Colposcopy with possible biopsy. H-SIL (High-grade squamous intraepithelial lesion)*: includes changes suggestive of CIN2 and CIN3/CIS. The cytologic diagnosis must be confirmed by biopsy, for which it is necessary to perform a directed biopsy by colposcopy.

A 45-year-old woman, mother of 3 children, attends an early diagnosis consultation. Cervicovaginal cytology is compatible with a high-grade squamous intraepithelial lesion. Which of the following options would you choose?

Hysterectomy with bilateral salpinguectomy and ovarian conservation.

Gynecology_Novak

2. Treatment is recommended for a histologic diagnosis of CIN 3 or if colposcopy is unsatisfactory. Although invasive cervical cancer is very rare in this age group, prospective follow-up of a histological diagnosis of CIN 2 or 3, not otherwise specified, in young women should be limited to those women likely to be compliant with the recommendations. 3. After 2 consecutive negative for intraepithelial lesion or malignancy results, implying negative cytology and colposcopy with satisfactory colposcopic examinations, adolescents and young women can return to routine cytologic screening. An annual screening interval should be recommended. 4. Treatment is recommended if CIN 3 is diagnosed histologically or if CIN 2 or 3 persists for 24 months. 1. Hysterectomy remains the preferred management recommendation for women with a histological diagnosis of AIS on a specimen from a diagnostic excisional procedure (Fig 19.16F). 2.

Comparing two modalities of management of women with cytologic evidence of squamous or glandular atypia: early repeat cytology or colposcopy.

Early repeat cytology is recommended in most screening programs for cervical cancer in subjects with squamous or glandular abnormalities not amounting to neoplasia (atypical squamous cells of undetermined significance, ASCUS), but immediate colposcopy is also recommended in some countries, especially those where there is easy access to colposcopic facilities. We evaluated the cost-effectiveness of the two procedures in a prospective study of women with cytologic ASCUS, invited to cytocolposcopic assessment after 6 months. Colposcopy-directed biopsy was assumed as the gold standard, and the accuracy of colposcopy at 6 months was assumed to be equal to that of immediate colposcopy. Out of 874 compliers, punch biopsy was performed in 303 cases (34.7%), and 19 CIN2+ lesions were detected (CIN2 = 12, CIN3 = 6, microinvasive carcinoma = 1). Detecting 13 CIN2+ lesions at colposcopy required 874 colposcopies and 303 directed biopsies: the cost per CIN2+ lesion detected with the procedure was 2,749 US$. Detecting 15 CIN2+ lesions at repeat cytology required 874 cytologic examinations, 137 colposcopies, 64 directed biopsies, and 6 diagnostic large-loop resections, the latter being performed in subjects with high-grade squamous intraepithelial lesion and less severe lesions at punch biopsy: the cost per CIN2+ lesion detected with the procedure was 1,961 US$. The policy of repeat smear was more cost-effective than immediate colposcopy. According to such results, the protocol of the Florence screening program has been modified since October 1996.

Cervical Intraepithelial Neoplasia -- Treatment / Management

Women treated for CIN-2, or greater should have a Pap smear and HPV testing 12 and 24 months after the procedure. Even with positive endocervical margins on an excised specimen, the procedure is deemed 70 to 80% effective. When margins are positive, repeat cytology testing in 4-6 months accompanied by an endocervical curettage is the course of action.  A repeat excisional procedure is one option for treatment of persistent or recurrent CIN-2 or 3. In some circumstances, patients will opt for a hysterectomy, which is also appropriate for recurrent CIN. [1]

Gynecology_Novak

7. A repeat diagnostic excisional procedure is acceptable. The Guidelines allow for hysterectomy if a repeat diagnostic excisional procedure is not feasible. An undisclosed invasive cancer within the endocervical canal must be excluded prior to hysterectomy. 8. For women with histologically proven residual/recurrent CIN 2 or 3, the Guidelines permit a repeat excisional procedure or hysterectomy. 1. For adolescents with a histological diagnosis of CIN 2 or 3 not otherwise specified, the Guidelines state that either treatment or observation by cytology and colposcopy every 6 months for up to 24 months is acceptable provided colposcopy is satisfactory (Fig 19.16E). Allowing for the subjectivity in this histological distinction, observation is preferred for a diagnosis of CIN 2 alone, but treatment is acceptable. 2.

Surgery_Schwartz

1790SPECIFIC CONSIDERATIONSPART IIHPV test performed at the same time also is negative, test-ing should be repeated every 5 years for women ages 30 to 65 years. Screening is not recommended for women age older than 65 or without a cervix (prior hysterectomy) unless they have a history of high-grade precancerous lesions. Women with a history of cervical dysplasia, HPV infection, or cervical cancer need more frequent screening based on their diagnosis. Primary high-risk HPV (hrHPV) screening is also an acceptable alterna-tive to cytologic screening for women ages 30-65 because of an increased detection of high-grade squamous intraepithelial lesion (HSIL) and increased negative predictive value.6HPV Vaccine. Three HPV vaccines have been approved by the U.S. Food and Drug Administration (FDA).7 In 2006, a quad-rivalent (4vHPV) vaccine was approved that targets HPV 16 and 18, which cause 70% of cervical cancers, and HPV geno-types 6 and 11, which cause 90% of genital warts. In Decem-ber

Clinical evaluation of follow-up methods and results of atypical glandular cells of undetermined significance (AGUS) detected on cervicovaginal Pap smears.

