Cervical Cytology Screening And Evaluation
Clinical Expert SeriesCervical Cytology Screening and EvaluationKenneth L. Noller,MDFor nearly 50 years, the gynecologist’s mantra hasbeen “Yearly Pap and Pelvic.”1 Yet, it remains unclear how the practice of annual cytology became a defacto standard in the United States, because therenever has been an organized, national screeningprogram. I suspect that the test became an annualritual for many women as a result of the widespreaduse of oral contraceptives in the 1960s and 1970s andthe need for an annual examination to obtain prescription refills. However, now there is evidence that,for some women, annual cervical cytology screeningis both not necessary and may even lead to unnecessary morbidity.2Although the conventional Pap test is the bestcancer-screening tool ever developed—it has reducedthe incidence of invasive cancer of the cervix byapproximately 70%—multiple publications have documented the fact that the test is insensitive andsomewhat nonspecific. The reason that it is so effective in reducing cancer is a result of the natural historyof the disease, rather than the ability of a singlecytology sample to detect abnormalities. In addition,there are good data to support the fact that we havebeen far too aggressive in our management of womenwith minimal disease (ie, cervical intraepithelial neoplasia grade 1 [CIN 1]).Several national organizations, including the American College of Obstetricians and Gynecologists, theAmerican Cancer Society, the American Society ofColposcopy and Cervical Pathology (ASCCP), and theU.S. Preventive Services Task Force, have reviewed theextensive literature that has been published about Paptests and early lesions and have developed new guideFrom the Department of Obstetrics and Gynecology, Tufts University School ofMedicine and Tufts-New England Medical Center, Boston, Massachusetts.Corresponding author: Kenneth L. Noller, MD, Department of Obstetrics andGynecology, Tufts University School of Medicine and Tufts-New EnglandMedical Center, Boston, MA 02111; e-mail: knoller@tufts-nemc.org. 2005 by The American College of Obstetricians and Gynecologists. Publishedby Lippincott Williams & Wilkins.ISSN: 0029-7844/05VOL. 106, NO. 2, AUGUST 2005lines for the use of Pap test screening, the evaluation ofabnormal results, and management of low-grade cervical neoplasia.3–5In this article, I will explain how I have incorporated some of the new guidelines into my practice,how the use of the human papillomavirus DNA(HPV-DNA) test can help us manage patients, andhow I approach minimally abnormal cytology andbiopsy (CIN1).CYTOLOGY SCREENINGBecause the literature (and the Food and Drug Administration) supports the concept that liquid-basedcervical cytology screening can identify a few morecases of high-grade intraepithelial lesions (HSIL) thanconventional testing, the majority of practices havechanged to the liquid-based cervical cytology technique. In a woman who is being tested every year,there is no evidence that there is any clinical benefit,though. Probably the biggest advantage of liquidbased cervical cytology is that the same sample can beused for HPV-DNA testing, and some sexually transmitted disease testing.Our laboratory moved to the liquid-based technique a few years ago, so I use it. However, I wouldhave had no problem continuing to use the conventional technique for those women who are beingscreened yearly. It is a poor idea, though, to try to usedifferent techniques for different women, becausethere is an increased risk that mistakes in labeling andcollection will occur. My advice is to use 1 techniqueand to stick with it. In most offices that test will beliquid-based cervical cytology.Between 1980 and 2003, all of the national organizations that took a position on cytology screeningagreed that Pap testing should begin at age 18 years orat the onset of sexual activity. These same groupshave now changed that guideline and recommendstarting either at age 21 years or within 3 years of theonset of sexual activity.The reason behind the change is that mostwomen (and men, of course) become infected withOBSTETRICS & GYNECOLOGY391
