new male partners, multiple male partners or partners with concurrent relationships were nearly three times as likely to test positive for newly acquired high-risk HPV compared with those without recent sexual behavior, according to recent study data.

Despite this, approximately one-third of newly detected cases occurred among those who reported no recent partners or no risky sexual exposure, which researchers wrote suggests that a significant portion of HPV detections among mid-adult women are likely due to prior infection.

“Among women, the incidence of genital [HPV] infection peaks around 25 years of age and declines with increasing age,” they wrote. “With frequencies of divorce, dating and remarriage in mid-adulthood increasing, the risk of newly acquired [high-risk HPV (HR-HPV)] infection and subsequent cervical neoplasia might be greater now than among cohorts of mid-adult women in previous decades. In general, however, mid-adult women with recent new partners have been underrepresented in HPV studies.”

From 2007 to 2010, researchers recruited mid-adult women who were using online dating websites into a longitudinal study on genital HPV. Participants received mailed kits that contained questionnaires and self-administered vaginal sample collection materials. Women returned these to the researchers upon enrollment and continuously every 4 months up to four kits. Researchers tested the samples for HPV DNA using PCR and constructed separate analytical models for women based on sexual risk as determined by questionnaire responses.

Baseline samples from 420 women, and at least one usable follow-up, were included in the final analysis. Of these, the participants’ mean age was 35.7 years, and the median number of lifetime male sex partners was 11. Fifty-one percent reported at least one new male sex partner within 6 months of enrollment, and 71.2% returned the maximum number of samples.

The 12-month cumulative incidence of newly detected HR-HPV was 25.4% (95% CI, 21.3%-30.1%), translating to a 29.5 cases per 100 women-years incidence rate. Multivariable modeling found an association between HPV incidence and current hormonal contraceptive use (adjusted HR = 1.82; 95% CI, 1.17-2.83). Women with nine or more lifetime sexual partners were more likely than women with one to four lifetime partners to be diagnosed (aHR = 2.56; 95% CI, 1.15-5.69), and lifetime number of sex partners was directly associated with diagnosis risk when limiting the model to women with no male sex partners within the prior 6 months. When adjusting analysis for hormonal contraceptive use and marital status, women who reported multiple male partners, new male partners or casual male partners with one or more concurrent partnerships were 2.81 (95% CI, 1.38-5.69) times as likely to have incident HR-HPV than those who did not. This accounted for an estimated 64.4% of new detections. Results were unchanged when excluding women whose samples were collected more than 8 months apart.

This incidence among an aged cohort considered to be at higher risk for transmission is “considerably higher” than previous analyses which did not target women with new partners, the researchers wrote. In addition, the substantial portion of new detections among those who were not at risk suggested that many diagnoses could be the result of previous infections going undetected, a finding that “may be reassuring to women in monogamous sexual partnerships” who test positive.

“While prophylactic HPV vaccination in mid-adulthood is likely to provide some protection against new HR-HPV acquisition in high-risk women, the benefit may be limited,” the researchers wrote. “Future studies should seek to quantify the risks of cervical pre-cancer or cancer associated with HR-HPV infections that are newly acquired in mid-adulthood vs. those that represent reactivation or intermittent persistent detection.”

In a related editorial, Aaron C. Ermel, MD, and Kenneth H. Fife, MD, both of Indiana University School of Medicine, wrote that the incidence of episodic detection reported by the researchers raises new questions concerning cervical cancer screening and HPV vaccination for women in this age group. With additional evidence suggesting the possibility of waning natural immunity to HPV with age, future studies will need to address whether aged women at greater risk for acquisition should be included in regular vaccination.

“The implementation of cervical cytology screening, HPV DNA detection and vaccines targeting HR-HPV types represent major advances in public health. We now face the challenge of adapting these to all segments of the population at risk,” Ermel and Fife wrote. “Indeed, longitudinal cohort studies, in particular those that provide long-term follow-up from near the age of acquisition to mid-adulthood, are necessary to fully understand the impact of changing behaviors on screening and prevention.” – by Dave Muoio

Disclosure: The researchers report no relevant financial disclosures.

Women aged 25 to 65 years reporting recent new male partners, multiple male partners or partners with concurrent relationships were nearly three times as likely to test positive for newly acquired high-risk HPV compared with those without recent sexual behavior, according to recent study data.

Despite this, approximately one-third of newly detected cases occurred among those who reported no recent partners or no risky sexual exposure, which researchers wrote suggests that a significant portion of HPV detections among mid-adult women are likely due to prior infection.

