Ola Forslund

High‐risk human papillomavirus genotypes in previously unscreened reproductive‐age women in Ethiopia: A community‐based cohort study

AbstractHigh‐risk human papillomavirus (hrHPV) genotype is needed for adequate cervical cancer screening and HPV vaccination program evaluation as recommended by different guidelines. We aimed to assess the rate of HPV infection and HPV genotype distribution using vaginal self‐sampling in a cohort of unscreened reproductive‐age women in Ethiopia. A community‐based cohort study was conducted with women aged 23–46 living in Adama, Ethiopia. A total of 885 self‐collected vaginal swabs were obtained and tested for hrHPV genotypes with the real‐time polymerase chain reaction technique. The overall hrHPV prevalence was 21.1% (187/885, 95% confidence interval [CI]: 18.5–24.0). Among women living with human immunodeficiency virus, 46% (30/56) (95% CI: 33.7–59) were hrHPV positive compared with 19% (157/820) (95% CI: 16.2–22) of human immunodeficiency virus‐negative women. The most frequent genotypes were HPV16 (3.1%), HPV51 (3.1%), HPV35 (2.6%), HPV56 (2.6%), HPV52 (2.4%), HPV31 (2.5%), and HPV39 (2.5%). Among the 187 HPV‐positive women in self‐samples, HPV 16/18 was found in 21% (39), HPV 16/18/45 was found in 24% (44), and HPV 16/18/31/33/45/52/58 was prevalent in 56% (104). Out of 116 biopsies, 7% (8) had cervical intraepithelial lesions and worse identified. Of these eight cervical intraepithelial lesions and worse patients, only 25% tested positive for HPV‐16; none tested positive for HPV‐18 or 45. One out of five women tested positive for hrHPV genotypes. Other HPV genotypes not covered by the quadrivalent HPV vaccine but associated with clinically significant cervical high‐grade lesions or cancer were detected in 75%. It is more effective to prevent cervical cancer by switching to the nine‐valent HPV vaccine.

Co‐testing in cervical screening among 40‐ to 42‐year‐old women is unreasonable

AbstractIntroductionThe screening program for cervical cancer in Sweden recommends the use of primary human papillomavirus (HPV) screening for women aged ≥30 to 65 years. Co‐testing with both HPV analysis and cytology is recommended at the first screening after the age of 40 years. To fulfil co‐testing, all screened women aged 40–42 years within the region of Skåne were co‐tested. The aim of the audit was to investigate the proportion of severe dysplasia as diagnosed by cytology and histological follow‐up among women with Aptima HPV‐negative tests. We also calculated the cost of adding the cytology to the HPV primary screening program.Material and MethodsThe local cytology registry was used to identify women aged 40–42 years who attended screening and were co‐tested during the 4 years from January 2017 to December 2020. The Aptima HPV messenger RNA assay detects 14 HPV types. For Aptima HPV‐negative women with high‐grade cytology or histological high‐grade squamous intraepithelial lesions (HSILs), we performed extended HPV typing for 40 HPV types with polymerase chain reaction using modified GP5+/6+ primers followed by a Luminex assay. To estimate the added cost of using cytology to identify each histologically confirmed cervical HSIL case among Aptima HPV‐negative women, we used the current cost of €21.2 per cytology evaluation at our laboratory.ResultsOf 19 599 women, 5.8% (1137/19 599) had abnormal cytology. Among Aptima HPV‐negative women, 0.11‰ (2/18 132) had histologically confirmed HSIL. One of the women was infected with HPV18 and the other with HPV73 at the diagnosis of HSIL. The calculated cost to find one HSIL, by adding cytology to HPV‐negative cases, was approximately €200 000.ConclusionsThe clinical benefit of a single cytology co‐test added to an HPV‐based screening program in women aged 40–42 years appears doubtful and economically unreasonable.

Cervix cytology samples revealed increased methylation of the human markers FAM19A4/miR124‐2 up to 8 years before adenocarcinoma

AbstractIntroductionMethylation analysis of the promoter region of tumor‐suppressor genes has previously shown high sensitivity for detection of high‐grade cervical intraepithelial neoplasia (CIN) and cancer. HPV‐testing has a high sensitivity to identify women at risk to develop cancer, and has been implemented in cervical screening programs in several countries. But in most HPV‐positive women the infection will clear and they will not develop cancer. Testing for methylation could help to identify women who have potentially progressive cervical disease and need closer follow‐up. The goal of the present study was to investigate the potential use of methylation as a triage test of HPV‐positive women in the screening program.Material and methodsA collection of liquid‐based cytology (LBC) samples from 106 women, collected between 4 months and 8 years before histologically confirmed cervical cancer or CIN3, was analyzed for hypermethylation of the human genes FAM19A4 and miR124‐2.ResultsMethylation was detected in 45% (33/73) of normal LBC samples from women who later developed CIN3+, compared with 10% (3/31) of normal LBC samples from women without subsequent dysplasia (P = 0.0006). Overall, methylation was detected in 39% (14/36), 51% (19/37), 61% (14/23) and 70% (7/10) of LBC samples from women who later developed CIN3, adenocarcinoma in situ (AIS), squamous cell carcinoma (SCC) and adenocarcinoma (ADC), respectively. Positive methylation analysis was not significantly more frequent than abnormal cytology of atypical squamous cells of unclear significance or worse (ASCUS+) in LBC samples collected 4 months to 8 years before SCC or AIS; however, prior to the development of ADC, methylation was observed in 7/10 LBC samples, despite normal cytology. Overall, LBC samples collected before invasive cancer (ADC and SCC) were more frequently positive in the methylation analysis than in cytological analysis of ASCUS+ (P = 0.048). For LBC samples collected more than 2 years before the development of AIS, SCC or ADC, methylation analysis showed a higher positivity rate than cytology did.ConclusionsTesting for methylation of FAM19A4/miR124‐2 as a triage for HPV‐positive women would be useful to identify women at risk of cancer development, especially adenocarcinoma. Further studies are needed to estimate the cost‐effectiveness before introducing methylation testing in the screening program.

Cervical cancer in Region Skåne, Sweden 2017–2020 after the implementation of primary HPV screening: A quality assurance audit

AbstractIntroductionPrimary human papilloma virus (HPV) screening to detect cervical cancer and dysplastic lesions was implemented in Region Skåne 2017 for women aged 30–70. The aim of this study was to characterize the screening history of women diagnosed with cervical cancer to evaluate the performance of the screening program, as well as to assess the cancer treatments given and shortcomings in the follow‐up of women with cervical dysplasia.Material and methodsWe performed a quality assurance audit. The data was collected from the National Cervical Cancer Prevention Registry, Region Skåne Labmedicin database and the Melior Journal system in 2017–2020.ResultsWe identified 247 women diagnosed with invasive cervical cancer in Region Skåne in 2017–2020. Of these, 35 (14.2%) had a screening history over at least two screening rounds before diagnosis. There were 25 (10.1%) women diagnosed with cervical cancer in between screening intervals, i.e., interval cancer. The most common screening history in women with cervical cancer was irregular screening (143, 57.9%), followed by women being above screening age (44, 17.8%). HPV was detected in 96% of the cases, either in cervical cytology or in the tumor tissue. The screening program detected the disease in 96 (38.9%) of the patients, 149 (60.3%) were diagnosed through symptoms and two (0.80%) as a result of incidental findings.ConclusionsThe most powerful tool in the prevention of cervical cancer is screening program attendance. Prolongation with HPV screening among elderly women will also reduce the incidence of cervical cancer. Today, such cancers are usually discovered when symptoms appear.