Chapter 7: Achievements and limitations of cervical cytology screening

doi:10.1016/j.vaccine.2006.05.113

Vaccine

Volume 24, Supplement 3, 21 August 2006, Pages S63-S70

https://doi.org/10.1016/j.vaccine.2006.05.113 Get rights and content

Abstract

This chapter reviews the contribution of cervical cytology, what makes it successful, the management of screen positives and how technological advances may affect its use in the future. Cervical screening has saved hundreds of thousands of lives but has not been available to women in the poorest countries. In countries where wide coverage has been achieved and quality assurance is in place, incidence and death rates have fallen by over 50% even though cervical cytology is logistically complex. The management of high-grade cervical intraepithelial neoplasia (CIN) is very effective, but low-grade cytological abnormalities require care to avoid over-treatment. The increasing rate of human papillomavirus (HPV) testing and the prospect of prophylactic vaccination will change the way cervical cytology is used, possibly giving way to HPV testing as the primary test in secondary prevention.

Introduction

This monograph sets out to explore the role of HPV as the principal cause of cervical cancer, as well as the means of screening for it and ultimately, through vaccination, the means of preventing it. It is appropriate, therefore, to devote a chapter to reflect on the achievements of cervical cytology as the standard for secondary prevention that has been variably deployed in developed healthcare systems for 40 years. It is currently estimated that systematic screening can reduce death rates from cervical cancer by 70% or more. In the United Kingdom, this translates into at least 1000 lives per year among a population of 50 million [1], [2]. It is also considered highly cost-effective. With an incidence beginning to rise in the late 20s and peaking in the mid 40s, loss of life years per cervical cancer case is often high, both as a mother and wife. When extended across North America, Europe, Australasia and the Pacific Rim, the number of lives saved will have run into hundreds of thousands. Unfortunately, the benefits of screening have not been available to countries in the developing world due to a lack of resources, and this has been disastrous for women, with 80% of cervical cancer incidence and mortality occurring in these countries [3].

Treatment of pre-invasive lesions identified in screening programmes, has also enabled preservation of fertility, which is a crucial issue for many women, and, as a consequence, women around the world have developed great confidence in the “Pap Test” or “cervical smear”. Thus, any strategies to replace it will need to outperform it in terms of effectiveness, cost-effectiveness, safety and acceptability.

This chapter will review the successes and failures of cervical cytology from an epidemiological and clinical viewpoint and will touch on the psychosocial costs which some women endure. New technology has impacted on cytological techniques and has the potential to do so further in the near future.

Section snippets

Pathogenesis of cervical cancer

Cervical cancer arises in the so-called transformation zone of the uterine cervix. This is the area which undergoes physiological metaplasia from glandular to squamous epithelium at the onset of adolescence. HPV infection is very common in young women after the onset of sexual activity, and when it persists, the viral oncoproteins produce perturbation of the cell-cycle controls, resulting in CIN. At their mildest (CIN-1), these lesions are generally no more than manifestations of HPV infection,

Public health considerations

Since the development of cytology-based cervical cancer screening using the Pap smear in the mid 20th century, Pap smears and new cytological technologies such as liquid-based cytology have been implemented for secondary prevention of cervical cancer. Although some have argued that there is no direct evidence of the impact of cytology screening on cervical cancer, such as evidence from a randomized clinical trial (RCT), there are overwhelming and convincing epidemiologic data to infer the

What makes a screening programme work?

When viewed from the perspective of a population as opposed to that of an individual woman, there are a number of key considerations which come into play when assessing why programmes work. Insight can be gained from the UK screening programme, which was launched in the late 1980s after 20 years of essentially opportunistic activity. Between 1988 and 1995, the incidence fell by 40% (Fig. 2) and by 2004 the death rate from cervical cancer had fallen by almost 50% [9]. The key to this success lay

Overview

The management of screen positives has been a crucial element in the success of cervical screening. The challenge has always been to ensure that the benefits of treating women who are found through colposcopic examination to have CIN outweigh the risks of treatment. There is, of course, a spectrum in this benefit/harm balance. While excision of CIN-3 is mandatory by most, destructive treatment is still used by some. Aggressive treatment in women with CIN-1 risks doing more harm than good, and

Technology in cervical cytology

The Pap test has survived virtually unchanged for 50 years, a testimony to its efficacy. During the last 10 years, however, two technological advances have come to the forefront. The first of these is liquid-based cytology (LBC) where, instead of spreading the exfoliate, obtained with a spatula, onto a glass slide and fixing, the exfoliate is stirred immediately into a pot containing a preservative and, on receipt at the laboratory, the cells are aspirated onto a filter and similarly stained on

Conclusions

Cervical screening works but there are some major challenges ahead. The most significant is that most women in the world have been denied any form of prevention, which, if continued, will result in a million deaths from this disease over the next 5 years. If this situation is to change there has to be a new approach, such as a strategy of primary prevention, a possibility offered by vaccination. Otherwise, affordable, cost-effective strategies of secondary prevention, which are feasible in

Disclosed potential conflicts of interest

HCK: Consultant (GlaxoSmithKline)

JTC: Consultant (Digene Corporation, GlaxoSmithKline, 3M Pharmaceuticals); Speakers Bureau (Digene Corporation, 3M Pharmaceuticals); Data and Safety Monitoring Board (Merck and Co., Inc.)

