Stefanie J Klug

Worldwide burden of cervical human papillomavirus (HPV) in women over 50 years with abnormal cytology: a systematic review and meta-analysis

Introduction More than half of global cervical cancer cases occur among women older than 50. However, global estimates regarding the human papillomavirus (HPV) prevalence among this population are lacking, especially for women with abnormal cytology. Therefore, we conducted a systematic review and meta-analysis to estimate the worldwide HPV prevalence in women aged 50 and older with abnormal cytology. Methods We searched PubMed, Scopus and Web of Science for quantitative studies reporting any or high-risk (HR)-HPV prevalence for women 50 years and older with abnormal cytology (atypical squamous cells of undetermined significance and higher). We extracted data on world region, subregion, cervical lesion type, recruitment setting, HPV test, year of study conduct and HPV prevalence from the included studies. We assessed the risk of bias of the included studies using a modified Newcastle-Ottawa scale. We estimated the pooled prevalence and 95% CIs of any-HPV and HR-HPV using random-effects models, considering the world regions. Additionally, we estimated the prevalence by HPV type, lesion type and age groups. Results Overall, 113 studies met the inclusion criteria, of which 104 were included in the meta-analysis. Among women aged 50 and older with abnormal cytology, the estimated global pooled prevalence of any-HPV from 53 studies, including 14 585 women, was 54.5% (95%CI, 46.0 to 62.8%), and the HR-HPV prevalence from 85 studies, covering 33 672 women, was 43.0% (95%CI, 36.6 to 49.5%). There was a higher HR-HPV prevalence among women with high-grade lesions and women living in the African continent. No major differences in HR-HPV prevalence between the age groups of women over 50 years were found. The most common single HPV types worldwide were 16 and 52, with pooled prevalence estimates of 12.0% (95%CI, 8.0% to 17.7%) and 8.4% (95%CI, 4.4% to 15.4%), respectively. Conclusion Our findings highlight the relevance of targeted screening interventions among women 50 years and older. To achieve the elimination of cervical cancer, age-inclusive screening strategies should be considered. PROSPERO registration number CRD42021241365.

Impact of opportunistic screening on squamous cell and adenocarcinoma of the cervix in Germany: A population-based case-control study

Background We investigated the uptake of opportunistic cervical cancer screening (CCS) and other risk factors and their association with cervical cancer in Germany in a case-control study. Methods and findings We recruited incident cases of cervical cancer (ICD-10 C53) diagnosed between 2012 and 2016 and matched with three population-based controls, based on age and region of residence. Cases and controls reported their CCS participation during the past ten years (frequent: every three years; no or infrequent: less than every three years) and other relevant variables. We fitted conditional logistic regression models, reporting odds ratios (OR) and 95% confidence intervals (95% CI). We report overall and stratified analyses by histologic group (squamous cell–SCC, and adenocarcinoma–AC), T category (T1 and T2+), and age (<50 and ≥50 years). We analysed 217 cases and 652 matched controls. 53.0% of cases and 85.7% of controls attended CCS frequently. In the overall adjusted model, no or infrequent participation in CCS (OR 5.63; 95% CI 3.51 to 9.04), having had more than one sexual partner (OR 2.86; 95%CI 1.50 to 5.45) and obesity (OR 1.69; 95% CI 1.01 to 2.83) were associated with cervical cancer. Twelve years of schooling (OR 0.37; 95% CI 0.23 to 0.60) and a net monthly income of €3000 or more (OR 0.50; 95% CI 0.30 to 0.82) were protective factors. In the stratified analyses, no or infrequent participation was associated with T1 (OR 4.37; 95% CI 2.48 to 7.71), T2+ (OR 10.67; 95% CI 3.83 to 29.74), SCC (OR 6.88; 95% CI 4.08 to 11.59) and AC (OR 3.95; 95% CI 1.47 to 10.63). Conclusion Although women who frequently attended CCS were less likely to develop cervical cancer, especially larger tumours, the high proportion of cases who had been frequently screened prior to diagnosis underscores the need to investigate the quality of cytology and treatment of precancerous lesions in Germany.