The aim of this study was to evaluate the efficacy of the follow-up methods and results of atypical glandular cells of undetermined significance (AGUS) detected on cervicovaginal Pap smears. From May 1991 to December 1996, we have performed 407, 451 cervicovaginal Pap smears, of which 326 patients were identified as AGUS. Of the 326 patients, 268 patients were followed by repeat Pap smears, colposcopy, cone biopsy, or endometrial curettage. The incidence of AGUS on Pap smears is approximately 0.08%. The mean age of the patients was 43 years (range 22-79 years). The most common complaint was abnormal vaginal bleeding. The gross findings of the cervix were normal to mild erosion. The following past histories of patients could affect the AGUS results on Pap smear: 30 had cone biopsy, 21 had Pap smears on pregnancy and within 8 weeks after delivery or evacuation, 3 were on hormonal replacement therapy, 2 had intrauterine devices for contraception, and 5 were undergoing follow-up after treatment of cervical cancer. The benign lesions detected during follow-up periods were 6 microglandular hyperplasia of the cervix, 5 atypical squamous metaplasia of the cervix, 2 cervical endometriosis, 2 tubal metaplasia, 10 cervical myoma, 11 cervical polyps, 9 endometrial polyps, 3 uterine myoma, 1 pelvic endometriosis, 1 ovarian endometriosis, and 4 uterine adenomyosis. The premalignant or malignant lesions of the cervix were 4 low-grade squamous intraepithelial lesions, 24 high-grade squamous intraepithelial lesions, 8 glandular atypia/dysplasia, 5 adenocarcinoma in situ, 3 microinvasive adenocarcinoma, and 4 invasive adenocarcinoma. The neoplastic lesions of the uterus were 6 endometrial hyperplasia, 11 endometrial adenocarcinoma, 1 malignant mixed Müllerian tumor, and 1 metastatic endometrial adenocarcinoma. Sixty-seven (25%) of 268 patients followed up were identified as having clinically significant lesions of the cervix or uterus. The detection rates of abnormal lesions were 3.1% with repeated Pap smears (3/98), 28.4% with colposcopic-directed biopsy (31/109), 63.6% with cone biopsy (35/55), and 29.7% with endometrial curettage (19/64). AGUS on Pap smears showed various benign and malignant lesions of the cervix or uterus. The clinicians must communicate with the pathologists regarding the patient's clinical information as well as the origin of the atypical glandular cells in Pap smears. We recommend that patients with AGUS on Pap smear should undergo immediate intensive diagnostic studies, including colposcopic-directed biopsy with endocervical curettage or cone biopsy, to detect cervical lesions and endometrial curettage to detect endometrial lesions.

Recurrent smear abnormalities where repeat loop treatment is not possible: is hysterectomy the answer?

The objective of this study was to determine the outcome of women who underwent hysterectomy for recurrent cytological abnormalities where repeat loop treatment was considered not to be technically possible because of insufficient remaining cervical tissue. Women undergoing a hysterectomy for the above indication at the Northern Gynaecological Cancer Centre over a period of 10 years (1992-2001) were identified from a prospectively collected database. Case notes were then reviewed and women undergoing hysterectomy for other indications were excluded. Relevant demographic and clinical data were then extracted. 33 patients meeting the above criteria were identified. The overall hysterectomy rate for this indication was 0.73%. 20 out of the 33 women had significant pathology on the hysterectomy specimen. 95% of these had high-grade disease with one having a Stage 1A1 squamous carcinoma. None of the patients required more radical treatment than a simple hysterectomy. There were no major complications following the hysterectomy. Positive endocervical margins on the previous loop specimen (P = 0.05) was an important correlating factor predicting the presence of CIN on the hysterectomy specimen. One out of the thirty hysterectomies (3.3%) performed using the vaginal route had incomplete excision compared to one of three (33%) using the abdominal route. Hysterectomy was successful in treating 85.2% of the women; only 4 women subsequently developed vaginal intraepithelial neoplasia. Simple hysterectomy appears to be a suitable diagnostic and treatment option for women with recurrent high-grade cytological abnormalities where further loop treatment is technically not possible. Incomplete excision at the endocervical margin on the previous loop specimen was the main factor associated with the presence of cervical intraepithelial neoplasia at hysterectomy.

[Management of CIN1].

