Optimal Cervical Cancer Screening in Women Vaccinated Against Human Papillomavirus

Kim, Jane J.; Burger, Emily A.; Sy, Stephen; Campos, Nicole G.

doi:10.1093/jnci/djw216

Cited by 77 publications

(80 citation statements)

References 34 publications

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“…Evidence of deterioration in the predictive value of cytology as a primary screen in immunized women has been documented, although this does not translate into poor performance as a triage of HR‐HPV‐positive samples . It is also worth noting that the extent of triage in immunized populations will reduce given evidence from modeling studies that indicate 10‐year screening starting aged 30 is optimal . Conclusions from modeling endeavors, while extremely helpful, clearly incorporate various assumptions and differing levels of vaccine‐uptake, type of vaccine and dimensions of program (including the detail of catch‐up immunization) will exert influence.…”

Section: ±P16 ± Ki67mentioning

confidence: 99%

Eurogin roadmap 2017: Triage strategies for the management of HPV‐positive women in cervical screening programs

Cuschieri

Ronco²,

Lörincz

et al. 2018

Intl Journal of Cancer

132

142

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Cervical cancer screening will rely, increasingly, on HPV testing as a primary screen. The requirement for triage tests which can delineate clinically significant infection is thus prescient. In this EUROGIN 2017 roadmap, justification behind the most evidenced triages is outlined, as are challenges for implementation. Cytology is the triage with the most follow-up data; the existence of an HR-HPV-positive, cytology-negative group presents a challenge and retesting intervals for this group (and choice of retest) require careful consideration. Furthermore, cytology relies on subjective skills and while adjunctive dual-staining with p16/Ki67 can mitigate inter-operator/-site disparities, clinician-taken samples are required. Comparatively, genotyping and methylation markers are objective and are applicable to self-taken samples, offering logistical advantages including in low and middle income settings. However, genotyping may have diminishing returns in immunised populations and type(s) included must balance absolute risk for disease to avoid low specificity. While viral and cellular methylation markers show promise, more prospective data are needed in addition to refinements in automation. Looking forward, systems that detect multiple targets concurrently such as next generation sequencing platforms will inform the development of triage tools. Additionally, multistep triage strategies may be beneficial provided they do not create complex, unmanageable pathways. Inevitably, the balance of risk to cost(s) will be key in decision making, although defining an acceptable risk will likely differ between settings. Finally, given the significant changes to cervical screening and the variety of triage strategies, appropriate education of both health care providers and the public is essential.

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Section: ±P16 ± Ki67mentioning

confidence: 99%

Eurogin roadmap 2017: Triage strategies for the management of HPV‐positive women in cervical screening programs

Cuschieri

Ronco²,

Lörincz

et al. 2018

Intl Journal of Cancer

132

142

View full text Add to dashboard Cite

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“…The decision to discontinue cervical screening and at what age and risk is a societal one; Swedish guidelines require a single negative HPV test at age 64 years or older, and Australian guidelines require a single negative HPV test at age 70–74 years . Still, it must be recognized that it is impractical and very cost ineffective to achieve zero lifetime risk of cervical cancer, even if women have been previously vaccinated against HPV . However, these results suggest that, at a minimum, a longer screening interval may be appropriate for these low‐risk, older women.…”

Section: Discussionmentioning

confidence: 99%

Absolute risks of cervical precancer among women who fulfill exiting guidelines based on HPV and cytology cotesting

Landy

Schiffman

Sasieni

et al. 2019

Intl Journal of Cancer

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US guidelines recommend that most women older than 65 years cease cervical screening following two consecutive negative cotests (concurrent HPV and cytology tests) in the previous 10 years, with one in the last 5 years. However, this recommendation was based on expert opinion and modelling rather than empirical data on cancer risk. We therefore estimated the 5-year risks of cervical precancer (cervical intraepithelial neoplasia grade 3 or adenocarcinoma in situ [“CIN3”]) following one, two, and three negative cotests among 346,760 women aged 55–64 years undergoing routine cotesting at Kaiser Permanente Northern California (2003–2015). Women with a history of excisional treatment or CIN2+ were excluded. No woman with one or more negative cotests was diagnosed with cancer during follow-up. Five-year risks of CIN3 following one, two, and three consecutive negative cotests were 0.034% (95% CI: 0.023%−0.046%), 0.041% (95% CI: 0.007%−0.076%), and 0.016% (95% CI: 0.000%−0.052%), respectively (ptrend<0.001). These risks did not appreciably differ by a positive cotest result prior to the one, two or three negative cotest(s). Since CIN3 risks following one or more negative cotests were significantly below a proposed 0.12% CIN3+ risk threshold for a 5-year screening interval, a longer screening interval in these women is justified. However, the choice of how many negative cotests provide sufficient safety against invasive cancer over a woman’s remaining life represents a value judgment based on the harms versus benefits of continued screening. Ideally, this guideline should be informed by longer-term follow-up given that exiting is a long-term decision.