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In cytopathology education, Virtual Microscopy e-learning modules (VM-eLM) have achieved remarkable results in the improvement and personalization of learning. However, it remains to be determined whether these modules can significantly contribute to improving the accuracy of cytological diagnosis. The aim of this work was to create a VM-eLM for gynecologic cytopathology education designed to improve screening and interpretation skills in two groups of cytologists: experienced and nonexperienced.
The module was designed in Moodle with both Whole Slide Images and Static Images taken from Papanicolaou smears that were diagnosed as: negative for intraepithelial lesion, low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion, squamous cell carcinoma, or adenocarcinoma. We assessed the effectiveness of the module using 1) clinical quality indicators to measure skill development and 2) a user survey.
After training, participants significantly improved their cytological screening skills, decreasing their false negative diagnosis by 78% in the non-experienced group and eliminating them entirely in the experienced group. Nonexperienced participants also significantly increased their recognition of low-grade squamous intraepithelial lesion and high-grade squamous intraepithelial lesion by 31% and 50%, respectively. Participants positively evaluated the module, highlighting its novelty, the possibility to train remotely, the immediate feedback and the quality of the Whole Slide Images.
We designed, implemented and tested a VM-eLM for Gynecologic Cytopathology Education that improved cytological screening skills for both non-experienced and experienced cytologists, also increasing the diagnostic accuracy of preinvasive lesions by less experienced cytologists. The module was positively evaluated by participants, who perceived an improvement in their interpretive skills.
Exploring factors associated with preferences for human papillomavirus (HPV) self-sampling among racially- and ethnically-diverse women in Minnesota: A cross-sectional study
2023, Preventive Medicine Reports
Pap tests are still underutilized by minority women due to limited awareness of cervical cancer screening (CCS), inadequate health care access, and cultural or religious beliefs. Human papillomavirus (HPV) self-sampling, a new CCS tool, has demonstrated potential to overcome some of these barriers. In 2021, women aged 30–65 years old were recruited across Minnesota to complete an online survey. The survey assessed five outcome measures related to HPV self-sampling: (1) awareness of test; (2) self-efficacy to conduct test; (3) location preference of test (clinic vs. home); 4) collector preference (self vs. clinician); and (5) preference of CCS strategy (HPV self-sampling vs. Pap test). Modified Poisson regressions tested associations between sociodemographic variables and outcomes. A total of 420 women completed the survey, of which 32.4% identified as Non-Hispanic white, 22.2% as Hispanic, 12.6% as Black/African-American, 28.3% as Asian, 1.9% as American Indian/Alaskan Native, and 1.4% as more than two races. Few women had heard of HPV self-sampling (6.5%), but a majority reported high self-efficacy to perform self-sampling (75.3%). Women also reported higher preferences for completing an HPV test in the clinic (52.2%) and for performing a self-collected HPV test themselves (58.7%), yet would choose a traditional Pap test over HPV self-sampling (56.0%). The low level of HPV self-sampling awareness, across all racial/ethnic groups, suggests a strong opportunity to promote widespread educational efforts around this new tool. Future HPV self-sampling research efforts should examine educational interventions targeted at healthcare providers to educate and encourage women on the importance of self-collection options.
Deep learning for computational cytology: A survey
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Computational cytology is a critical, rapid-developing, yet challenging topic in medical image computing concerned with analyzing digitized cytology images by computer-aided technologies for cancer screening. Recently, an increasing number of deep learning (DL) approaches have made significant achievements in medical image analysis, leading to boosting publications of cytological studies. In this article, we survey more than 120 publications of DL-based cytology image analysis to investigate the advanced methods and comprehensive applications. We first introduce various deep learning schemes, including fully supervised, weakly supervised, unsupervised, and transfer learning. Then, we systematically summarize public datasets, evaluation metrics, versatile cytology image analysis applications including cell classification, slide-level cancer screening, nuclei or cell detection and segmentation. Finally, we discuss current challenges and potential research directions of computational cytology.
Recurrences of precancerous lesions after conservative treatment: Operational results after a decade in Abidjan
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Il demeure un risque important de récidive de néoplasies intraépithéliale quel que soit le type de traitement conservateur. Ce travail a pour but d’en apprécier le taux en opérationnel.
