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Post-Op HPV Vaccine Cuts Cervical Precancer Recurrences

<ѻý class="mpt-content-deck">— Plus osteoporosis in gynecologic cancer survivors, and a novel approach to CIN2/3
MedpageToday

Though the 2020 in-person was put on hold due to the ongoing COVID-19 pandemic, the meeting's scientific abstracts have now been released, and a selected few are summarized below.

Adjuvant HPV Vaccine Reduces Repeat Cervical Precancers

Women undergoing surgery for high-grade cervical intraepithelial neoplasia (CIN)2/3 had significantly lower risk for recurrence if they subsequently received a human papillomavirus (HPV) vaccination, a meta-analysis and systematic review found.

Among nearly 3,000 women undergoing surgical excision, recurrence of high-grade dysplasia (CIN2/3) occurred in 1.7% of women who received vaccination, as compared with 4.7% of those that received placebo or surgery alone (relative risk 0.34, 95% CI 0.22-0.55), reported Kim Levinson, MD, of Johns Hopkins University School of Medicine in Baltimore.

Risk of any-grade CIN was also significantly lower with vaccination than without (6.3% vs 9.7%, respectively, RR 0.67, 95% CI 0.52-0.85).

Moreover, when examining studies that looked at incidence of high-grade lesions carrying the HPV16/18 subtypes, fewer women in the vaccination group later developed these subtypes than the placebo or surgery-only group (0.9% vs 2.0%, RR 0.41, 95% CI 0.20-0.85).

"Not only can this vaccine prevent HPV-related cancer ... but it also appears to help reduce the risk of recurrent dysplasia in women that already have HPV-related abnormalities," Levinson said in a statement.

Among 2,984 women included in the six trials examined, 45.6% received an adjuvant HPV vaccination following surgery and 54.5% received placebo or surgery alone. Overall, 3.3% had a recurrence of CIN2/3.

In four studies that looked at the HPV16/18 subtypes, 49 women developed a recurrent HPV16/18-associated lesion, 35 of which were high-grade. Risk of any HPV16/18-associated dysplasia recurrence was also reduced with vaccination (1.1% vs 3.1%, RR 0.35, 95% CI 0.18-0.67), the study found.

Risk of Osteoporosis in Gynecologic Cancer Survivors

In a retrospective analysis, younger survivors of ovarian or uterine cancers were found to be at significantly increased risk of osteoporosis starting in the first year post-treatment.

In the sample of nearly 200 women, receipt of chemotherapy at 1 year (β=10.9, P=0.03) and smoking status at 5 years (β=52.4, P<0.01) were the only post-treatment factors that appeared to predict this elevated risk, according to Janelle Sobecki, MD, MA, of University of Wisconsin-Madison.

While pretreatment bone mineral density (BMD) was a predictor at multiple time points:

  • 1 year: β=0.7 (P<0.01)
  • 3 years: β=0.7 (P=0.02)
  • 5 years: β=0.8 (P<0.01)

For their study, Sobecki's group looked at 185 women age 65 and under (median 55 years) with either ovarian (78.1%) or uterine (21.9%) cancers with at least one baseline and follow-up CT scan. Mean BMI among the cohort was 32. Most were treated with chemotherapy (78.1%), while 17.1% received radiation therapy.

"Adequate treatment of osteoporosis relies on timely and appropriate bone mineral density screening in order to identify those at risk," Sobecki said in a statement. "It is especially important for younger gynecologic cancer survivors who have a longer life expectancy and may experience premature bone loss from oophorectomy (removal of the ovaries) and chemotherapy."

BMD as measured by Hounsfield units (HU) were significantly reduced from baseline at all time points measured (P<0.001 for all):

  • 1 year: 146.5 HU vs 179.4 HU at baseline
  • 3 years: 141.9 HU vs 176.0 HU at baseline
  • 5 years: 140.3 HU vs 179.1 HU at baseline
  • >5 years: 123.63 HU vs 175.78 HU at baseline

Women in the study had an estimated osteoporosis risk of 4.3% at baseline, and their risk subsequently increased to 7.4% by year 1, 15.7% by year 3, 18.0% by year 5, and 23.3% beyond 5 years.

Pilot Study Sees Potential for Novel Precancer Tx

In a phase I study, a self-administered vaginal insert with the anti-malarial drug artesunate showed promise as a less invasive treatment for high-grade cervical precancers.

Among 28 patients with CIN2/3 who underwent the treatment, 67.9% had histologic regression (to CIN1 or less), reported Cornelia Trimble, MD, also of Johns Hopkins University School of Medicine.

And among the 19 patients that experienced histologic regression, nine (47.4%) also had clearance of their baseline HPV genotypes.

"To have a self-administered, inexpensive, non-surgical treatment option that has minimal cold-chain requirements, for preinvasive HPV disease would change the landscape of care for patients, not only here in the U.S., but also in low-resource settings," Trimble told ѻý. "We reported an overall 68% rate of histologic regression in CIN2/3, the immediate precursor lesion of all cervical squamous cancers, and are testing topical artesunate to treat pre-invasive HPV disease in other tissue sites, including anal and vulvar disease."

Patients in the study underwent either one (50 mg or 200 mg), two (200 mg), or three (200 mg) 5-day treatment cycles before receiving an interval colposcopy in weeks 6 to 9 and standard-of-care surgical resection at week 15. Adverse events were said to be "mild and self-limited" and a randomized phase II study is being planned.

Disclosures

Trimble disclosed relevant relationships with Inovio Pharmaceuticals and Frantz Viral Therapeutics.

Levinson and Sobecki-Rausch disclosed no relevant relationships with industry.

Primary Source

Society of Gynecologic Oncology

Lichter K, et al "Adjuvant HPV vaccination with surgical excision to prevent recurrent CIN2+: A systematic review and meta-analysis" SGO 2020; Abstract 120.

Secondary Source

Society of Gynecologic Oncology

Trimble CL, et al "A first-in-human proof-of-concept trial of intravaginal artesunate to treat cervical intraepithelial neoplasia (CIN2/3)" SGO 2020; Abstract LBA1.

Additional Source

Society of Gynecologic Oncology

Sobecki-Rausch J, et al "Bone loss and osteoporosis risk in younger gynecologic cancer survivors" SGO 2020; Abstract 130.