Cervical cancer is both a preventable and a curable
disease--preventable by cervical screening and curable, especially if identified at an
early stage. In developing countries, which lack screening programmes, the incidence may
be up to six times higher than in developed countries, with up to 80% of patients
presenting with advanced disease. The number of deaths from cervical cancer is estimated
to be more than 300 000 per year, and many of those who die are young mothers. Mortality
is highest in those countries least equipped to deal with the problem. But the reduction
of cervical cancer mortality in the developing world is only one of many priorities
competing for scarce funds. The current WHO recommendation is to evaluate visual
inspection to identify early curable cancer.1 A preventive strategy is more
constructive, but screening by cytology is too complex and expensive. Unaided visual
inspection has been assessed in four studies from India (table) and has been shown to have
a very low positive predictive value (PPV). Application of acetic acid (3-5%) to the
cervix is a routine part of colposcopy, and it turns CIN tissue white, which should enable
the detection of preinvasive lesions by the naked eye. An assessment of visual inspection
aided by acetic acid (VIA) is reported by Z M Chirenje
and colleagues in this issue of The Lancet.
In this study done in Zimbabwe, 10 934 women were screened by trained paramedical
workers, by VIA and by exfoliative cervical cytology. Women with abnormal results by
either test underwent colposcopy. To find out the true sensitivity, specificity, and PPV
for high-grade CIN, in the second phase of the study 2203 women underwent colposcopy
irrespective of findings on VIA or exfoliative cytology. The completion of such a
controlled study in an undeveloped setting is a substantial achievement, which provides an
important contribution to the assessment of this approach. The main findings of the study
were that VIA was abnormal in about 20% of women, and it had a PPV of 25·9%. Its
detection rate for CIN was similar to that for cytology. The second phase of the study
showed that VIA was more sensitive (76·7%) than cytology, but the PPV for the detection
of high-grade disease was only 18·6%. The relatively poor specificity of VIA (64·1%)
compared with cytology (90·6%) may have been affected by the very high rate of sexually
transmitted disease.
VIA therefore represents a proven, simple means of identifying women with CIN in
undeveloped health facilities, though the level of training is probably critical to the
success of VIA. The data from Zimbabwe compare very favourably with those from other less
controlled studies of VIA (table). VIA is not the only alternative to screening by
cytology. Tests for the detection of human- papillomavirus (HPV) DNA in the cervix can be
done on a mass scale. A heavy viral load or persistent infection is associated with either
an underlying CIN or its development in 4 years.7 In a screening study recently
reported from Costa Rica,8 over 70% of the identified CIN2/3 lesions were
associated with high-risk HPV types, but the age-related positivity rates varied from
18·5% (for women aged <25 years) to 5% (35-54 years). The specificity of HPV as a
screening test for high-grade CIN can be increased by identifying persistence over 12
months, but this approach is not as practicable as a single test in an undeveloped
setting. Restriction of this approach to women over the age of 35 years would improve
specificity. The efficacy and cost-effectiveness of HPV population screening is being
assessed in Sweden and the Netherlands, and other randomised controlled trials are
planned.
Could less complex screening strategies be implemented on a wide scale? The first key
element is specificity for the true precursor lesion, CIN3. The identification of large
numbers of women with low-grade CIN will not be cost-effective. The second problem is how
to treat CIN lesions on a large scale in undeveloped or remote areas. There are several
methods for destroying the lesion (see next commentary9), all of which except
cryotherapy require electric power for their use. Loop diathermy is simple and effective,
although cryotherapy is probably as effective and requires only compressed gas for
chilling of the cryoprobe. A test with a PPV of 25% means that three of every four women
would potentially be overtreated. However, in view of the low morbidity associated with
these treatments in well-trained hands, the treatment of the cervix in all women with
abnormal screen results could be judged to be ethical because of the huge reduction in
risk of cervical cancer so achieved, especially without the complexity of colposcopic or
other means of tissue diagnosis.
Screening should go hand in hand with health education, which is of proven value in
reducing the rate of deaths from cervical cancer.10 Making young women more
aware of their sexual health could help reduce not only the risk of cervical cancer but
also the risk of other sexually transmitted diseases. Perhaps the most exciting prospect
is a prophylactic HPV vaccine that could prevent infection and cervical cancer. Such a
vaccine would be a huge contribution to human health. Tackling cervical cancer in
impoverished countries with underdeveloped health-care systems seems a daunting prospect,
but Chirenje and colleagues and others have shown one way forward. Society should accept
the challenge of trying to reduce the global death rate from this devastating but
preventable disease.
References
- Cervical cancer control in developing countries: memorandum from a WHO meeting. Bull
World Health Organ 1996; 74: 345-51.
- Sehgal A, Singh V, Bhambhani S, Luthra UK. Screening for cervical cancer by direct
inspection. Lancet 1991; 338: 282.
- Singh V, Sehgal A, Luthra UK. Screening for cervical cancer by direct inspection. BMJ
1992; 304: 534-55.
- Nene BM, Deshpande S, Jayoant K, et al. Early detection of cervical cancer by visual
inspection: a population-based study in rural India. Int J Cancer 1996; 68:
770-73.
- Wesley R, Sankaranarayanan R, Mathew B, et al. Evaluation of visual inspection as a
screening test for cervical cancer. Br J Cancer 1997; 75: 436-40.
- Sankaranarayanan R, Wesley R, Somanathan T, et al. Visual inspection of the uterine
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precursors. Cancer 1998; 83: 2150-56.
- Kjaer SK, van den Brule AJC, Paull G, et al. Risk of incident cervical neoplasia in a
prospective cohort study from Denmark: positivity to identical HPV types at enrollment and
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Conference, Charleston, USA, Jan 9-15, 1999: 333.
- Lorincz AT, Hildesheim A, Herrero R, Mielzynska I, Sherman ME, Schiffman M. Comparison
of hybrid capture II HPV DNA detection and conventional Pap smear for cervical cancer
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Charleston, USA, Jan 9-15, 1999: 26.
- Cox TJ. Management of cervical intraepithelial neoplasia. Lancet 1999; 353:
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- Ponten J, Adami HO, Bergstrom R, et al. Strategies for global control of cervical
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The Lancet Journal Article |
