To Örebro University

BACKGROUND: The aim of this study was to examine the natural course of HPV infection in women of 60 years and older who were HPV positive at inclusion, and any association between HPV positivity in historical samples and dysplasia outcome. METHODS: Eighty-nine women aged 60-82 years, who tested positive for HPV between 2012 and 2016 were included. Sampling for cytology and/or histology was also performed. HPV genotyping was carried out on archived material back to 1999.

RESULTS: Of the 89 HPV-positive women 16 had HSIL, 34 had LSIL and 39 were benign at inclusion. Of the women with HSIL, 50.0% had the same HPV type in the archive samples, 12.5% had another type, and 37.5% were HPV negative. Among the 34 women with LSIL, 47.1% had the same HPV type in archive samples, 5.8% had another type, and 47.1% were HPV negative. Of the 39 women without dysplasia at inclusion, 25.6% had the same HPV type in archive samples, 5.1% had another HPV type and 69.2% were HPV negative.

CONCLUSION: Surprisingly few of the elderly women thus seem to have a history with the same or any HPV infection the years before being diagnosed with an HPV infection and dysplasia. The significance of an HPV infection for dysplasia development in elderly women is still not fully understood.

PURPOSE: Cervical cancer prevention for older women can be challenging since there are no specific guidelines for this group. This study aimed to determine the incidence of oncogenic HPV and HPV-related dysplasia in elderly women 5 years after being HPV negative.

METHODS: Invited women participated five years earlier in a study where self-sampling for HPV testing was applied, at this time, they were all HPV negative. The women were now, five years later invited to perform self-sampling for HPV testing. Women with a positive result performed a repeat HPV test. Those with a positive repeat HPV test were examined by colposcopy, biopsy and cytology.

RESULTS: Of the 804 invited women, 634 (76.9%) agreed to participate in the study and a self-sampling kit was sent to them. Of these, 99.6% (632/634) sent a sample to the HPV laboratory. The participation rate in each age group was 93.3% at age 65, 74.0% at age 70, 80.7% at age 75 and 64.6% at age 80. Overall 18 women (2.8%, 95% CI 3.2 to 6.0) were HPV positive in the first test and 8 (1.3%, 95% CI 0.6 to 2.6) in the second test. Sampling for the second test was done on average 5.4 months after the first test. Fifty per cent (4/8) of the women with a positive repeat test had dysplasia in histology.

CONCLUSION: The incidence of HPV in previously HPV-negative elderly women was low. Among women who were HPV positive in a repeat test, there was a high prevalence of low grade dysplasia.

BACKGROUND: There are various society-specific guidelines addressing adjuvant brachytherapy (BT) after surgery for endometrial cancer (EC). However, these recommendations are not uniform. Against this background, clinicians need to make decisions despite gaps between best scientific evidence and clinical practice. We explored factors influencing decision-making for adjuvant BT in clinical routine among experienced European radiation oncologists in the field of gynaecological radiotherapy (RT). We also investigated the dose and technique of BT.

METHODS: Nineteen European experts for gynaecological BT selected by the Groupe Européen de Curiethérapie and the European Society for Radiotherapy & Oncology provided their decision criteria and technique for postoperative RT in EC. The decision criteria were captured and converted into decision trees, and consensus and dissent were evaluated based on the objective consensus methodology.

RESULTS: The decision criteria used by the experts were tumour extension, grading, nodal status, lymphovascular invasion, and cervical stroma/vaginal invasion (yes/no). No expert recommended adjuvant BT for pT1a G1-2 EC without substantial LVSI. Eighty-four percent of experts recommended BT for pT1a G3 EC without substantial LVSI. Up to 74% of experts used adjuvant BT for pT1b LVSI-negative and pT2 G1-2 LVSI-negative disease. For 74-84% of experts, EBRT + BT was the treatment of choice for nodal-positive pT2 disease and for pT3 EC with cervical/vaginal invasion. For all other tumour stages, there was no clear consensus for adjuvant treatment. Four experts already used molecular markers for decision-making. Sixty-five percent of experts recommended fractionation regimens of 3 × 7 Gy or 4 × 5 Gy for BT as monotherapy and 2 × 5 Gy for combination with EBRT. The most commonly used applicator for BT was a vaginal cylinder; 82% recommended image-guided BT.

CONCLUSIONS: There was a clear trend towards adjuvant BT for stage IA G3, stage IB, and stage II G1-2 LVSI-negative EC. Likewise, there was a non-uniform pattern for BT dose prescription but a clear trend towards 3D image-based BT. Finally, molecular characteristics were already used in daily decision-making by some experts under the pretext that upcoming trials will bring more clarity to this topic.

In Sweden, about 30% of the cervical cancer cases occur in women older than 60 and the mortality rate is as high as about 70% in this age group. There is a lack of knowledge concerning the prevalence of infection with oncogenic types of HPV, and cervical dysplasia in women of 60 years and older. Screening for oncogenic types of HPV is more effective than cytology in reducing the incidence of cervical cancer. It is established that self-collected samples are equally accurate as clinician-taken cervical samples when a validated PCR-based test is used for analysis. 

Objectives: The overall aim was to gain knowledge about HPV infection and cervical dysplasia prevalence in elderly women and to evaluate the acceptability of repeated self-sampling at home for HPV testing.

Material and Methods: In Paper I, we investigated the prevalence of HPV and HPV-related cervical dysplasia in 1051 elderly women aged 60 to 89 attending an outpatient gynecology clinic. A gynecologist collected these samples. In Paper II, repeated self-sampling at home for HPV testing was offered to 375 women in each of the four age groups 60, 65, 70, and 75. In Paper III, we carried out a descriptive study with quantitative and qualitative methods to describe older women’s experiences of self-sampling. In Paper IV, we investigated the incidence of oncogenic HPV and HPV-related dysplasia among 632 women aged 65 to 80 years who five years earlier had a negative HPV test.

Results: The prevalence of HPV was just over 4% both when the samples were collected by a clinician (Paper I) and by self-sampling (Paper II). The majority of women positive in both the first and second HPV tests had dysplasia in histology. Of the women with dysplasia in histology, more than 80% had normal cytology. In Paper II, a self-collected sample was provided by 59.5% of the invited women. In Paper III, 97.2% of eligible women answered the survey, and 13 of 16 invited women participated in the interviews. Most of them reported that they prefer self-sampling because it was easy to perform, less embarrassing, and less time-consuming than a clinic visit. In Paper IV, the incidence of oncogenic HPV was 2.8% in the first test and 1.3% in the second test, and mild cervical dysplasia was found in 50% of women with persistent HPV infection.

Conclusions: A significant proportion of elderly women were found to have a persistent HPV infection. Among them, there was a high prevalence of dysplasia as diagnosed by histology. Cytology showed extremely low sensitivity. Self-sampling at home combined with repeat HPV testing was well accepted among older women.