HPV vaccination does not mean lower risk for cervical intraepithelial neoplasia

A history of HPV vaccination may not reliably help physicians triage women for less intensive management after an abnormal cervical screening test result, according to researchers.

“Many prior studies have shown that HPV vaccination, especially during the childhood vaccination schedule, is beneficial to lower the incidence of cervical cancer in that population,” Neal M. Lonky, MD, MPH, of the Kaiser Permanente Southern California department of obstetrics and gynecology, told Healio. “In this study, we asked a different question related to management of women screened for cervical cancer: If a woman in adulthood receives an abnormal cervical screening test, is she less likely to harbor high-grade cervical cancer precursors that may require treatment to prevent cancer if she was vaccinated? Thus, can colposcopy — a test in which a doctor or nurse use a colposcope to closely examine a patient’s cervix, vagina and vulva for abnormal cells — or biopsy be safely delayed or triaged with repeated testing in HPV-vaccinated women if they have an abnormal screening test result?”

To address this question, Lonky and colleagues conducted a retrospective study of women aged 21 to 38 years who received a colposcopy between July 2017 and August 2018 at Kaiser Permanente Southern California’s Orange County facilities. Additional eligibility criteria included abnormal screening results leading to the colposcopy and at least one pathology diagnosis from the colposcopy visit. In all, 730 participants were included in the study.

The researchers collected data on demographics, clinical and sexual history, and HPV vaccination status. They additionally performed HPV genotyping for tissues from confirmed cervical intraepithelial neoplasm grade 2 or higher diagnoses (CIN2+). The analysis examining the association between HPV vaccination history and CIN2+ diagnosis — as well as for HPV16/18-positive CIN2+ as an alternative outcome — was completed using a multilevel generalized linear model with a logic function, adjusting for screening results and potential confounders.

According to the researchers, 170 patients — or 23.2% of the study population — had a histologic CIN2+ diagnosis. Among these individuals, 40% demonstrated histologic HPV 16 and/or 18 positivity.

In all, 43% of the total study population had received their HPV vaccination prior to colposcopy. However, among these patients, 69% were aged 18 to 26 years at the time of vaccination.

A history of HPV vaccination overall (OR = 1.07; 95% CI, 0.7-1.64), prior to sexual debut (OR = 1.11; 95% CI, 0.55-2.24), before age 18 years (OR = 0.96; 95% CI, 0.49-1.91) or with complete dosing (OR = 0.84; 95% CI, 0.53-1.35) were not associated with lower odds of CIN2+ diagnosis, compared with no vaccination.

Similarly, prior HPV vaccination was not significantly associated with the odds of a HPV16/18-positive CIN2+ diagnosis. In addition, Lonky and colleagues noted that eight patients — or 5% of all CIN2+ cases — demonstrated HPV 16 on CIN2+ histologic PCR analysis, despite reported or documented HPV vaccination prior to sexual debut. This included two patients who started vaccination prior to age 13 years.

“We found that a significant percentage of women undergoing colposcopy with abnormal screening had received HPV vaccination — mostly vaccinated after the age of 13,” Lonky said. “The chance of having evidence of high-grade cervical lesions was not significantly less in vaccinated women than the nonvaccinated women who had colposcopy. It’s important to note that the vast majority of the women in our cohort were over the age of 12 when they received their HPV vaccination, and it’s possible they were exposed to HPV through sexual activity before they received their vaccination.”

“HPV vaccination status, especially among those receiving the vaccine later in life — ie, after age 13 — is not a factor that should change our existing colposcopy referral guidelines, currently based on screening test results, prior disease history and patient age,” he added. “We also note, though, that more research is needed among the population of women who received their HPV vaccination at an earlier age to determine if receiving the HPV vaccination between the ages of 9 and 12 may change the need for colposcopy after an abnormal screening result.”