Colposcopy
INTRODUCTION ¡@

History of the Procedure: Literally translated, colposcopy means “to look into the vagina?(colpo = vagina, scope = to look). Colposcopy was first described by Hans Hinselman of Germany in 1925. At the time he hoped this would be an effective screening tool for cervical cancer, one of the most common malignancies to afflict women in his era. Hinselman suspected that endophytic or exophytic lesions of the cervix were likely precursors of cervical carcinoma, and he hoped that by magnifying these tissues, precursor lesions might be identified early enough to allow effective treatment before invasive disease developed or spread. His theories on the genesis of cervical cancer were incorrect, and his protocol for colposcopic evaluation was clinically impractical, so the search for alternative methods for cervical cancer screening continued.

By the early 1940s, George Papanicolaou demonstrated the potential of cytologic screening (the Papanicolaou or Pap smear) as a test for malignant conditions of the cervix. At this point, colposcopy became a competing test with the Pap smear for cervical cancer screening. The Pap smear quickly demonstrated its superiority as a screening test and became widely accepted as the first-line modality for this purpose. The colposcope essentially was forgotten until the 1960s, when it was rediscovered as a complementary test for women with abnormal cytologic findings. Currently it enjoys near-universal acceptance as the most effective follow-up test for women suspected of having cervical lesions with malignant potential.

Problem: From the 1940s to the early 1970s, the common protocol for cervical cancer screening was for most abnormal Pap smears to be “treated?by cone biopsy of the cervix. Pathologic evaluation of these tissue specimens made it clear that most abnormal smears were associated with minor epithelial changes that had a low likelihood of malignant transformation. It was clear that this systematic overtreatment was unacceptable for reasons of cost as well as surgical and later pregnancy complications occurring in the typically young, healthy women on whom the procedure was performed. Inserting colposcopic evaluation as an intermediate step in this protocol quickly became accepted as a way to identify women truly in need of surgical therapy. This has dramatically reduced the number of unnecessary cone biopsy procedures and also has allowed for a more adequate delineation of lesions where surgical therapy remains appropriate.

Frequency: The importance of accurate screening and evaluation for cervical cancer cannot be overstated. At the turn of the last century, cervical cancer was the most common cancer to afflict women worldwide, as well as the most common malignancy among females in the US. Due mainly to the widespread implementation of effective screening programs (ie, Pap smears) the frequency of this cancer has decreased dramatically in the US. Still, an estimated 15,000 new cases occur per year in this country with approximately one third of that number being the cause of death each year. Additionally, 45,000 cases of high-grade premalignant cases are detected. Outside the US, especially in developing countries, the prevalence of cervical cancer remains high. At the end of the 20th century, it remained the second most common cause of cancer death in women worldwide.

Etiology: It is widely accepted that a critical factor in the development of the vast majority of cervical cancer is the acquisition of a virus that facilitates the change of normal cervical epithelium to dysplastic and, ultimately, malignant tissue. The virus implicated in this process actually is a family of viruses known as the human papillomavirus (HPV). There are 70-80 known types of these viruses, each with a different potential to cause malignant transformation. A small number of these viral types appear to have a strong predilection towards malignant change. These viruses typically are acquired through sexual contact, making cervical cancer in the eyes of some a type of venereal disease. In the US, estimates are for 2-3 million new cases of HPV infection each year. By cytologic examination, as many as 3% of women in the US are found to have evidence of HPV at any given time. This testifies to the conceivably enormous spread and propagation of this potentially devastating disease.

INDICATIONS ¡@

Any time a malignant lesion or precursor is suspected in the cervix, vagina, or vulva, this is an indication for colposcopic testing. As mentioned earlier, the most common reason for performance of a colposcopy is in the evaluation of a woman with an abnormal Pap smear. Currently, almost all pathology laboratories utilize the Bethesda system for reporting findings of cervical cytology. The major categories in this system are listed below.

The Bethesda System for reporting Cervical Cytologic Diagnosis

Approximately 90% of cervical carcinomas are of the squamous variety. Progression of cervical dysplastic change to carcinoma occurs in a predictable pattern. The latent period between infection with an oncogenic HPV virus and demonstration of Pap smear abnormalities can be measured in years. Once dysplastic changes are initiated, the degree of dysplasia typically slowly worsens as the cellular changes progress towards carcinoma. Squamous cells first become atypical then demonstrate low-grade dysplastic changes followed by high-grade changes and, ultimately, cancer develops. Spontaneous resolution of lesions at each level of dysplasia has been demonstrated, but this becomes less likely as severity increases. Rapid progression of dysplastic lesions to invasive cancer also has been described; therefore, all irregularities should be evaluated, with a treatment plan developed in an expedient fashion.

