Evaluation of co-testing with cytology and human papillomavirus testing in cervical screening

Kleppe, Sara Nordqvist; Andersson, Helena; Elfström, K. Miriam; Dillner, Joakim

doi:10.1016/j.ypmed.2022.107364

Cited by 2 publications

(4 citation statements)

References 6 publications

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“…Continued evaluation of the screening program has shown that extremely few HPV-negative women have severe histology-confirmed dysplasia, even if the cytology is abnormal. [6][7][8] Cytology has a relatively low sensitivity and requires long training and continuous work to maintain high quality, which is a challenge for some laboratories. 9 Another problem with cytology triage is that cytotechnologists are hesitant to label the cytology as normal if they are aware that the woman is high-risk HPV-positive.…”

Section: Introductionmentioning

confidence: 99%

“…Continued evaluation of the screening program has shown that extremely few HPV‐negative women have severe histology‐confirmed dysplasia, even if the cytology is abnormal. 6 , 7 , 8 …”

Section: Introductionmentioning

confidence: 99%

“…According to Swedish guidelines, HPV‐positive women who have abnormal cytology of atypical squamous cells of undetermined significance or worse (ASCUS+) are referred for colposcopy, whereas HPV‐positive women with normal cytology are retested after 18 months when positive for HPV 16 or 18, and after 3 years when positive for other high‐risk HPV types. Continued evaluation of the screening program has shown that extremely few HPV‐negative women have severe histology‐confirmed dysplasia, even if the cytology is abnormal 6–8 …”

Section: Introductionmentioning

confidence: 99%

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

Lindroth,

Pedersen,

Alssamaray

et al. 2023

Acta Obstet Gynecol Scand

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IntroductionMethylation 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 analysed 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.

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Section: Introductionmentioning

confidence: 99%

“…Continued evaluation of the screening program has shown that extremely few HPV‐negative women have severe histology‐confirmed dysplasia, even if the cytology is abnormal. 6 , 7 , 8 …”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Lindroth,

Pedersen,

Alssamaray

et al. 2023

Acta Obstet Gynecol Scand

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“…Concurrent screening with HPV DNA testing, cytology and visual inspection (VIA or colposcopy) has been evaluated in various combinations in the context of research [8][9][10][11][12]. To the best of our knowledge, however, no prior study has evaluated the tritesting approach in routine clinical work, especially regarding its potential to reduce loss to follow-up in screening.…”

Section: Introductionmentioning

confidence: 99%

Tritesting in Battor, Ghana: an integrated cervical precancer screening strategy to mitigate the challenges of multiple screening visits and loss to follow-up

Effah,

Tekpor,

Mawusi Wormenor

et al. 2023

ecancer Journal

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Background Human papillomavirus (HPV) DNA testing is more sensitive than cytology for detecting cervical precancer; however, increasing reports of high-risk HPV (hr-HPV)-negative cases of cervical intraepithelial neoplasia (CIN) and even malignancy motivate the use of combined testing. We present our experience with ‘tritesting’, defined as the performance of HPV DNA testing, cytology and visual inspection in a single session at the Cervical Cancer Prevention and Training Centre, Ghana. We further determined the prevalence rates of hr-HPV infection, abnormal cytology and cervical lesions among women screened using tritesting. Methods This descriptive retrospective cross-sectional study assessed all women screened via tritesting between April 2019 to April 2023. HPV DNA testing was performed using the Sansure MA-6000, GeneXpert or AmpFire platforms. Visual inspection was performed using enhanced visual assessment mobile colposcopy or visual inspection with acetic acid. Liquid-based cytology was performed using cervical samples taken with a Cervex-Brush® and fixed in PreservCyt, while samples for conventional cytology were taken using an Ayre spatula and cytobrush. Results Among 236 women screened (mean age, 39.1 years (standard deviation, 10.9)), the overall prevalence rates of hr-HPV infection and cervical lesions were 17.8% (95% confidence interval (CI), 13.1–23.3) and 11.9% (95% CI, 8.0–16.7), respectively. Cytology yielded findings of atypical squamous cells of undetermined significance or worse in 2.5% (95% CI, 0.9–5.5) of women. Histopathology following loop electrosurgical excision procedure revealed CIN I (tritest positive) and CIN III (hr-HPV-positive, visual inspection ‘positive’, cytology-negative) in one woman each. Factors independently associated with hr-HPV infection among ‘tritested’ women were age ≥ 39 years, tertiary level of education and current contraceptive use. Twenty-seven out of 39 hr-HPV-positive women (69.2%; 95% CI, 52.4–83.0) showed a type 3 transformation zone and would have needed to be recalled for a cytologic sample to be taken in a ‘see and triage’ approach with HPV DNA testing and a visual inspection method. Conclusion This study brings tritesting into the spotlight, as an alternative to other methods, particularly for women who prefer this due to the advantage of a single visit to a health facility and being more cost-effective, if they have to travel long distances to access cervical screening services.

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Evaluation of co-testing with cytology and human papillomavirus testing in cervical screening

Cited by 2 publications

References 6 publications

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

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

Tritesting in Battor, Ghana: an integrated cervical precancer screening strategy to mitigate the challenges of multiple screening visits and loss to follow-up

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