HPV & Cervical cancer - Screening

Screening for Cervical Cancer

Routine cervical screening, a form of secondary prevention, is currently the most successful way to identify pre-cancerous lesions and cervical cancer. Cervical screening programmes are in place in many countries.

In countries where organised screening programmes are widespread, screening can reduce the incidence of cervical cancer by approximately 80% (Schiller and Davies 2004).

Despite this, many women in countries with well-organised screening programmes still die from the disease every year (Anttila et al 1999; Franco et al 2001; Quinn et al 1999).

In most cases, however, the screening programme enables the identification of abnormal cells at an early stage.

In women undergoing regular cervical screening, the incidence of cervical cancer can be reduced by approximately 80% (Schiller and Davies 2004).

If cervical screening shows abnormal findings, this is an indication that pre-cancerous changes may be occurring within the cells of the cervix, and a number of follow-up procedures may be considered.

In most cases, the first diagnostic step will be a colposcopy – a visual examination of the cervix in which a trained colposcopist applies acetic acid to visualise any abnormalities and examines the cervix with a colposcope.

If the results of the colposcopy are inconclusive or suggestive of cervical abnormalities, a biopsy of the affected area of the cervix will then be performed. Depending on the results of the biopsy, treatment, if needed, can be scheduled.

Alternative forms of screening for cervical cancer are available and undergoing testing. They include oncogenic HPV screening, in which oncogenic HPV DNA is detected, usually by a test called Hybrid Capture II (developed by the Digene Corporation, Maryland, US) or the Amplicor HPV DNA test (Roche Diagnostics, Basle, Switzerland). Oncogenic HPV screening is best used as an adjunct to conventional cervical screening, although this procedure has not yet gained complete acceptance.

Another alternative is visual inspection with acetic acid (VIA) also known as ‘see and treat’. Visual screening is rapid and inexpensive but carries a high rate of false positive results (Jacob et al 2005).

Screening method

When is it used

Advantages

Disadvantages

Cervical screening: Pap smear

Ideally, every 2-3 years in all women aged 18-64 (Sawaya et al 2003; Taylor et al 2000)

Opportunistic screening can also be beneficial (Franco et al 2001)

Allows detection of abnormal cells, often before the development of invasive cervical carcinoma

Regular pap screening can reduce the incidence of cervical cancer by 80% (Schiller and Davies 2004)

Secondary prevention – does not prevent cervical dysplasia (Basen-Engquist et al 2003; Khanna and Phillips 2001)

Often unsuccessful and too costly in low-resource settings (Mandelblatt et al 2002; Sankaranarayanan et al 2005)

Risk of over-treatment and associated anxieties due to misclassification of results (false positives) (Condel et al 2002) and the likelihood of regression from mild dysplasia even without treatment (UK Government Statistical Services 2004)

Some cancers, particularly adenocarcinomas, may be missed (Renshaw et al 2004)

Cervical screening: Liquid-based cytology (LBC)

A modern alternative to the pap smear, LBC is most cost effective when carried out every 3-5 years in all women aged 21-64 (Karnon et al 2004)

As for pap smear, but:

Fewer unsatisfactory samples than with conventional pap smear (Hussein et al 2005)

As for pap smear

Colposcopy

Usually after ASC-H, LSIL or HSIL cervical screening result (Patnick 2000b)

Occasionally after ASC-US result, particularly in immunosuppressed women (Wright, Jr. et al 2003)

Quick, inexpensive procedure
Can allow simultaneous biopsy

Allows rapid detection of cervical abnormalities in women with abnormal screening results (Bolger and Lewis 1988)

Requires highly trained staff; prone to human error (Brotzman and Apgar 1998)
Potential for over-treatment, particularly after ASC-US or LSIL diagnosis (Wright, Jr. et al 2003)

Invasive procedure, associated with anxiety and non-adherence (Basen-Engquist et al 2003)

Biopsy: Cone biopsy / LEEP

After HSIL cervical screening test result, often as part of a colposcopy (Wright, Jr. et al 2003)

Can serve both as a diagnostic tool and as a treatment

Invasive procedure
Heat-induced damage can complicate analysis of LEEP-excised tissue (Chen et al 1994)

Requires complex equipment (Mandelblatt et al 2002)

Oncogenic HPV DNA testing

In women over 30 years old presenting with cervical dysplasia identified during routine cervical screening (Wright, Jr. et al 2003)

May be useful for triage of women presenting with ASC-US, can prevent over-treatment (Human papillomavirus testing for triage of women with cytologic evidence of low-grade squamous intraepithelial lesions: baseline data from a randomized trial. The Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesions Triage Study (ALTS) Group 2000; Wright, Jr. et al 2003), and reduce the associated costs (Goldie et al 2004)

Low rates of false negative results (Qureshi et al 2003)

High cost can be prohibitive (Mandelblatt et al 2002)
Cannot distinguish transient and persistent infections
Poor diagnostic value in young women, as HPV prevalence is higher than in older women (Human papillomavirus testing for triage of women with cytologic evidence of low-grade squamous intraepithelial lesions: baseline data from a randomized trial. The Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesions Triage Study (ALTS) Group 2000; Goldie et al 2004)

Positive test results are associated with anxiety and distress, but the majority of oncogenic HPV infections do not progress to dysplasia or cervical cancer (McCaffery et al 2004)

Visual inspection with acetic acid (VIA)

Screening of sexually active women, especially in low-resource settings (Blumenthal et al 2005; Sankaranarayanan et al 2005)

Relatively inexpensive (Mandelblatt et al 2002; Sankaranarayanan et al 2005)
Diagnosis and treatment take place in the same visit (Jacob et al 2005; Sankaranarayanan et al 2005)
Training can be accomplished in a short period of time (Blumenthal et al 2005)

Requires few consumable supplies (Jacob et al 2005)

High level of positive results can lead to significant over-treatment (Jacob et al 2005)
Associated with pain and discomfort, particularly during cryotherapy (Jacob et al 2005)

Ablative procedure; no tissue is available for analysis (Jacob et al 2005)

Overview of screening methods

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