Five-Year Cervical (Pre)Cancer Risk of Women Screened by HPV and Cytology Testing

Uijterwaal, Margot H.; Polman, Nicole J.; Kemenade, Folkert J. van; Haselkamp, Sander Van Den; Witte, Birgit I.; Rijkaart, Dorien; Berkhof, Johannes; Snijders, Peter J.F.; Meijer, Chris J.L.M.

doi:10.1158/1940-6207.capr-14-0409

Cited by 28 publications

(28 citation statements)

References 33 publications

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“…Another Dutch screening study, in which women were followed for five years, reached a similar conclusion. 29 In a US study evaluating the value of co-testing done every three years to identify women at high risk of CIN3+, researchers also concluded that HPV positive women with negative cytology accrued a substantial risk of CIN3+ over five years, and thus needed follow-up. 17 …”

Section: Comparison With Other Studiesmentioning

confidence: 99%

Safety of extending screening intervals beyond five years in cervical screening programmes with testing for high risk human papillomavirus: 14 year follow-up of population based randomised cohort in the Netherlands

Dijkstra

Zummeren

Rozendaal

et al. 2016

BMJ

Self Cite

105

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ObjeCtivesTo provide an early risk assessment of extending screening intervals beyond five years for a human papillomavirus (HPV) based cervical screening programme in the Netherlands. Design 14 year follow-up of a population based randomised cohort from the POBASCAM randomised trial.setting Organised cervical screening in the Netherlands, based on a programme of three screening rounds (each round done every five years).PartiCiPants 43 339 women aged 29-61 years with a negative HPV and/or negative cytology test participating in the POBASCAM trial.interventiOns Women randomly assigned to HPV and cytology co-testing (intervention) or cytology testing only (control), and managed accordingly. Main OutCOMe MeasuresCumulative incidence of cervical cancer and cervical intraepithelial neoplasia (CIN) grade 3 or worse (CIN3+). Associations with age were expressed as incidence rate ratios. In HPV positive women, reductions in CIN3+ incidence after negative cytology, HPV type 16/18 genotyping, and/or repeat cytology were estimated. resultsThe cumulative incidence of cervical cancer (0.09%) and CIN3+ (0.56%) among HPV negative women in the intervention group after three rounds of screening were similar to the cumulative among women with negative cytology in the control group after two rounds (0.09% and 0.69%, respectively). Cervical cancer and CIN3+ risk ratios were 0.97 (95% confidence interval 0.41 to 2.31, P=0.95) and 0.82 (0.62 to 1.09, P=0.17), respectively. CIN3+ incidence was 72.2% (95% confidence interval 61.6% to 79.9%, P<0.001) lower among HPV negative women aged at least 40 years than among younger women. No significant association between cervical cancer incidence and age could be demonstrated. CIN3+ incidence among HPV positive women with negative cytology, HPV 16/18 genotyping, and/or repeat cytology was 10.4 (95% confidence interval 5.9 to 18.4) times higher than among HPV negative women. COnClusiOnsLong term incidences of cervical cancer and CIN3+ were low among HPV negative women in this study cohort, and supports an extension of the cervical screening interval beyond five years for women aged 40 years and older. HPV positive women with subsequent negative cytology, HPV16/18 genotyping, and/or repeat cytology have at least a fivefold higher risk of CIN3+ than HPV negative women, indicating that HPV based programmes with long intervals (>five years) should be implemented with risk stratification.trial registratiOn POBASCAM trial number ISRCTN20781131. IntroductionRandomised controlled clinical trials have shown that screening for high risk human papillomavirus (HPV) leads to earlier detection of cervical intraepithelial neoplasia (CIN) grade 3 or worse (CIN3+) than cytology, [1][2][3][4] and provides better protection against cervical cancer. 5-10 Primary HPV testing shows positive results more often than primary cytology testing in the general screening population, and subsequent triage testing of HPV positive women (by use of cytology and of genotyping of HPV subtypes 16 and 18) has been recommend...

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Section: Comparison With Other Studiesmentioning

confidence: 99%

Safety of extending screening intervals beyond five years in cervical screening programmes with testing for high risk human papillomavirus: 14 year follow-up of population based randomised cohort in the Netherlands

Dijkstra

Zummeren

Rozendaal

et al. 2016

BMJ

Self Cite

105

View full text Add to dashboard Cite

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“…This may result in anxiety amongst women, even if their CIN3+ risk is statistically low enough for them to return to the next screening round. It is therefore important for the last triage test to be negative; a repeat visit for cytologic testing at 6 to 12 months could be used to accomplish this . A disadvantage of repeat testing is loss to follow‐up, while existing CIN3+ lesions may be missed …”

Section: Discussionmentioning

confidence: 99%

“…A limitation of this study is the lack of histology in the group of women who had a NILM cytologic triage result and, after 6 months of follow‐up, a hrHPV‐negative result and a NILM cytologic result. However, the Ministry of Health did not approve colposcopy with random biopsies in these women, because the risk of CIN2+ in his group of women is low . Furthermore, women with inadequate follow‐up were excluded from this study, which might over represent women with NILM cytology at baseline, and the current study also has a relative short duration of follow‐up.…”

Section: Discussionmentioning

confidence: 99%

“…It is therefore important for the last triage test to be negative; a repeat visit for cytologic testing at 6 to 12 months could be used to accomplish this. 7,25 A disadvantage of repeat testing is loss to follow-up, while existing CIN31 lesions may be missed. 26 An important strength of this study is the study design, comparable to the future Dutch cervical cancer screening programme with hrHPV testing and cytology triage.…”