A cervical intraepithelial neoplasia grade 1 (CIN1) is a lesion of basal cells consisting in an architecture disorganization and cytological atypia limited to the lower third of the cervical epithelium. It is considered as a precancerous lesion uterine cervix carcinoma while they spontaneously regress in more than 60% of cases in two years. The problems related to the management of CIN1 as defined by the recommendations established in 2002 are the over-treatment and the great variability of clinical practices. Moreover, the potential of new tests has been investigated since 2002. To establish these new recommendations, the medline database has been consulted and the references essentially published between 2001 and May 2007 have been investigated. Publications were selected and classified according to their level of evidence (LE) in order to establish the grade of recommendations. One of the problems encountered when facing a CIN1 is to misdiagnose a more severe lesion firstly because of the intra- and interobserver variability and secondly because the colposcopy-directed biopsy is not mandatorily representative of the more severe lesion. Nevertheless, because the risk of cancer is extremely low, a conization is not necessary in an asymptomatic woman with a LSIL/ASC-US pap smear in case of CIN1 even if the squamocolumnar junction is not entirely visualized (LE 2/3). The endocervical curettage cannot be recommended in this case because its efficacy is globally poor and unknown in case of CIN1. Concerning the natural history of CIN1, the recent studies, which included more than 1200 women and more than 700 for two of them, confirm that the rate of progression of a CIN1 to a CIN3 or more severe lesion is less than 9% in the two years following the initial diagnosis (LE2). A CIN1 is associated with a risk of evolution to a CIN2 or more severe lesion that is not markedly more important than the risk associated with a LSIL/ASC-US pap smear while the colposcopy is normal or the biopsy is negative (between 8 and 13% whatever the results of the initial colposcopy) (LE 2/3). The recommendation in case of CIN1 is a strict follow-up. A colposcopy and a treatment are necessary in case of persistence or progression of the abnormalities (LE2). Data from trials studying the contribution of HPV testing in case of CIN1 show that its sensitivity is similar to repeat cytology with less referral to colposcopy to detect CIN2 or more severe lesion. These data have been considered to establish follow-up recommendations to manage CIN1: if the exams (cytology and/or HPV testing) at 12 months are negative, patients can be followed by an annual cytology. In case of aggravation of the cytology, a colposcopy is necessary. In case of positive HPV testing or persisting ASC-US/LSIL at 12 months, a repeat control is necessary at 18 months and a treatment is proposed according to colposcopy findings.

[Review of cervical smears in a gynaecologic department after a period of ten years under the consideration of colposcopic findings(author's transl)].

The study comprises 96042 cytologic cases within a period of 10 years. After screening women were admitted for biopsies. The histologic findings are reported. By 690 "right positive smears" 71 squamous cell cervical cancers stage Ib or more 87 microcarcinomata-1, 377 carcinomata-in-situ of the cervix, 100 dysplasias, 47 adenocarcinomata and 8 different malign tumors were found. 61 cases having histologic diagnosis outside are just mentioned. 629 cases which had been diagnosed in our hospital are described extensively. The first biopsy was nearly always taken by selective scraping of the ecto- and endocervix. Technical improvements of this method are explained. The efficiency of cytodiagnosis is especially pointed out by separating cases which could have been recognized or suspected by means of inspection or colposcopy only. 140 out of 282 carcinomata-in-situ and 7 invasive, mainly endocervical cancers (Ib-III), could only be diagnosed by a smear. In 17 woemn who turned out to have invasive cancer (Ib -III) a positive smear was the only reason for admission. Careful inspection of the cervix in the hospital, however, was sufficent to reveal the correct diagnosis. In our material the cervical smear could be of little help in cancer diagnosis of the upper genital tract such as adenocarcinoma of the corpus uteri, sarcoma and ovarian cancer. 39 of the 45 women with endometrial cancer cells in the specimen had bleeding anomalies, especially postmenopausal. The number of "false negative smears" mainly yields from histologic examination of 2415 uteri after hysterectomy and 4497 specimen after curettage of cervix and corpus uteri. In the first group 1 microcarcinoma-2 and 5 carcinomata-in-situ, in the second group which obviously is less representative 4 carcinomata-in-situ were found unexpectedly. It is also searched for cases which had a negative smear first and a positive or suspect smear later. This happened in 41 patients. The underlying lesion were 5 advanced cancers, 2 microcarcinomata-3 and 34 carcinomata-in-situ. Up to 30 months elapsed between the last negative cytologic finding and histologic diagnosis. 121 out of 811 suspect or positive smears were "false positive". Cytologic grouping III, IV and V inconsistently matched with the corresponding histologic results. The type and extension of squamous cell atypias are anticipated with little certainty. The great number of suspect specimen (group III) both in microcarcinoma-4 (6 in 78) and carcinoma-in-situ (33 in 344) was striking. Therefore we consider a histologic diagnosis to be necessary in this group as well as in group IV and V. The method of fractioned cervical scraping makes the decision of hospital admission easier. Low risk for the patient does not imply any loss in diagnostic security.

Diagnosis of Cervical Precancers by Endocervical Curettage at Colposcopy of Women With Abnormal Cervical Cytology.