HPV when they become sexually active.6 If a Pap testhappens to be taken while the infection is in its activephase, the report will indicate that changes consistentwith a low-grade squamous intraepithelial lesion(LSIL) are present, and if a biopsy is taken, it will beinterpreted as “mild dysplasia” or “CIN 1.” Becausemore than 70% of these infections clear spontaneously, it is better NOT to know about these infections:the patient will not worry, and the clinician will notfeel obliged to perform colposcopy, biopsy, and treatment.7,8 Indeed, 1 of the strongest reasons for thischange was the hope that far fewer young womenwould be treated for what is almost always a transientinfection.8Although I understand the motivation behind thischange, I believe that the more proper approachwould have been to educate physicians not to react toa minimally abnormal Pap test report. Even thoughthere is no particular reason to perform a Pap test ona newly sexually active woman, the same womandoes need contraceptive counseling and sexuallytransmitted disease counseling and testing. She needsto be encouraged to see someone who will addressthese issues, and that person is often her gynecologist.The guideline is also often misinterpreted tomean that Pap tests should not be performed until awoman is aged 21 years. That is not true. Rather, thefirst test should be performed within 3 years of theonset of sexual activity. Thus, the female who beginscoitus at age 15 should be regularly screened whilestill a teenager.In the 1980s many guidelines also recommendedthat yearly Pap testing was not necessary after severalnormal tests if the woman was at “low risk” forcervical cancer. That recommendation never caughton. Most of us continued to perform Pap testingannually.1 Perhaps the biggest reason we did so wasthat we could never identify, with any certainty, a“low-risk” population. The definition of “low risk”was a woman who began intercourse after age 18 (or21), had only 1 lifetime sexual partner, and thatpartner never had another partner. Only a smallnumber of women—fewer than 20%—fit this definition.9 In short, the recommendation to screen basedon sexual history did not work and has now beendiscarded.There are only 3 factors that have been shown tobe associated with cervical neoplasia that we caneasily use in our offices.3 Women with a prior historyof HSIL are at increased risk. So are women who areimmunosuppressed for any reason. Renal transplantation is one of the biggest contributors to this category (Fig. 1). Finally, women who were exposed todiethylstilbestrol before birth remain at higher risk ofdeveloping adenocarcinoma of the vagina at any age,392NollerCervical Cytology Screening and EvaluationFig. 1. Colpophotograph showing persistent human papillomavirus infection in a 31-year-old woman who hadundergone renal transplantation.Noller. Cervical Cytology Screening and Evaluation. ObstetGynecol 2005.and cytology may identify early lesions, even thoughmost are identified by palpation rather than by cytology. The new guidelines suggest that these 3 groups ofwomen continue to have annual cytology screening.Women who are human immunodeficiency viruspositive deserve special attention. With the advent ofmore and better therapies, the life spans of compliantwomen are now close to the general population. Forthese women, however, annual screening is still recommended. Abnormal cytology of any degree is bestevaluated by colposcopy.Perhaps the best way to determine who needs aPap test is to remember why we perform the test. Ourgoal is to identify women who have true cervicalcancer precursor lesions (CIN 3, and to a lesserdegree CIN 2). The most common age for theselesions to be identified is in the 20s. Therefore, weshould focus our most active screening on those years.Almost all agencies now suggest annual screening toage 30. By that time most transient HPV infectionshave cleared, and those who are still cytology positivehave a greater likelihood of harboring a true cancerprecursor.10,11All preinvasive neoplasia of the cervix may regress. Although many different numbers can be foundin the literature, approximately 70 % of CIN 1, 50%of CIN 2, and 30% of CIN 3 (including those lesionscalled carcinoma in situ) disappear without treatment.12 Nonetheless,, treatment of HSIL is recommended for most women. Therefore, it seems reasonable to test women for the first time within 3 years ofcoitarche and to test yearly until age 30 years. If HSILOBSTETRICS & GYNECOLOGY