Section: Cancer Therapy and Preventionmentioning

confidence: 99%

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The clinical value of HPV genotyping in triage of women with high-risk-HPV-positive self-samples

et al. 2016

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Cytology alone, or combined with HPV16/18 genotyping, might be an acceptable method for triage in hrHPV-cervical cancer screening. Previously studied HPV-genotype based triage algorithms are based on cytology performed without knowledge of hrHPV status. The aim of this study was to explore the value of hrHPV genotyping combined with cytology as triage tool for hrHPV-positive women. 520 hrHPV-positive women were included from a randomised controlled self-sampling trial on screening non-attendees (PROHTECT-3B). Eighteen baseline triage strategies were evaluated for cytology and hrHPV genotyping (Roche Cobas 4800) on physician-sampled triage material. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), referral rate, and number of referrals needed to diagnose (NRND) were calculated for CIN21 and CIN31. A triage strategy was considered acceptable if the NPV for CIN31 was 98%, combined with maintenance or improvement of sensitivity and an increase in specificity in reference to the comparator, being cytology with a threshold of atypical cells of undetermined significance (ASC-US). Three triage strategies met the criteria: HPV161 and/or LSIL; HPV161 and/or HSIL; (HPV161 and/or HPV181) and/or HSIL. Combining HPV161 and/or HSIL yielded the highest specificity (74.9%, 95% CI 70.5-78.9), with a sensitivity (94.4%, 95% CI 89.0-97.7) similar to the comparator (93.5%, 95% CI 87.7-97.1), and a decrease in referral rate from 52.2% to 39.5%. In case of prior knowledge of hrHPV presence, triage by cytology testing can be improved by adjusting its threshold, and combining it with HPV16/18 genotyping. These strategies improve the referral rate and specificity for detecting CIN31 lesions, while maintaining adequate sensitivity.A persistent cervical infection with high-risk human papillomavirus (hrHPV) is a necessary cause for the development of cervical neoplasia. 1 Western countries therefore increasingly consider implementation of primary hrHPV testing for cervical cancer screening, and replace primary cytology screening. The main concern surrounding the use of hrHPV testing for primary screening is its relatively low specificity, the direct result of the assay's inability to distinguish transient from persistent HPV infection. Therefore, additional triage is required to identify women with the highest risk of cervical precancer or cancer, in need of treatment. 2 In the Netherlands, primary hrHPV testing will soon be implemented in the organised screening programme. The proposed strategy for hrHPV-positive women is cytology

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“…HPVs are double‐stranded DNA viruses that are classified into 5 genera (α, β, γ, μ, and ν) 8, 9. αHPVs (eg, mucosal HPV types 16 and 18) are responsible for the development of cervical carcinoma and other mucosal SCCs, including anogenital and oropharyngeal carcinomas 10. The role of skin βPVs in cSCC carcinogenesis is controversial,9, 11, 12 but evidence for etiologic involvement is accumulating 13, 14, 15, 16, 17.…”

Section: Introductionmentioning

confidence: 99%

Human papillomavirus and posttransplantation cutaneous squamous cell carcinoma: A multicenter, prospective cohort study

Bavinck

Feltkamp

Green

et al. 2018

American Journal of Transplantation

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Organ transplant recipients (OTRs) have a 100‐fold increased risk of cutaneous squamous cell carcinoma (cSCC). We prospectively evaluated the association between β genus human papillomaviruses (βPV) and keratinocyte carcinoma in OTRs. Two OTR cohorts without cSCC were assembled: cohort 1 was transplanted in 2003‐2006 (n = 274) and cohort 2 was transplanted in 1986‐2002 (n = 352). Participants were followed until death or cessation of follow‐up in 2016. βPV infection was assessed in eyebrow hair by using polymerase chain reaction–based methods. βPV IgG seroresponses were determined with multiplex serology. A competing risk model with delayed entry was used to estimate cumulative incidence of histologically proven cSCC and the effect of βPV by using a multivariable Cox regression model. Results are reported as adjusted hazard ratios (HRs). OTRs with 5 or more different βPV types in eyebrow hair had 1.7 times the risk of cSCC vs OTRs with 0 to 4 different types (HR 1.7, 95% confidence interval 1.1‐2.6). A similar risk was seen with high βPV loads (HR 1.8, 95% confidence interval 1.2‐2.8). No significant associations were seen between serum antibodies and cSCC or between βPV and basal cell carcinoma. The diversity and load of βPV types in eyebrow hair are associated with cSCC risk in OTRs, providing evidence that βPV is associated with cSCC carcinogenesis and may present a target for future preventive strategies.

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Five-Year Cervical (Pre)Cancer Risk of Women Screened by HPV and Cytology Testing

Cited by 28 publications

References 33 publications

Safety of extending screening intervals beyond five years in cervical screening programmes with testing for high risk human papillomavirus: 14 year follow-up of population based randomised cohort in the Netherlands

Safety of extending screening intervals beyond five years in cervical screening programmes with testing for high risk human papillomavirus: 14 year follow-up of population based randomised cohort in the Netherlands

The clinical value of HPV genotyping in triage of women with high-risk-HPV-positive self-samples

Human papillomavirus and posttransplantation cutaneous squamous cell carcinoma: A multicenter, prospective cohort study

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