To evaluate the performance of routine endocervical curettage (ECC) for diagnosing high-grade cervical intraepithelial neoplasia (CIN) 2 or worse and additional precancers not otherwise detected by ectocervical biopsies. In a secondary analysis of the Biopsy Study, a cross-sectional study conducted between 2009 and 2012 at the University of Oklahoma Health and Sciences Center that found an incremental increase in detection of cervical precancers by multiple biopsies at colposcopy, ECC was performed in most women aged 30 years or older. Cervical intraepithelial neoplasia 2 or worse yield by ECC alone was evaluated in analyses stratified by cervical cytology (atypical squamous cells of undetermined significance [ASC-US] or low-grade squamous intraepithelial lesions [LSIL] compared with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesions [ASC-H] or high-grade squamous intraepithelial lesions [HSIL] or worse), colposcopic impression (less than high-grade compared with high-grade), human papillomavirus (HPV)-16 infection status, whether the examination was satisfactory, and by ECC indications per the current guidelines for cervical cancer screening. The diagnostic value of ECC for detecting additional disease was evaluated by the number of lesion-directed ectocervical biopsies. Of the 204 women aged 30 years or older, 181 (88.7%) underwent ECC. Overall ECC detected 14.4% CIN 2 or worse (95% CI 10.0-20.2%). Endocervical curettage was more likely to find disease in the endocervix among women with high-grade cytology, positive HPV-16 infection, or high-grade colposcopic impressions (respective P values <.05). Among women with ASC-US or LSIL cytology, those with an unsatisfactory examination had a 13.0% CIN 2 or worse yield on ECC (95% CI 6.1-25.7); when colposcopic examination was normal or satisfactory with visible abnormal lesions, ECC detected less than 5% CIN 2 or worse in the endocervix. An ASC-H or HSIL or worse cytology was associated with a CIN 2 or worse yield of 25.8% by ECC (95% CI 16.6-37.9%). However, ECC found only 3.9% (95% CI 1.9-7.8%) additional CIN 2 or worse beyond the cumulative disease detected by up to four biopsies of visible acetowhite ectocervical lesions. Additional CIN 2 or worse yield by ECC increased when fewer lesion-directed biopsies were taken (P<.05). The additional yield of CIN 2 or worse by ECC in a colposcopy with up to four ectocervical biopsies was low. Based on our findings, we recommend routine ECC be performed in women aged 45 years old or older with HPV-16 infection and in any woman aged 30 years or older with HSIL or worse or ASC-H cytology, high-grade colposcopic impression, or ASC-US or LSIL cytology and an unsatisfactory examination. ClinicalTrials.gov, NCT00339989.

See and treat strategy by LEEP conization in patients with abnormal cervical cytology.

To determine the overtreatment and re-LEEP rates of see and treat strategy (S & T) in women who underwent S & T by LEEP and to identify the risk factors for overtreatment and surgical margin and/or endocervical curettage positivity. A total of 800 patients who underwent S & T in Istanbul University Cerrahpasa Medical Faculty between June 2010 and June 2016 were retrospectively analyzed. Overtreatment rate was found to be 46.6%, decreasing with higher grade of cervical smear abnormalities. Age more than 45, low grade of cervical cytologic abnormality and absence of glandular involvement were associated with higher overtreatment rates. The more advanced the histopathology, the more increased risk of surgical margin on LEEP and ECC positivity (p < 0.0001, for both). Glandular involvement was associated with both surgical margin and ECC positivity. S & T can be used in patients with high grade cytologic anomaly with an acceptable overtreatment rate. In addition, bigger pieces of specimens may need to be removed during LEEP in patients who have suspicious images of higher grade of abnormalities on colposcopy to reduce surgical margin or ECC positivity. When high rate of ECC positivity in patients with HSIL cytology is considered, we suggest performing ECC to every patients with HSIL.

Bethesda system

CIN 1 is the most common and most benign form of cervical intraepithelial neoplasia and usually resolves spontaneously within two years. Because of this, LSIL results can be managed with a simple "watch and wait" philosophy. However, because there is a 12–16% chance of progression to more severe dysplasia, the physician may want to follow the results more aggressively by performing a colposcopy with biopsy. If the dysplasia progresses, treatment may be necessary. Treatment involves removal of the affected tissue, which can be accomplished by LEEP, cryosurgery, cone biopsy, or laser ablation. HSIL: high-grade squamous intraepithelial lesion High-grade squamous intraepithelial lesion (HSIL or HGSIL) indicates moderate or severe cervical intraepithelial neoplasia or carcinoma in situ. It is usually diagnosed following a Pap test. In some cases these lesions can lead to invasive cervical cancer, if not followed appropriately.

Human papillomavirus testing as triage for atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions: sensitivity, specificity, and cost-effectiveness.