has not occurred by that time, it is unlikely that thewoman is at risk for significant cervical neoplasia andcan be tested less often.After age 30 I believe that it makes sense to testonly every 3 years. Many authorities have concludedthat every 3-year testing in that age group is just aseffective as annual screening and leads to fewerfalse-positive results, less anxiety, and less cost. I alsoadd HPV-DNA testing to the screen (see below), andif both the cytology and the high-risk panel arenegative, strongly discourage further Pap testing for atleast 3 years. The data are quite clear that a womanwho is 30 years of age and has a simultaneousnegative cytology and high-risk HPV-DNA test is atlower risk of HSIL in the next 3 to 5 years than thewoman who has 3 consecutive negative Pap testsalone.3,13–15 A few women are not comfortable withless frequent testing, and for them I continue yearlyscreening, but annually raise the concept of stretchingout the interval. Also, if yearly testing is continued, Ido not add the HPV-DNA test.The new guidelines also address the issue of“When to stop” cytology screening. When cervicalneoplasia progresses, it does so very slowly. Fewlesions progress to cancer, and several decades followthe earliest changes. From a practical standpoint, if awoman has been screened regularly and has not hadHSIL by the time she reaches age 70, it is unlikely thatshe can live long enough to develop the disease.16 Onthe other hand, she does need counseling and bloodpressure testing on an annual basis.17–29 If the Pap testis the only reason she sees her health care physician,it seems reasonable to continue to test.For 1 group of women, all of the current guidelines strongly discourage cytology screening: womenwho have had a hysterectomy for nonneoplasticdisease. The data show that most abnormal Pap testsin these women are falsely positive, and lead tounnecessary evaluation and treatment (Fig. 2).21For years I performed annual vaginal cytologyafter a hysterectomy for benign disease. Quite anumber of these tests were positive, especially whenthe vaginal epithelium became atrophic. I’ve performed hundreds of colposcopic examinations andbiopsies in these women. Most of the biopsies werereported as vaginal intraepithelial lesions grade 1(VAIN 1) with only a very rare VAIN 2 or 3. I’veagonized many times over the best way to treat thesepatients, because none of our modalities are verygood.Now, I no longer perform Pap testing on any ofthese women unless they have a history of HSILbefore their hysterectomy or are immunocompromised. Why did I change? First, I finally consciouslyrecognized a fact that I had known for years: VaginalVOL. 106, NO. 2, AUGUST 2005Fig. 2. Colpophotograph of the vaginal vault of a 76-yearold woman who had a Pap test reported as “Low-gradechanges consistent with vaginal intraepithelial lesionsgrade 1.” Despite negative examination findings both before and after treatment with estrogen cream, she remainedvery fearful of vaginal cancer.Noller. Cervical Cytology Screening and Evaluation. ObstetGynecol 2005.cancer is exceedingly rare. Most of us think of carcinoma of the fallopian tube as a rare cancer; vaginalcancer is even less common, and occurs almostalways in women with a history of HSIL of the cervix.Second, it has become clear that when the vaginalepithelium loses estrogenic stimulation, a biopsy willalmost always be difficult for a pathologist to interpret, and often the report will be VAIN 1. Third, Icannot remember a single case of VAIN 3 in awoman without a history of HSIL. When I finally “putit all together,” it became clear that all I had accomplished by doing Pap testing in these women was tocause needless anxiety, discomfort, and the morbidityassociated with treatment. I now limit Pap testing aftera hysterectomy for benign reasons to those womenwho previously had HSIL. If the report is VAIN 3 Istill suggest treatment, but I strongly suspect that fewof them would ever develop vaginal cancer.HPV-DNA TESTINGIt has been known for some time that infection withcertain types of the HPV is nearly always a requirement for the development of invasive cancer of thecervix. Unfortunately, these types have been labeled“high risk.” That term scares physicians and patientsalike. The truth is that the type of HPV most highlyassociated with cervical cancer, type 16, is both themost common (prevalent) HPV in the United Statesand that in the vast majority of infections it disappearsspontaneously and never causes significant disease.Women with evidence of a persistent “high risk”NollerCervical Cytology Screening and Evaluation393