Étaient incluses dans cette étude multicentrique transversale, toutes les femmes consentantes ayant bénéficiées d’un traitement conservateur sur les sites identifiés depuis plus de 12 mois. Le critère de jugement était la récidive des lésions précancéreuses du col de l’utérus lors de l’inspection visuelle à l’acide acétique pratiqué par un seul praticien pour limiter une variabilité inter-observateur. La collecte et l’analyse des données a été fait sur le logiciel Stata 13. Nous avons réalisé une analyse univariée puis multivariée avec une régression logistique.
Deux cent soixante-dix-neuf ont participées à cette étude avec un âge moyen de 37,44 (σ = 7,31 ans). Au total, 52,33 % étaient VIH positif. De plus, 63,44 % étaient traitées par cryothérapie versus 36,66 % par électroconisation à l’anse diathermique. La prévalence globale des récidives était de 8,96 %. L’analyse multivariée avec une régression logistique a permis de conclure le risque de récidive était 5,72 fois (OR = 1,69–19,29 ; p = 0,005) plus élevé avec la cryothérapie et 2,85 fois plus important (OR = 1,04–7,82 ; p = 0,042) chez les femmes porteuses du VIH.
Le risque de récidive est proportionnellement élevé avec la cryothérapie et le statut VIH suggérant une adaptation des protocoles de suivi strict à notre contexte africain du fait du manque de moyen logistique cytocolposcopique.
There remains a significant risk of recurrence of intraepithelial neoplasia regardless of the type of conservative treatment. The aim's work is to assess this rate.
All women's consenting who had received conservative treatment at the sites identified since for more than 12 months were included in this multicenter cross-sectional study. The outcome measure was a recurrence of precancerous lesions of the cervix during visual inspection with acetic acid performed by a single practitioner to limit interobserver variability. Data collection and analysis were done on the Stata 13 software. We performed an univariate then multivariate analysis with logistic regression.
Two hundred and seventy-nine participated in this study with an average age of 37.44 (σ = 7.31 years). A total of 52.33% were HIV positive. Moreover, 63.44% were treated by cryotherapy versus 36.66% by loop electrosurgical excision procedure. The overall prevalence of recurrences was 8.96%. Multivariate analysis with logistic regression concluded that the risk of recurrence was 5.72 times (OR = 1.69–19.29; P = 0.005) higher with cryotherapy and 2.85 times higher (OR = 1.04–7.82; P = 0.042) in women with HIV.
The risk of recurrence is proportionally high with cryotherapy and HIV status. This suggests that an adaptation of the strict monitoring protocols to our African context due to the lack of cytocolposcopic logistical resources.
FAM19A4/miR124-2 methylation analysis as a triage test for HPV-positive women: cross-sectional and longitudinal data from a Dutch screening cohort
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The aim was to evaluate the cross-sectional and long-term triage performance of FAM19A4/miR124-2 methylation analysis in human papillomavirus (HPV)-based cervical screening.
We conducted a post hoc analysis within a Dutch population-based HPV-positive study cohort of women aged 30–60 years (n = 979). Cross-sectional cervical intraepithelial neoplasia (CIN) 3+ sensitivity, specificity, positive predictive value and negative predictive value as well as cumulative CIN3+ or cervical cancer risks after 9 and 14 years were compared for three baseline triage strategies: (1) cytology, (2) FAM19A4/miR124-2 methylation analysis and (3) combined FAM19A4/miR124-2 methylation with cytology.
CIN3+ sensitivity of FAM19A4/miR124-2 methylation analysis was similar to that of cytology (71.3% vs 76.0%, ratio 0.94, 95% CI 0.84 to 1.05), at a lower specificity (78.3% vs 87.0%, ratio 0.90, 95% CI 0.86 to 0.94). Combining FAM19A4/miR124-2 methylation analysis with cytology resulted in a CIN3+ sensitivity of 84.6% (95% CI 78.3 to 90.8) at a specificity of 69.6% (95% CI 66.5 to 72.7). Similar 9- and 14-year CIN3+ risks for baseline cytology-negative women and baseline FAM19A4/miR124-2 methylation-negative women were observed, with risk differences of –0.42% (95% CI –2.1 to 1.4) and –0.07% (95% CI –1.9 to 1.9), respectively. The 14-year cumulative cervical cancer incidence was significantly lower for methylation-negative women compared to cytology-negative women (risk difference 0.98%, 95% CI 0.26 to 2.0).
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Chapter 7: Achievements and limitations of cervical cytology screening

Abstract

Introduction

Section snippets

Pathogenesis of cervical cancer

Public health considerations

What makes a screening programme work?

Overview

Technology in cervical cytology

Conclusions

Disclosed potential conflicts of interest

Lancet

Lancet

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Prevent Med

Lancet

Effect of screening on incidence of and mortality from cancer of cervix in England: evaluation based on routinely collected statistics

BMJ

Global cancer statistics, 2002

CA Cancer J Clin

IARC handbooks of cancer prevention

Accuracy of the Papanicolaou test in screening for and follow-up of cervical cytologic abnormalities: a systematic review

Ann Intern Med

Interobserver reproducibility of cervical cytologic and histologic interpretations: realistic estimates from the ASCUS-LSIL Triage Study

JAMA

Cost-effectiveness of cervical-cancer screening in five developing countries

N Engl J Med

A randomized clinical trial of cryotherapy, laser vaporization, and loop electrosurgical excision for treatment of squamous intraepithelial lesions of the cervix

Obstet Gynecol

Surgery for cervical intraepithelial neoplasia

Cochrane Database System. Rev.