Our purpose was to evaluate the cost-effectiveness of the use of a Food and Drug Administration-approved human papillomavirus test in triaging patients with Papanicolaou smears showing atypical squamous cells of undetermined significance or a low-grade squamous intraepithelial lesion for colposcopy compared with an algorithm that used cytologic follow-up. Four hundred sixty-two women referred to our Colposcopy Clinic with a Papanicolaou smear report of atypical squamous cells of undetermined significance or a low-grade squamous intraepithelial lesion underwent repeat Papanicolaou smear, cervical colposcopy, directed cervical biopsy, and endocervical curettage. In addition, human papillomavirus testing by the Food and Drug Administration-approved HPV Profile (Digene Diagnostics, Silver Spring, Md.) test was done. A comparison of sensitivity, specificity, and cost-effectiveness of an algorithm determining the need for colposcopy on the basis of repeat cytologic testing versus an algorithm that incorporated repeat cytologic testing and human papillomavirus screening was done. The cost-effectiveness of both of these triage algorithms was also compared. As expected, high-risk human papillomavirus deoxyribonucleic acid was detected with greater frequency in relation to increasing severity of cervical intraepithelial neoplasia. In 268 women, the follow-up smear obtained in our clinic was reported as negative. High-risk human papillomavirus types were found in 23.5% of these women. In the human papillomavirus-negative women, 5.9% had grade 2 or 3 cervical intraepithelial neoplasia confirmed on cervical biopsy. In comparison, 20.6% of those with a positive result of the human papillomavirus test had grade 2 or 3 cervical intraepithelial neoplasia on biopsy (p < 0.001). Despite this difference, the sensitivity of a positive result of a high-risk human papillomavirus test in predicting the presence of grade 2 or 3 cervical intraepithelial neoplasia was only 52%. Among the women for whom a follow-up clinic Papanicolaou smear was reported as showing atypical squamous cells of undetermined significance or a low-grade squamous intraepithelial lesion, there was no difference in the frequency of biopsy-proved grade 2 or 3 cervical intraepithelial neoplasia between those women with a positive human papillomavirus test result and those with a negative test result. Colposcopy would have been recommended for 194 women because of a repeat clinic smear revealing atypical squamous cells of undetermined significance, a low-grade squamous intraepithelial lesion, or a high-grade squamous intraepithelial lesion, and in 21.6% of these grade 2 or 3 cervical intraepithelial neoplasia was shown on biopsy (sensitivity 63%, specificity 62%). Colposcopy would have been recommended for 180 women because high-risk human papillomavirus or a high-grade squamous intraepithelial lesion was detected at the clinic visit, and in 25% of this group grade 2 or 3 cervical intraepithelial neoplasia was shown on biopsy (sensitivity 67%, specificity 66%). Sensitivity and specificity were virtually identical for the two algorithms, but the cost of human papillomavirus testing was nearly double that of triage based on repeat cytologic testing alone ($692 vs $1246 per case). The Food and Drug Administration-approved HPV Profile test is not a cost-effective triage for patients referred with Papanicolaou smears reported as showing atypical squamous cells of undetermined significance or low-grade squamous lesions.

Abnormal Pap smears: a comparison of total abdominal hysterectomy and cone biopsy in management.

A recent study found that colposcopy is still not available to over 50% of gynaecologists practicing in Nigeria and that 91% of them will do either cone biopsy or hysterectomy for moderately or severely abnormal Pap smears. Currently, there are no local data to guide such patient care. In order to compare cone biopsy and hysterectomy in terms of their pick-up rates of cervical intraepithelial neoplasia and invasive cancer in women with abnormal pap smears, a retrospective review of entries in the histology reports of all cases of cone biopsy and hysterectomy done for abnormal Pap smears from 1975-2004 at the histopathology department of the University of Nigeria Teaching Hospital, Enugu, Nigeria, was carried out. The study revealed that 203 women with moderately to severely abnormal Pap smears were treated with either cone biopsy or hysterectomy. A total of 88 (43.3%) women had cone biopsy, while the remaining 115 (56.7%) had total abdominal hysterectomy. Those who had cone biopsy were significantly younger than those who had hysterectomy (mean ages: 44.6+/-8.8 vs 52.3+/-9.8 years; p=0.008). There was no significant difference in parity between those who had cone biopsy and those who had hysterectomy (mean parity: 5.7+/-2.3 vs 6.5+/-2.2; p=0.102). For all the 203 women, the histology was reported as normal in 97 (47.8%) women and inflammatory in six (3.0%). The three cases of invasive cervical carcinoma were found in women with moderately abnormal Pap smears. One had a cone biopsy, while the other two had a simple total abdominal hysterectomy. Cone biopsy and hysterectomy did not differ significantly in their pick-up rates of the various categories of cervical lesions including invasive carcinoma (p>0.05 for all categories). It was concluded that cone biopsy and hysterectomy have similar pick up rates for the various types of cervical lesions. For this reason, in the absence of colposcopy as occurs in many parts of the developing world, cone biopsy may be adequate treatment and should be offered first to women with moderately to severely abnormal Pap smears.

Pitfalls in the diagnosis of cervical intraepithelial neoplasia 1.

This review article outlines the issues involved in (1) the cytologic diagnosis of low-grade squamous intra-epithelial lesion (cervical intraepithelial neoplasia [CIN] 1), (2) histologic diagnosis of CIN 1, (3) the advantages and disadvantages of various management strategies for CIN 1 confirmed by biopsy, and (4) the evolving technology that may be useful for predicting the course of the disease. A MEDLINE search was conducted using the search terms cervical intraepithelial neoplasia, low-grade dysplasia, mild dysplasia, low-risk squamous intraepithelial lesion, mild dyskaryosis, HPV, colposcopy, histology, and cytology. RESULTS.: Using a loop electrosurgical excision procedure or cone biopsy assessment of the cervix as the gold standard, a cytologic assessment of CIN 1 alone results in a high false-positive rate (51.5%) and a false-negative rate (24%) for CIN 3. The appropriate second test after low-grade squamous intraepithelial lesion (CIN 1) cytologic results includes repeat cervical cytologic analysis. Subsequent human papillomavirus testing provides no advantage and increases the cost of care. Immediate referral to colposcopy is costly but minimizes the percent of women lost to follow-up. Using a loop electrosurgical excision procedure or cone biopsy assessment of the cervix as the gold standard, the colposcopically directed biopsy may give a false-positive result (11.7%) or false-negative result (up to 31%) for CIN 3. One contributing issue is the moderate interobserver reliability of histologic analysis (kappa= 0.46). There are advantages and disadvantages to both the immediate and expectant management strategies. The most crucial concern for immediate treatment is overtreatment, and that for expectant management the high rate of patients lost to follow-up. Novel technologies, including MIB-1, p16(INK)4a, and genetic assessments, may be helpful in predicting those CIN 1 lesions destined to progress or to persist. The cytologic and histologic diagnosis of CIN 1 is fraught with problems related to the subjectivity of the diagnosis. Both management options are also fraught with concerns. Any technique that can better predict disease course would be an advantage to the care of women with this abnormality.