“Among women, the incidence of genital [HPV] infection peaks around 25 years of age and declines with increasing age,” they wrote. “With frequencies of divorce, dating and remarriage in mid-adulthood increasing, the risk of newly acquired [high-risk HPV (HR-HPV)] infection and subsequent cervical neoplasia might be greater now than among cohorts of mid-adult women in previous decades. In general, however, mid-adult women with recent new partners have been underrepresented in HPV studies.”

From 2007 to 2010, researchers recruited mid-adult women who were using online dating websites into a longitudinal study on genital HPV. Participants received mailed kits that contained questionnaires and self-administered vaginal sample collection materials. Women returned these to the researchers upon enrollment and continuously every 4 months up to four kits. Researchers tested the samples for HPV DNA using PCR and constructed separate analytical models for women based on sexual risk as determined by questionnaire responses.

Baseline samples from 420 women, and at least one usable follow-up, were included in the final analysis. Of these, the participants’ mean age was 35.7 years, and the median number of lifetime male sex partners was 11. Fifty-one percent reported at least one new male sex partner within 6 months of enrollment, and 71.2% returned the maximum number of samples.

The 12-month cumulative incidence of newly detected HR-HPV was 25.4% (95% CI, 21.3%-30.1%), translating to a 29.5 cases per 100 women-years incidence rate. Multivariable modeling found an association between HPV incidence and current hormonal contraceptive use (adjusted HR = 1.82; 95% CI, 1.17-2.83). Women with nine or more lifetime sexual partners were more likely than women with one to four lifetime partners to be diagnosed (aHR = 2.56; 95% CI, 1.15-5.69), and lifetime number of sex partners was directly associated with diagnosis risk when limiting the model to women with no male sex partners within the prior 6 months. When adjusting analysis for hormonal contraceptive use and marital status, women who reported multiple male partners, new male partners or casual male partners with one or more concurrent partnerships were 2.81 (95% CI, 1.38-5.69) times as likely to have incident HR-HPV than those who did not. This accounted for an estimated 64.4% of new detections. Results were unchanged when excluding women whose samples were collected more than 8 months apart.

This incidence among an aged cohort considered to be at higher risk for transmission is “considerably higher” than previous analyses which did not target women with new partners, the researchers wrote. In addition, the substantial portion of new detections among those who were not at risk suggested that many diagnoses could be the result of previous infections going undetected, a finding that “may be reassuring to women in monogamous sexual partnerships” who test positive.

“While prophylactic HPV vaccination in mid-adulthood is likely to provide some protection against new HR-HPV acquisition in high-risk women, the benefit may be limited,” the researchers wrote. “Future studies should seek to quantify the risks of cervical pre-cancer or cancer associated with HR-HPV infections that are newly acquired in mid-adulthood vs. those that represent reactivation or intermittent persistent detection.”

In a related editorial, Aaron C. Ermel, MD, and Kenneth H. Fife, MD, both of Indiana University School of Medicine, wrote that the incidence of episodic detection reported by the researchers raises new questions concerning cervical cancer screening and HPV vaccination for women in this age group. With additional evidence suggesting the possibility of waning natural immunity to HPV with age, future studies will need to address whether aged women at greater risk for acquisition should be included in regular vaccination.

“The implementation of cervical cytology screening, HPV DNA detection and vaccines targeting HR-HPV types represent major advances in public health. We now face the challenge of adapting these to all segments of the population at risk,” Ermel and Fife wrote. “Indeed, longitudinal cohort studies, in particular those that provide long-term follow-up from near the age of acquisition to mid-adulthood, are necessary to fully understand the impact of changing behaviors on screening and prevention.” – by Dave Muoio

Disclosure: The researchers report no relevant financial disclosures.

    Perspective
    Katina Robison

    Katina Robison

    Winer and colleagues’ recently published prospective cohort study evaluating the incident detection of high-risk HPV among women aged 25 to 65 years raises the question, “Should we vaccinate women over the age of 26?”

    In this study, women with new recent sexual partners, multiple male partners or male partners who were casual were three times as likely to have a new high-risk HPV infection detected. Currently, HPV vaccination is not recommended for women older than 26 years, but this study suggests we should revisit this recommendation. While vaccinating all women older than 26 years may be overkill, there may be a select group of women who would benefit. This may be even more important in older women, as we know the chances of clearing a new HPV infection decrease significantly after the age of 30.

    While this study is thought-provoking, it is difficult to clearly differentiate those women who had a new high-risk–HPV infection from those who had rededication of an old infection. Further studies would be useful to better define those women over the age of 26 who may benefit from the HPV vaccination, but it is difficult to imagine the HPV vaccination recommendations will not eventually change to include a subset of women over the age of 26.

    • Katina Robison, MD
    • Assistant professor of obstetrics/gynecology and medicine at the Warren Alpert Medical School of Brown University

    Disclosures: Robison reports no relevant financial disclosures.