HPV vaccination leads to decrease of anogenital warts and precancerous lesions of the cervix uteri in young women with low vaccination rates: a retrospective cohort analysis

Abstract Background Although the human papillomavirus (HPV) vaccine has been recommended in Germany for girls since 2007, no organised vaccination programme was introduced and HPV vaccine coverage remains low. We investigated the HPV vaccination rates from 2008 to 2018 and the effects of HPV vaccination on anogenital warts and precancerous lesions in young women in Bavaria, Germany, a state with low vaccination rates. Methods Retrospective analyses of claims data from the Bavarian Association of Statutory Health Insurance Physicians (KVB) on females born between 1990 and 2009 (9 to 28 years old in 2018) were conducted to calculate vaccination rates by birth cohort, proportion of vaccine types administered and incidence of anogenital warts and precancerous lesions of the cervix uteri. 942 841 Bavarian females 9 to 28 years old with available information on HPV vaccination were included to calculate vaccination rates. For the outcome analyses, data from 433 346 females 19 to 28 years old were analysed. Hazard ratios (HR) were computed from univariable and multivariable Cox regression models comparing vaccinated and unvaccinated women, considering type of vaccine used and contraceptive prescription. Results 40·9% of 18-year-olds and only 13·3% of 12-year-olds were fully vaccinated in 2018 in Bavaria. Gardasil® and Gardasil9® were most commonly administered. Vaccinated compared to unvaccinated women had a lower incidence of anogenital warts and cervical lesions, however only small differences were detected between fully and partially vaccinated women. Fully vaccinated women had a 63% (HR 0·37 (95% confidence interval (CI) 0·34 to 0·40) and 23% (HR 0·77, 95%CI 0·71 to 0·84) lower risk of anogenital warts and cervical lesions, respectively. Women who were prescribed contraceptives prior to vaccination had a 49% higher risk of developing anogenital warts (HR 1·49, 95%CI 1·25 to 1·79) or cervical lesions (HR 1·49, 95%CI 1·27 to 1·75) compared to vaccinated women without contraceptive prescription. Conclusions The evaluation of the effects of HPV vaccination in Bavaria showed a promising decline of anogenital warts and precancerous lesions in vaccinated young women. However, an increase in vaccination rates is necessary to achieve a greater population impact in preventing HPV-related diseases.

Epidemiology of cervical cancer in elderly women: Analysis of incidence, treatment, and survival using German registry data

AbstractBackgroundCervical cancer (CC) screening is generally recommended until age 65. The incidence of CC could be underestimated, particularly in older women, due to a lack of hysterectomy correction. Furthermore, elderly women (≥65 years) are more often diagnosed with late‐stage disease and have worse outcomes than younger patients. This study aims to provide an in‐depth overview of CC in Germany.MethodsIncidence rates of CC (ICD‐10 C53) were determined using data from the German Centre of Cancer Registry data (ZfKD) of six federal state registries. Incidence was corrected by using hysterectomy prevalence values from a real‐world study. The distribution of treatment modalities (surgery, chemotherapy, radiation therapy) was assessed. Relative survival was calculated using the period approach (2011–2015). Survival was stratified by tumor (T) stage and histological type.ResultsIn total, 14,528 CC cases were included, 27.6% of which occurred in elderly women. Cumulative (2001–2015) age‐standardized incidence rates were 12.5 per 100,000 women without hysterectomy correction and 15.5 per 100,000 women after hysterectomy correction (+24% relative change). A lower proportion of elderly women were treated, especially in advanced tumor stages. Younger women (20–64 years) had a higher 5‐year relative survival compared to elderly women: 76.7% versus 46.9%, respectively. Survival was worse with increasing stage and for glandular histological subgroups, particularly among elderly women.ConclusionsCC incidence in elderly women is underestimated and survival is lower compared to younger women in Germany. Due to the high disease burden in elderly women, screening and treatment strategies need to be improved.