A prospective evaluation of "see and treat" in women with HSIL Pap smear results: is this an appropriate strategy?

The evaluation of abnormal cervical cytologic results is time consuming and costly. Most patients with high-grade squamous intraepithelial lesion (HSIL)-cervical intraepithelial neoplasia 3 (CIN 3) Pap smear results require an excisional procedure for diagnostic or therapeutic reasons. "See and treat" is a surgical procedure that involves a loop electrosurgical excisional procedure (LEEP) simultaneously to diagnose and to treat premalignant cervical disease in one visit. This procedure eliminates a second visit that typically is required for treatment. Data is lacking on the incidence of CIN 2 and CIN 3 in patients with an HSIL (CIN 2) Pap smear result. The objective of this study was to determine the incidence of CIN 2 and CIN 3 in patients with an HSIL (CIN 2) Pap smear using a see-and-treat protocol. Women referred from local health departments to our university-based colposcopy clinic for evaluation of an HSIL (CIN 2) Pap smear result were evaluated for inclusion in a see and treat protocol. All eligible patients underwent colposcopy to rule out an obvious cervical carcinoma followed by an immediate LEEP to remove the transformation zone. A colposcopic impression was made using the Reid colposcopic index. Pathologic specimens were analyzed for the presence of CIN and the incidence of CIN 2 and CIN 3 was determined. To date, 51 patients have been enrolled in the study. Exclusion criteria included age less than 19 years, pregnancy, or medical contraindications. The mean age of the patients was 26 years (range, 19-45 years). Forty-seven percent were white, 47% were black, and 6% were Hispanic. Of the 51 patients who underwent LEEP, 43 of 51 (85%) had satisfactory colposcopy and no patient had a lesion suspicious for cervical carcinoma. The average Reid colposcopic index was 3.5. Of the 51 LEEP specimens, 4 of 51 had no evidence of CIN (8%), 4 of 51 (8%) had CIN 1, 18 of 51 (35%) had CIN 2, and 25 of 51 (49%) had CIN 3. Eighty-four percent of patients had either CIN 2 or CIN 3, resulting in an overtreatment rate (CIN 1 or less) of 16%. The use of a see and treat protocol for patients with HSIL (CIN 2) Pap smear results may be an acceptable treatment option because of a high incidence of CIN 2 and CIN 3.

Follow-up of women with cervical cytological abnormalities showing atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion: a nationwide cohort study.

Atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion in abnormal cervical cytology among young women in cervical cancer screening is an increasing health burden, and comparative effectiveness studies of different management options for such diagnoses are needed. The objective of the study was to compare the incidence of invasive cervical cancer, following different management options pursued after an atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion index smear. In this nationwide cohort study, we included all women aged 22-50 years and resident in Sweden 1989-2011 and with at least 1 cervical smear registered during the study period (n = 2,466,671). Follow-up of a first atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion cytological diagnosis within 25 months was classified as repeat cytology, colposcopy/biopsy, or without further assessment. Incidence rate ratios and 95% confidence intervals of subsequent cervical cancer within 6.5 years following atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion were estimated using Poisson regression by age group and management strategy. Women managed with repeat cytology within 6 months after atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion cytology had a similar risk of cervical cancer compared with colposcopy/biopsy (incidence rate ratio, 1.1, 95% confidence interval, 0.5-2.5, and incidence rate ratio, 2.0, 95% confidence interval, 0.6-6.5, respectively) among women aged 22-27 years. For women aged 28 years and older, women managed with repeat cytology had a higher risk for cervical cancer than women managed with colposcopy/biopsy. Our findings suggest that women with a first cytological diagnosis of atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion up to age 27 years may indeed be safely followed up with repeat cytology within 6 months. A large amount of colposcopies that are currently performed in this group, therefore, could safely be discontinued.

[Is it necessary to make screening pap smears after hysterectomy?].

To precise the risk of cancer of the vagina after hysterectomy. In our file of cervicovaginal and vulvar pathology, we looked for all VAIN and invasive cancers of the vagina on a 10-year period. Out of 2152 patients, we found but 45 cases, 13 of which only after total or radical hysterectomy: 4 cases of invasive cancer of the vagina (1 after radical hysterectomy for invasive cancer of the cervix, and 3 after total hysterectomy for CIN); 9 cases of VAIN (5 after total hysterectomy for CIN; and 4 VAIN (3 after radical hysterectomy for cervical invasion). In our series, we did not observe precancerous or invasive lesion of the vagina after hysterectomy for benign lesion. Indeed, the 13 cases of invasive or in situ cancers of the vagina we found had undergone simple or radical hysterectomy for cervical lesion. We think that the cytological follow-up of the vaginal vault after hysterectomy for benign lesion can be, if not stopped, at least quite spaced out. On the other hand, the follow-up must be imperatively maintained in the event of hysterectomy for precancerous lesion or cancer of cervix.