Colposcopy is ideally suited to help accurately evaluate lesion severity so that an appropriate treatment plan can be instituted.

Most practitioners recommend colposcopic evaluation for all women with Pap findings of HGSIL or worse. There is no consensus on the need for routine colposcopy for patients with a single ASCUS or LGSIL result. Currently, most women in the US with a LGSIL report are triaged for colposcopic evaluation. The appropriateness of this strategy has never been definitively established, and certainly the chances of finding an invasive cancer in this setting are very small.

In a low-risk population, no more than 5% of Pap smear reports should feature ASCUS. Many practitioners choose to have those patients with ASCUS findings simply undergo a repeat screening test within 6 months. Those with persistent higher-level irregularities then are triaged for colposcopy. On the other hand, it is not uncommon among individual practitioners to perform colposcopy for all women with ASCUS findings. Patients with clinically visible lesions of the cervix should undergo colposcopy regardless of the results of cytologic screening. Pap smears are known to have a significant false negative rate (as high as 15%), so all clinically apparent irregularities should be carefully evaluated to avoid neglecting potentially invasive lesions.

RELEVANT ANATOMY AND CONTRAINDICATIONS ¡@

Relevant Anatomy: The minimum goal of every colposcopic procedure should be to rule out the presence of invasive cancer. In order to do this, the clinician must have an appropriate understanding of the anatomy of the cervix, with particular emphasis on the area where cancer is likely to occur, the transformation zone (TZ). Approximately 90% of cervical carcinomas occur in this small anatomic region. The TZ typically is a 2-6 mm band of epithelium around the external cervical os. It is an area of active cellular change from single-layer columnar epithelium to multilayered stratified squamous epithelium. Malignancies arising in this area tend not to extend past the borders of the original squamocolumnar junction, making their identification on the portio of the cervix consistently feasible.

Malignant and premalignant conditions tend to display predictable visual patterns under certain conditions and when viewed under magnification. Recognition of these patterns is the basis behind colposcopic evaluation and diagnosis. To appreciate and reliably identify patterns associated with these lesions, an understanding of normal patterns first must be acquired.

The cervix displays the boundary between stratified squamous epithelium, which is contiguous with that lining the vagina and columnar epithelium that is contiguous with that lining the interior of the upper reproductive tract. This interface is called the squamocolumnar junction. It can be seen on the external face of the cervix in greater than 70% of menarchal girls. Over time, this interface gradually moves inward toward the external os. The area between its initial largest circumference and its current position at any time is known as the transformation zone. This is an area of dynamic cellular activity and change. At puberty and again during an initial pregnancy, this cellular activity appears to be accelerated.

The physiologic changes of puberty, especially the decreased environmental pH, cause the exposed columnar epithelium to undergo a change known as metaplasia. In this process a new type of cell, the reserve cell, appears beneath the simple columnar cells. The endocervix has a pseudovillus structure that actually is a complex infoldings of the epithelium. The process of metaplasia tends to begin at the tips of these fronds with extension to the bases or coalescence of areas in close proximity to each other to obliterate the intervening clefts. These reserve cells undergo morphologic change and ultimately cause sloughing and disappearance of the overlying columnar epithelium. They further undergo a maturation process that ultimately leaves them indistinguishable from the adjacent stratified squamous cells.

These cell types have a different reaction to the application of dilute acetic acid. The reactions can be seen under magnification if light is then shone on the tissue. Dilute acetic acid (3-5%) effectively removes the thin mucous covering of the epithelial surface. It further penetrates into the surface cell causing coagulation of intracellular proteins and dehydration of the intracellular compartment. These actions essentially make the cells more refractory towards light, as there is less space between nuclei and their surrounding proteins for light energy to pass through. As a result, more light is reflected back toward its source, changing the perceived color of the area in view. Areas where light is more heavily reflected take on an obvious whitish coloration and are described as acetowhite epithelium.

If light is shone on normal cervical epithelium after the application of dilute acetic acid, characteristic appearances can be noted. The cells of the stratified squamous epithelium typically are 20-30 cells in depth. The cells near the surface are flat and elongated, with very small nuclei. They have a large amount of glycogen in their cytoplasm. Acetic acid applied to this tissue has little effect on the cells physical state, and the solution cannot penetrate to the deeper cell layers where its effect would be more apparent. The appearance of this portion of the cervix when viewed under magnification essentially is unchanged from its appearance prior to the acetic acid application.