infection (present for more than 2 years) need to befollowed up closely, because they represent the groupthat may develop a CIN 2 or CIN 3 lesion.8In 2003 the Food and Drug Administration reported that it had determined that the “high risk”panel of the HPV-DNA test, Hybrid Capture 2, wassafe and effective for cervical neoplasia screening, butadded strict conditions to its use.22–24 The test isapproved only for women aged older than 30 years,only every third year, and only with a simultaneouslycollected Pap test, not alone. This was the secondindication for the use of the test, because it hadalready been found to be of use in the triage ofwomen with atypical squamous cells of undeterminedsignificance (ASC-US) cytology reports.EVALUATION AND MANAGEMENT OFWOMEN WITH MINIMALLY ABNORMALPAP TESTSThe Bethesda System for the reporting of cervicalcytology was necessary because many laboratorieshad developed their own wording for abnormal reports. Although many of us initially struggled with thenew terminology, the fact that almost every laboratory in the nation now uses the same words makesreferral much easier. Initially there was confusionabout the meaning of the new terms, and many of usrelied on “expert” opinion for patient management.25INITIAL EVALUATION OF ABNORMALCERVICAL CYTOLOGY REPORTSSquamous AbnormalitiesASC-US B Three equally acceptablechoices:HR HPV-DNA testing(preferred)Repeat cytology in 6monthsColposcopyASC-H B ColposcopyLSIL B ColposcopyHSIL B ColposcopyCancer B ColposcopyGlandular Abnormalities*AGC-(any modifier) B ColposcopyAIS B ColposcopyAC B ColposcopyASC-US, atypical squamous cells of undetermined significance; HRHPV DNA, high-risk type of human papillomavirus DNA; ASC-H,atypical squamous cells, cannot rule out a high-grade lesion; LSIL,low-grade intraepithelial lesion; HSIL, high-grade intraepitheliallesion; AGC-US, atypical glandular cells of undetermined significance; AIS, adenocarcinoma in situ; AC, adenocarcinoma.* Additional tests may be needed based on patient age and history.394NollerCervical Cytology Screening and EvaluationA sufficient amount of time has now passed sothat we have “pretty good” data about the meaning ofthe Bethesda System results. When that is coupledwith what we have learned about HPV in the lastdecade, it is possible to design a clinically useful planfor the evaluation of every abnormal report.ASCCP convened a consensus conference inconjunction with the American College of Obstetricians and Gynecologists, the National Cancer Institute, and others and has published the results.26 Theanswer to most questions about the best plan for theevaluation of an abnormal cytology report can befound in the article. Unfortunately, it was written by acommittee and is very long. I will try to hit the highpoints, but if your specific patient does not fit into oneof the categories, you should consult the originalarticle.The good news is that it is relatively easy to knowwhat to do with most abnormal results. A summary ofthe most appropriate action for any report that isother than normal is presented in the box. It turns outthat the only result for which a decision about the firststep in evaluation needs to be made is for ASC-USreports. Because this is the most common abnormalresult, it is important to have a plan for these cases.The literature has documented that someASC-US reports are associated with HSIL.27 Therefore, some type of follow-up is needed. Fortunately,the National Cancer Institute funded a randomizedclinical trial with the purpose of determining the bestway to handle these cases. It turns out that any of the3 options shown in the box is effective.28 –29 Testing forhigh-risk types of HPV with HPV-DNA testing wasthe best by a slight margin. I believe that high-riskHPV-DNA testing is the best choice because it can beaccomplished with the most ease for both the patientand the physician. The secret is to use a liquid-basedtechnique and to ask your laboratory to performhigh-risk HPV-DNA testing automatically for anyASC-US report. This so-called “reflex testing” savesthe patient the time, effort and discomfort of anadditional examination, and the clinician the need toarrange follow-up for all ASC-US reports. It is important to be certain that your laboratory uses only thehigh-risk probe set. The low-risk panel has no clinicalusefulness and only adds needless expense. Considerchanging laboratories if yours insists on using thelow-risk probe.Because the most common HPV type in theUnited States is HPV 16, up to 60% of women whohave reflex testing will be high-risk positive and willneed colposcopy. However, the other 40% require nofurther testing for 1 year. That is, they should not berescreened for 12 months.I see quite a large number of young women in myOBSTETRICS & GYNECOLOGY