A randomized trial on the management of low-grade squamous intraepithelial lesion cytology interpretations.

This study was undertaken to compare alternative strategies for the initial management of low-grade squamous intraepithelial lesion (LSIL) cytology. A total of 1572 women with a community-based LSIL interpretation were randomly assigned to immediate colposcopy, triage based on enrollment HPV DNA testing and liquid-based cytology at a colposcopy referral threshold of high-grade squamous intraepithelial lesion (HSIL), or conservative management based on repeat cytology at a referral threshold of HSIL. All arms included 2 years of semiannual follow-up and colposcopy at exit. Loop electrosurgical excision procedure was offered to women with histologic diagnoses of cervical intraepithelial neoplasia (CIN) grade 2 or 3 at any visit or persistent CIN grade 1 at exit. The main study end point was 2-year cumulative diagnosis of CIN grade 3. The 2-year cumulative diagnosis of CIN grade 3 was approximately 15% in all study arms. The HPV triage arm was closed early because more than 80% of women were HPV positive, precluding efficient triage. The immediate colposcopy strategy yielded 55.9% sensitivity for cumulative cases of CIN grade 3 diagnosed over 2 years. A conservative management strategy of repeat cytology at the HSIL threshold referred 18.8% of women while detecting 48.4% of cumulative CIN grade 3. At lower cytology thresholds, sensitivity would improve but would ultimately yield unacceptably high referral rates. LSIL cytology is best managed by colposcopy initially, because there was no useful triage strategy identified. Management of these patients, after colposcopy to rule out immediately overt CIN grade 2 or 3, needs to be determined.

Role of vault cytology in follow-up of hysterectomized women: results and inferences from a low resource setting.

The study was undertaken to assess the utility of cervico-vaginal/vault cytology in the follow-up of women treated for cervical cancer and benign gynecological conditions. Records of 3,523 cervico-vaginal smears from 2,658 women who underwent hysterectomy and/or radiotherapy or chemotherapy, over a 10-year period were retrieved. Data was collected on type of treatment received, indication for hysterectomy, age of patient, presenting symptoms, stage of tumor, interval since treatment, cytology and biopsy results. The results of cytology versus other parameters were analyzed separately for women treated for cervical cancer and those hysterectomized for benign indications. Malignant cells were detected in 141/1949 (7.2%) follow-up smears from treated cervical cancer cases (140 recurrences and 1 VAIN). Around 92% of recurrences of cervical cancer were detected with in 2 years of follow-up and 75% of these women were symptomatic. Cytology first alerted the clinicians to a recurrence in a quarter of cases. On the other hand, VAIN was detected in 5/1079 (0.46%) vault smears from 997 women hysterectomized for benign gynecologic disease. All these women were asymptomatic and majority (80%) were detected in follow-up smears performed between 3 and 10 years. Vault cytology is an accurate tool to detect local recurrences/VAIN in women treated for cervical cancer or benign gynecological conditions. It may even first alert the clinicians to a possibility of recurrence. However, due to extremely low prevalence of VAIN/vaginal cancer, it seems unwarranted in women hysterectomized for benign indications, especially in resource constrained settings.

Adenoid basal carcinoma of the cervix: a potential pitfall in cervicovaginal cytology.

Adenoid basal carcinoma (ABC) of the cervix is a quite uncommon, indolent, yet invasive neoplasm rarely identified on cervicovaginal smears. This may be due in part to sampling. Unless ABCs become ulcerated, even vigorous brushing of the endocervical canal may not be adequate to dislodge the small, cohesive cells of this neoplasm. Fortunately, the association of ABC with squamous intraepithelial lesions (SIL) often results in its incidental diagnosis on follow-up cervical biopsy or endocervical curettage. We report two cases of ABC. In case 1, a 79-yr-old white woman was diagnosed with squamous-cell carcinoma on cervicovaginal (CV) smear. High-grade SIL, carcinoma in situ, and ABC were identified on subsequent cervical cone biopsy and hysterectomy. Retrospective evaluation of the CV smear revealed a few aggregates of small, uniform cells, with hyperchromatic nuclei representing fragments of ABC. In case 2, atypical basaloid cells suspicious for ABC were recognized on the CV smear of a 67-yr-old black woman, and ABC was subsequently confirmed on cervical cone biopsy. In neither case did the intervening cervical biopsy reveal ABC. In addition to a review of the clinical information useful in the diagnosis of ABC, the cytologic features of these two cases are compared with their subsequent histopathology and contrasted with other similar lesions comprising the differential diagnosis of small neoplastic cells found in cervicovaginal smears.

Post-Conization FIGO stage IA1 squamous cell cervical carcinoma; is hysterectomy necessary?