Most of the light still can pass easily through the surface cells, and only a minimal amount of light is reflected back . This tissue appears as a homogenous pinkish-tan color. Blood vessels are not readily apparent in mature estrogen-primed tissues as they are beneath the 20-30–cell layer. When vessels are seen, they tend to be of small and diminishing caliber running parallel to the surface.

The normal columnar epithelium medial to the squamous tissue appears in sharp contrast. Since this tissue is only a single cell layer thick, light transmits easily through it even though the nuclear-to-cytoplasmic ratio is greater than in the surface squamous cells. Since the tissue is so thin, the underlying vasculature is in close proximity, and light is heavily absorbed in the red spectrum of blood. This tissue therefore appears a bright red color because of minimal reflectance and maximum absorption in the red spectrum.

The process of metaplasia always is present to some degree at the squamocolumnar junction. The cells undergoing this metaplastic process are characterized by relatively large nuclei and proteinaceous cytoplasms. Application of an astringent agent such as acetic acid, with its above-referenced cellular effects, makes these cells denser and more reflective of light. With more light reflected back towards its source and less being absorbed, the tissues take on a whitish-grey appearance. This change appears filmy or thin through the colposcope because of the thinness of the metaplastic layer of cells.

Cells infected with certain types of HPV undergo morphologic changes that result in relatively large nuclei that are surrounded by viral proteins. Depending on viral type and duration of infection, these changes eventually can encompass the entire thickness of the maturing squamous epithelium. Following acetic acid priming, light that shines on these tissues will penetrate poorly, with most being reflected back.

Therefore, tissues with extensive HPV involvement appear notably white compared to their surrounding tissues. HPV-infected cells can in many cases become significantly altered to the point of losing their normal structure and becoming dysplastic. As this progresses, the full thickness of the squamous epithelium becomes composed of larger rounder, cells with larger nuclei than would be expected in normal tissue. Because of this nuclear density, which is further increased after acetic acid exposure, light is heavily reflected and minimally absorbed, again giving a white color compared to surrounding normal tissue.

Once significant experience is acquired, differentiating the appearance of normal from HPV-infected or dysplastic tissue becomes relatively straightforward. The major difficulty lies in distinguishing between high-grade dysplasia and invasive changes from those of simple HPV infection. This differentiation is critical as one has a significant potential for malignant transformation while the other commonly is self-limited. To be able to reliably discern between these, an appreciation for the colposcopic appearance of blood vessel patterns present in these lesions becomes critical. Each of the villous fronds that protrudes upward in the columnar lined endocervix has its own capillary supply. As metaplasia replaces this tissue with stratified squamous epithelia, these vessels typically regress and no longer are apparent colposcopically.

This metaplastic epithelium appears particularly susceptible to infection by the HPV viruses. If infected, the normal maturation process can be disrupted not only in the epithelial cells but in the underlying vessels as well.

When dysplastic change occurs in these tissues, the subepithelial vessels persist in a perpendicular course to the surface of the tissue. As the process proceeds in severity, vessels actually can grow into the epithelium itself. Because of their perpendicular orientation, these vessels are visualized under magnification in an end-on fashion. They appear as red dots in the acetowhite epithelium. This is known as a punctate pattern or as punctation. These vessels also can become interconnected in intricate patterns so that when viewed under magnification their interconnecting courses parallel to the surface can be seen. These connections form random patterns that when viewed under magnification appear as red lines. These lines form patterns reminiscent of a tiled walkway and are referred to as mosaic patterns or mosaicism .

These vascular patterns are critical in evaluation of lesion severity through the colposcope. Either punctation or mosaicism can be seen in high-grade or invasive lesions. It does not appear that there is a predictable progression from one to the other as lesions increase in severity. In fact, they frequently appear together in the same lesion.

However, some suggest that characteristics of either pattern can be predictive of lesion severity. Specifically, the caliber and spacing of the vascular patterns appears predictive of lesion severity. Wide caliber or widely spaced (ie, greater than 200 microns or 0.2 mm) vessels tend to occur in in-situ or invasive lesions. Patterns of vessels with smaller caliber and regular, close spacing are typical of lesions with lesser degrees of dysplastic change. The presence of irregular vessel course also is predictive of lesion severity. Sudden vessel termination, hairpin or comma-type turns of vessels, or enlargement of a previously diminishing caliber all are suspicious for malignant transformation.

Contraindications: There are no absolute contraindications to the performance of a colposcopic exam. The patient’s ability to tolerate a standard speculum examination is the only true limiting factor. Active cervicitis should be treated before undertaking the exam as inflamed tissues can alter the ability to obtain an accurate assessment and also can make the discomfort of the exam markedly worse.