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“…Cost-effectiveness models will help determine the optimal combination of HPV vaccination and screening in public health programs, and balance the effects of such approaches in different populations [19]. With the increasing demand under pressing health logistics for less screening in well-HPV-vaccinated cohorts (ie, those vaccinated primarily before becoming sexually active), strategies that combine HPV vaccination with simplified protocols of HPV screening and cytology triage, at least for women aged >30, will be of interest in many settings in the foreseeable future [19,23,24]. Besides, as herd immunity levels increase, the core design of screening schedules (e.g., screening intervals or screening start age) evolves, highlighting the importance of jointly optimizing both primary and secondary prevention strategies [25,26].…”

Section: Editorialmentioning

confidence: 99%

Crossroads of Primary and Secondary Cervical Cancer Prevention Strategies in Resource-Constrained Settings

Georgios¹

2017

JCPCR

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EditorialJ Cancer Prev Curr Res 2017, 7(4): 00246 cancer prevention. Besides, overtreatment of patients when clinicians fear future noncompliance leads to heightened patient anxiety and community mistrust of the health care system [1]. Nonetheless, lower socioeconomic status and inequalities represent fundamental problems which must be addressed in the new integrated strategies [3].More than 10 years have elapsed since the global launch of the first vaccine targeting an STI, namely the quadrivalent VLP HPV vaccine. Despite being highly successful, HPV vaccination programs have been particularly well executed in special settings where their implementation has been school-based [4]. The patchy coverage of vaccination target groups and the huge debate over HPV vaccination essentially stemmed from physicians and people's mixed attitudes towards vaccination, inaccurate information in the electronic and social media and the robust antivaccination movement among others. In hindsight, anecdotally some would argue that if the quadrivalent vaccine was globally marketed as an anti-wart vaccine without reference to cervical "precancer", it might have enjoyed more success.In the meanwhile, the inherent drawbacks of cytology (subjective nature, low sensitivity for detecting true cervical precancer requiring frequent re-screening) have been partially addressed with the wider implementation of HPV-related biomarkers which represent objective and more repetitive methods to screen for precancerous lesions [5]. Several DNA and mRNA HPV assays have gained FDA approval, other biomarkers (p16/Ki67 dual stain, viral genotyping, methylation markers) are being successfully used in daily clinical practice, and several others are still being validated in the assessment of HPV positive women [6]. This progress in HPV science has been the basis of calibrated cervical screening and triage options, and guidelines endorsed by the scientific committees. Therefore, the two approaches for controlling cervical cancer incidence have paved in parallel routes for a while; secondary prevention implementing cytology and HPV-related biomarkers for identifying precancer lesions, with subsequent resort to colposcopy; and HPV vaccination -virtually the incarnation of primary prevention. Even in the western world however, cervical screening is commonly opportunistic; or might be organized inconsistently across and within countries and regions. 7 In an excellent review addressing the flaws of secondary cervical prevention, the authors point at the differences between organized and opportunistic screening; in the former the basic principle is that the more women screened (as differentiated from the more tests done), the less morbidity and mortality from cervical cancer [7]. In contrast, opportunistic screening is often characterized by the over-screening of a minority of (some privileged) women, while those women most at risk tend to be screened rarely or not at all [7]. Thus, across all levels of screening coverage, increases in test sensitivity provide gre...

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Optimal Cervical Cancer Screening in Women Vaccinated Against Human Papillomavirus

Cited by 77 publications

References 34 publications

Eurogin roadmap 2017: Triage strategies for the management of HPV‐positive women in cervical screening programs

Eurogin roadmap 2017: Triage strategies for the management of HPV‐positive women in cervical screening programs

Absolute risks of cervical precancer among women who fulfill exiting guidelines based on HPV and cytology cotesting

Crossroads of Primary and Secondary Cervical Cancer Prevention Strategies in Resource-Constrained Settings

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