An abnormal cervical smear. Now what?

Colposcopy provides additional information

“Not every woman who tests positive for high-risk HPV is referred for a colposcopy, because otherwise I’d be performing colposcopies from morning to night without finding many serious abnormalities,” Dr Dewilde says with a smile. “That is why triage is needed. In the new Belgian screening approach, this is done through cytology, although other tests also exist, such as dual staining and, soon, methylation testing (see Box). There are extensive tables, based mainly on international data, that estimate the statistical risk of a precancerous cervical lesion for different combinations of cytology results, HPV type and age. On that basis, we made a choice, because you don’t want to subject too many women to a colposcopy, and possibly a biopsy or treatment, when the likelihood of an abnormality is extremely small. In Belgium, as in most other European countries, we have decided to perform a colposcopy when the risk of a precancerous cervical lesion is 10% or higher. It is, in essence, a diagnostic tool to establish whether a lesion is there or not.”

How is a colposcopy performed? It is an examination in which the cervix and vagina are inspected using a special microscope called a colposcope. The procedure takes place during a regular consultation. As with a cervical smear, a speculum is inserted into the vagina. The colposcope allows the doctor to detect abnormalities that are often invisible to the naked eye. To make them easier to see, the cervix is dabbed with solutions such as acetic acid and iodine, causing any abnormal cells to show up more clearly. During the examination, digital images are taken and, if necessary, the doctor collects a smear sample or a biopsy for further analysis. A biopsy can sometimes cause some pain or discomfort. The entire examination usually takes five to ten minutes. Examination of the tissue will determine whether any lesion is low-grade or high-grade (see Box).

“In Belgium, as in most other European countries, we have decided to perform a colposcopy when the risk of a precancerous lesion reaches 10%.”

Follow-up remains important

“Persistent high-risk HPV infections increase the risk of precancerous lesions and cervical cancer, but some women continue to test positive without ever developing a lesion,” says Dr Dewilde. “Because we currently cannot predict who will and will not develop a lesion, we treat a detectable virus as a risk factor. That is why annual follow-up is recommended even after a colposcopy that shows no high-grade lesion — usually with an HPV test. If that test is negative, we repeat it after one year; if it remains negative, you can return to routine screening. If the virus is still present, a colposcopy is always performed for HPV types 16 and 18. For other high-risk types, cytology is carried out first: if high-grade abnormalities are found, we repeat the colposcopy; if the findings are normal or low-grade, we continue annual follow-up with an HPV test. As long as that test remains positive, we repeat the colposcopy every two years, and sometimes even annually — if the transformation zone, the relevant area of the cervix, is less clearly visible.” (See Box)

“With very long-standing infections, we sometimes choose to deviate from the general guideline,” he adds. “Guidelines are evidence-based and apply to most situations, but sometimes the approach needs to be tailored to the individual risk and discussed with the patient. For one person, a 5% risk is very high; for another, it means there is a 95% chance that nothing will happen. We discuss that together and decide on the next steps accordingly. So yes, you can sometimes depart from the guidelines — but only thoughtfully, with proper documentation, and only if you have sufficient expertise.”

Precancerous lesions can be treated

Cervical cancer develops slowly. On average, it takes at least 10 to 15 years for a precancerous lesion to progress to cancer. Dr Dewilde explains: “That is actually an advantage, strange as it may sound, because the process is so slow that periodic screening gives us multiple opportunities to detect these precancerous lesions and treat them in a simple, minimally invasive way, long before cancer develops.”

Precancerous lesions are removed through a cone biopsy—a procedure in which a cone-shaped piece of cervical tissue is removed, hence the name. [2]  Several techniques can be used to remove precancerous lesions, but the standard treatment in Belgium is large loop excision of the transformation zone (LLETZ), also known as loop electrosurgical excision procedure (LEEP). This treatment, performed under local or general anaesthesia and taking about fifteen minutes, is similar to a colposcopy: while viewing through a colposcope, the doctor uses a thin electrified wire loop to remove the abnormal area from the surface of the cervix. In this way, the entire area where the virus is active is removed, after which the tissue is sent to a pathologist for microscopic examination.

The Dutch guideline also mentions treatment with a vaginal cream, imiquimod, but this is preferably used in a research setting and only in specific cases.

“Not every precancerous lesion progresses to cervical cancer,” says Dr Dewilde. “Grade 2 lesions can disappear spontaneously, particularly in young women. Grade 3 lesions carry a clearly increased risk of malignant progression, although spontaneous regression is not unheard of. However, because we currently cannot predict which of these Grade 3 lesions will regress and which will not, we generally treat them all because of the increased cancer risk.”

This approach is also informed by lessons from the past. In New Zealand, between 1955 and 1976, a large group of women with Grade 3 lesions were not treated because of the belief that CIN3 was not a true precursor of cancer. Years later, a study based on their medical records showed that a substantial proportion of them—between one-third and one-half—ultimately developed cervical cancer. “That is exactly what we want to avoid,” he emphasises. “In the future, new techniques such as biomarkers or methylation testing may allow us to better identify which lesions can safely be monitored, but for now, when it comes to CIN3, we do not take risks and we treat.” 

There is no treatment for HPV

Would it not be simpler for women who do not want (any more) children to have the uterus removed altogether? “I get that question quite often,” he replies. “But it is a major misconception that a radical hysterectomy is an adequate solution. While it does eliminate the risk of cervical cancer, that benefit does not outweigh the risks of the operation. Serious complications are rare, but they do occur, so there needs to be a very good reason to operate. More importantly, it is not a definitive treatment for HPV: if the virus remains present, lesions can still develop in the vaginal vault, the upper part of the vagina, even after a hysterectomy. It is also important to realise that HPV can cause cancers of the vagina, vulva, anus and throat, in addition to cervical cancer.”

Dr Dewilde is aware that it is not a popular message, but despite all the tablets and creams marketed for the purpose, the bottom line is simple: there is currently no treatment for an HPV infection. 

Stop burying your head in the sand!

Prevention therefore remains better than cure. For Dr Dewilde, the priorities are straightforward. “We need to vaccinate as many young people as possible against HPV, ideally through large-scale vaccination in the first year of secondary school, and we need to keep encouraging women to attend screening every three or five years. And who knows,” he says, “perhaps for women who have been vaccinated, it will soon be enough to test them only once or twice in their lifetime. They are much better protected, which means the risk of abnormalities is much lower. That is something currently being investigated.”

And what about women and their partners? What else can they do themselves? Dr Dewilde is unequivocal: “Talk about it! HPV, cervical cancer, cervical screening—talk about it with each other, with family, with friends. Make it less of a taboo subject. I often hear from patients that after receiving an abnormal smear result and being treated for a precancerous condition, they talk to friends who have never been screened, and that those friends then decide to get screened. That is a good thing. Any way of increasing participation, reducing ignorance and removing the taboo around the subject is worthwhile. Fear of a GP or gynaecologist appointment should never be a reason to put off screening. In most cases, it turns out to be much less daunting than expected. Find a doctor who makes you feel comfortable, ask questions, and bring someone along if that helps. But don’t put it off—burying your head in the sand always comes back to haunt you!”

[1] Every year, almost 9,000 women undergo a cone biopsy to treat precancerous lesions. Source: INAMI-RIZIV
[2] A cone biopsy is not only performed as a treatment, but is sometimes also used to help establish a diagnosis.

“Fear of a GP or gynaecologist appointment should never be a reason to put off screening.”