Screening for Human Papillomavirus Infection

Prepared by J. Kenneth Johnson, MD, Research Associate, Department of Preventive Medicine and Biostatistics, University of Toronto, Ontario



Objective
To make recommendations about screening for human papillomavirus (HPV) infection in asymptomatic women in Canada. HPV infection has been associated with increased risk for and grade of cervical cancer.

Burden of Suffering
Much of the epidemiology of human papillomavirus (HPV) remains to be determined, and precise estimates of incidence and prevalence are not available, since HPV commonly exists in a subclinical form. Of the over 60 separate serotypes that have been identified to date, HPV-16 and HPV-18 are most closely associated with risk for genital cancers. A large Canadian study of a screening program for cervical cancer in the late 1970s showed that 1.69% of 234,715 women had signs of cervical HPV on cytological examination. In a population-based study of 63,115 Finnish women aged 20-65 years, the estimated lifetime risk of infection with HPV was calculated to be 79%.

In Canada in 1993 approximately 1,300 new cases of invasive carcinoma of the cervix were diagnosed, and about 400 deaths were expected to occur from this disease. The yearly overall cost of invasive disease and death in Canada from cervical cancer has been estimated at 180 to 270 million dollars.

Options
Main screening options were visual inspection, Pap smear, colposcopy/cervicography, HPV group-specific antigen, DNA probe, dot blot or Southern blot, or polymerase chain reaction. Treatment options included physical or chemically destructive agents (conization, cryosurgery, lasers, salicylic acid, cantharidin, bi- and trichloroacetic acid) and chemotherapeutic agents (podophyllin, 5-fluorouacil, bleomycin).

Outcomes
Test sensitivity and specificity; cure (e.g., complete clearing of warts) and recurrence rates.

Evidence
MEDLINE was searched for 1966 to June 1993 using the keywords "papillomavirus", "cervix neoplasms", "mass screening", "prospective studies", "prevalence", "sensitivity", "specificity", "human", and "female".

Values
The 13-member Task Force of experts in family medicine, geriatric medicine, pediatrics, psychiatry and epidemiology used an evidence-based method for evaluating the effectiveness of preventive health care interventions. Recommendations were not based on cost-effectiveness of options. Patient preferences were not discussed.

Background papers providing critical appraisal of the evidence and tentative recommendations prepared by the chapter author were pre-circulated to the members. Evidence for this topic was presented and deliberated upon in 1- to 2-day meetings, 2 to 3 times per year from January 1993 to June 1993. Consensus was reached on final recommendations.

Benefits, Harms, and Costs
In general, available tests have poor sensitivity and specificity, and are invasive and costly. Test characteristics are summarized below.
 

Test
Sensitivity
Specificity
Visual inspection
high
low
Pap smear
15%
(range of 19% to 52%)
--
(50% in one study)
Colposcopy
100%
10% - 20%
Group-specific antigen
--
low specificity
Hybridization techniques
poorly defined to date
poorly defined to date
Polymerase chain reaction
extremely sensitive
(significant false positive rate)
--

The natural history of HPV is not well understood. Comparison between studies is difficult because of differences in reported outcomes. An RCT of Podophyllotoxin therapy reported complete clearing of penile warts in 53% of 34 patients, but 100% recurrence in patients who returned for 16 week follow-up. Most studies with sufficient follow-up report high recurrence rates. RCTs with interferon and CO2 laser vaporization found better cure rates. However, recurrence rates remained high, and good cure rates were also found in untreated patients. Currently, no therapy exists for latent HPV infection. Thus, the value of screening is unknown. Potential adverse effects of screening include test- and treatment-related morbidity, labelling, increased costs and therapeutic load.

Recommendations
Recommendation grade [A, B, C, D, E]  and level of evidence [I, II-1, II-2, II-3, III] are indicated after each recommendation. Citations in support of individual recommendations are identified in the guideline text.

Validation
This report was externally peer-reviewed. The recommendation is consistent with that of a 1989 Canadian workshop on cervical cancer screening.

Sponsors
The Canadian Task Force on Preventive Health Care developed this guideline with funding from Health Canada.

Source Document
Johnson J.K. Screening for human papillomavirus infection. In: Canadian Task Force on the Periodic Health Examination. Canadian Guide to Clinical Preventive Health Care. Ottawa: Health Canada, 1994; 768-76.