WORKUP ¡@

Diagnostic Procedures:
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TREATMENT ¡@

Surgical therapy: Following accurate colposcopic evaluation of a cervical lesion, appropriate treatment then can be tailored to the individual patient's needs. Treatment options include conservative follow-up with cytology, ablation with cryotherapy or laser, excision with LEEP or cold knife cone, and hysterectomy for invasive lesions. Regardless of treatment undertaken, plans for follow-up screening should be stressed to evaluate for recurrent or residual disease.

Another circumstance where colposcopy has proven to be of great benefit is in the evaluation of the pregnant patient who has an abnormal Pap smear. Prior to the use of colposcopy in this setting, cervical disease could be treated only via cone biopsy. In pregnancy, this can be a difficult and frightening procedure. Excessive bleeding is very common due to the increased vascular supply to these tissues during gestation. The procedure also is associated with a significant fetal loss rate.

Colposcopic examination actually is well suited for pregnancy. The normal cervical enlargement of pregnancy causes eversion of the transformation zone farther onto the face of the cervix, making adequate visualization a relative certainty. Biopsy of the cervix can be done in pregnancy and should be performed for any lesion suspected of being invasive. Bleeding from even small biopsy sites can be brisk and persistent, so special preparation for this likelihood should be undertaken. While positioning the biopsy forceps to obtain a sample, a cotton swab saturated with Monsel paste should be readied immediately adjacent to the instrument. As soon as the biopsy is taken, and before removal of the specimen, the swab should be firmly applied to the wound bed. A large second swab should be ready to put in place after removal of the first. With this small modification, bleeding seldom is a significant problem. If it still does occur, preparation for placement of a small suture should be immediately available.

COMPLICATIONS ¡@

Complications from colposcopic procedures are exceedingly rare. Occasionally, bothersome bleeding can occur following biopsy. This tends to be problematic only with procedures performed during pregnancy or with large excisional procedures. Infection of biopsy sites also is exceedingly rare, although it can occur following laser ablation or LEEP procedures. The most worrisome complication is inadequate or inaccurate evaluation leading to the missed diagnosis of invasive cancer. This obviously can lead to treatment delays and poorer outcomes. Another complication is the overestimation of lesion severity by inexperienced practitioners. This can put the patient in a treatment course that may not be necessary and has the potential for adverse sequelae. Many of these sequelae center around future fertility limitations such as cervical stenosis or incompetence.

This infrequent but preventable lack of adequate evaluation is the only real controversy surrounding the procedure today. Simply put, the question is who should be performing the exam and what training requirements must be met before instituting the procedure on patients. Because of the prevalence of HPV disease and the frequency of abnormal Pap smears, this becomes both an economic and quality issue. Some have recommended 200 supervised procedures to gain competence followed by regular performance of at least 25 procedures a year to maintain competence. The learning curve undoubtedly is practitioner-dependent, and currently no adequate studies have identified minimum criteria for certification. All practitioners performing this procedure should put mechanisms in place to ensure their own competence and safety.

FUTURE AND CONTROVERSIES ¡@

The colposcope also can be helpful in evaluating lesions of the vagina or vulva. The vaginal epithelium essentially is identical to that of the exocervix. Acetowhite changes and vascular patterns can be seen that are similar to those found described on the cervix. Since vaginal lesions do not originate in metaplastic tissue, the vascular patterns previously described are not as reliable a finding. Biopsies should be performed routinely on all acetowhite areas. The vagina is more sensitive to pain than the cervix, so these biopsies should be done with local anesthetic coverage.

The vulva can develop squamous malignancies as well, although less commonly than the cervix. These tissues also can show acetowhite changes, but because of the thickness of the epithelium and its keratin surface, acetic acid should be applied for a greater length of time and in a higher concentration (eg, 5%) to be effective in bringing about this change. Vascular patterns are less commonly present in these tissues, but when they are seen biopsies should be performed liberally. Again, because of the sensitivity of these tissues, all biopsies should be done under local anesthetic.

Another utilization of the colposcope is in the evaluation of the sexual assault victim. This has gained popularity, especially in the evaluation of children suspected of being assaulted. The low magnification of the colposcope can assist in identifying tissue trauma that might be too subtle to be detected by the naked eye. Careful, thorough, and gentle examination, especially of hymenal tissues, usually can be accomplished with minimal discomfort. Attached cameras for recording findings can be especially helpful from an evidentiary perspective.

BIBLIOGRAPHY ¡@