referral practice who have had abnormal cytologyreports and received treatment. Typically, they became sexually active and saw a physician for effectivecontraception. At the time of their visit they had a Paptest taken, and it was reported as either LSIL orASC-US. By the time I see these patients they havehad colposcopy, biopsy, and some form of treatmentfor LSIL, but remain cytology positive. On examination, many have some degree of cervical stenosis, andoccasionally it is severe. There is virtually never anysign of HSIL, and I routinely recommend cytologyfollow-up only. I worry how many of these womenwill have difficulty achieving pregnancy. For thesewomen who had a physician who overreacted to aminimally abnormal Pap test report, it would havebeen much better not to have had the test in the firstplace.One of the interesting facts in the history ofcytology screening is that cytologists acquired theability to identify women with a few minimally abnormal cells long before we knew what such cellsmeant. Since Pap testing was a cancer preventionstrategy, clinicians began to treat more and morewomen for less and less serious disease.30We now have a much better understanding of thenatural history of cervical neoplasia. The most important fact is that what is called “mild dysplasia” or“CIN 1” is virtually always a transient infection withthe human papillomavirus (HPV), and not a cancerprecursor.31 While a tiny minority of CIN 1 lesionscan progress, the light microscope cannot predictwhich lesions will disappear and which will not.The good news is that it is not very important toknow which lesions will go away and which ones willpersist. The important thing to realize is that there aremany years between CIN 1 and cancer, and thatnothing is lost by waiting, as long as the patient istreated if the lesion becomes CIN
lines for the use of Pap test screening, the evaluation of abnormal results, and management of low-grade cervi-cal neoplasia.3–5 In this article, I will explain how I have incorpo-rated some of the new guidelines into my practice, how the use of the human papillomavirus DNA (HPV-DNA) test can help us manage patients, and
– and prevents over 7 in 10 diagnoses. However, like any screening test, cervical screening is not perfect and there are some risks. Benefits of cervical screening Cervical screening aims to identify whether you are at higher risk of developing cervical cell changes or cervical cancer. This mean
3 ThinPrep LBC cervical cytology sample collection and preparation 9 4 Request forms Electronic requesting 10 5 Sending the sample to the laboratory 12 6 Reporting cervical screening results 12 7 Patient management protocols 7.1 Independent sector cervical screening samples 7.2 Inappropriate & Out of Programme [ samples
Conclusions: The study revealed utilization of cervical cancer screening service was low among HIV positive women. Educational status, duration of HIV diagnosis, partner support, knowledge status about risk factor, CD4 count and attitude towards cervical cancer and its screening were associated with cervical cancer screening utilization.
What is Liquid Based Cytology? Liquid Based Cytology (LBC) is a method of preparing cytological specimens by suspending the samples in a preservative collection fluid immediately after collection. It is also possible to process fresh, unpreserved samples received in the Cytology laboratory by following the Liquid-Based Cytology procedure.
screening may stop for those women without history of CIN2 or higher grade lesion, even if there is no history of adequate screening. Again, screening should not resume for any reason. For those women with a history of CIN, AIS or cancer, Pap smear screening via cervical cytology only should continue for 25 years regardless of whether the cervix is
woman or the Cervical Cytology Form. In order to be accepted at the laboratory, a slide or vial must contain at a minimum: the woman's surname, first name / initial and date of birth. These details must all exactly match the details on the Cervical Cytology Form. Figure 4.5 Preparing sample for laboratory Submitting samples to the laboratory
One Device for Sample Collection in All Patients. Cervical Cancer Screening Devices for Liquid Based Cytology . and Conventional Specimen Collection from Rovers Cytology/Histology. Contact Therapak for free samples of all specimen collection devices. Part No. Description Packed 36827 Rovers Cervex-Brush Combi 25/pack, 500/case
CERVICAL SCREENING NEWSLETTER July 2018 The purpose of this newsletter is to provide information and updates in relation to staff involved in the National Cervical Screening programme across Kent and Medway. In This Issue: High -Risk HPV Primary Testing Result Letters Extended H ours? Contacting N on -R esponders :