To compare and evaluate the results and suitability of two different approaches to the treatment of post-conization International Federation of Gynaecology and Obstetrics (FIGO) stage IA1 cervical carcinoma: a more radical approach, directly scheduling a second surgery versus a more conservative one, which consists of performing a cotest (PAP plus HPV-test) in a follow-up visit and deciding whether to apply a second surgery on the basis of the results. Retrospective descriptive study including 144 cases of stage IA1 cervical carcinoma diagnosed after a loop electrosurgical excisional procedure (conization), between 1987 and 2019 in the Mother-and-Child University Hospital of Gran Canaria (Spain). Selected patients were split into two groups for analysis: patients directly undergoing a second surgical intervention (hysterectomy or re-conization) after diagnosis and patients who were followed-up before making a decision whether to schedule a second surgery or continue to follow-up. 75% of women directly receiving a second surgical intervention (no post-conization follow-up) underwent hysterectomy, while 25% underwent re-conization. Histological outcomes from hysterectomized patients showed 65% negative results for intraepithelial lesions, 9% low-grade squamous intraepithelial lesions (LSIL), 16% high-grade squamous intraepithelial lesions (HSIL) and only 10.5% confirmed invasive lesions: hysterectomy complication rate was 7%. Histological studies from women subjected to re-conization showed 32% negative results, 37% LSIL, 5% HSIL and 26% malignancy. In the group of patients who were followed-up after diagnosis, 8.8% needed a second intervention; none of them showed negative histological results, while 100% hysterectomized and 25% patients with re-conization showed HSIL. No unnecessary hysterectomy procedures were conducted in this group. HPV-16 was the most common genotype in both groups. Conization proved to be a suitable alternative to hysterectomy as a treatment for post-conization stage IA1 cervical cancer. Our results showed that 65% hysterectomy procedures conducted without previously monitoring for residual disease corresponded to negative results and were therefore, unnecessary. We conclude that confirmation of the presence of residual disease by using cotest is essential to make a decision on further treatment and that a conservative management is often possible and, in our opinion, preferable.

High-Grade Squamous Intraepithelial Lesion of the Cervix -- Treatment / Management

Women aged 21 to 24 with HSIL cytology are recommended to undergo colposcopy. If CIN 2 or greater is not diagnosed on biopsy, it is recommended the patient follow up with cytology and colposcopy every 6 months for a 24-month period, as long as exams are adequate and reveal no squamous intraepithelial lesions (or at most LSIL). If HSIL cytology or a high-grade colposcopic lesion is found during this time, a biopsy should be performed. In patients where HSIL cytology persists for 24 months but no high-grade lesion is identified on biopsy, a diagnostic excisional procedure is recommended. If colposcopy is inadequate, CIN 3 is specified on biopsy, or CIN 2 or CIN 3 persists for 24 months, a diagnostic excisional procedure is recommended. If CIN 2 is specified on biopsy, observation for 12 months using both cytology and colposcopy every 6 months is recommended. This guideline exists because CIN 2 has a higher regression rate and less risk of progression to cancer than CIN 3, especially in younger women. Once the patient has 2 consecutive negative results on cytology and no evidence of a colposcopic abnormality, co-testing is recommended a year later. If negative, a second co-test is recommended after three years. If either co-test is abnormal, colposcopy is recommended.

Squamous intraepithelial lesion

A squamous intraepithelial lesion (SIL) is an abnormal growth of epithelial cells on the surface of the cervix, commonly called squamous cells. This condition can lead to cervical cancer, but can be diagnosed using a Pap smear or a colposcopy. It can be treated by using methods that remove the abnormal cells, allowing normal cells to grow in their place. In the Bethesda system, the cytology can be graded as LSIL (low-grade squamous intraepithelial lesion) or HSIL (high-grade squamous intraepithelial lesion). References Papillomavirus-associated diseases

Colposcopy as a method of management strategy in CIN and microinvasive cancer.

During nearly 40 years of using colposcopy, an original management strategy in CIN and early cervical cancer was developed and confirmed in 2 study groups of cervical lesions containing respectively 1228 and 6001 cases. This approach is based on colposcopy as the main method in early detection of CIN and cancer, with supplementary cytology in necessary cases, and on a coloposcopic-histological staging of these lesions for treatment qualification. Colposcopy alone is a fairly adequate method for diagnosis of 60% of examined cases, and coloscopy with directed biopsy in the next 20% of colposcopically highly suspect findings. Only in the remaining 20% of colposcopically less suspect findings and in the cases of "unsatisfactory colposcopy", supplementary was cytology required. In this study colposcopy findings connected with histological evaluation of the specimens provided a basic way for determining the advancement of processes and the selection method for the appropriate type and extent of treatment. CIN 1 and 2 and small focuses of CIN 3 including CIS entirely visible on the ectocervix, in childless young women were treated by cryosurgery. In all remaining cases of CIN 3, the basic therapeutic method was cold-knife conization. In exceptional cases simple hysterectomy can be a more adequate treatment. Depending on our colposcopic-histological staging, in Stage IA1--conization, whereas in Stage IA2--a moderately extended hysterectomy should be optionally performed. The management strategy introduced is an economical, fully effective and quick way of detection and selection of the method for the treatment of CIN and early cervical cancer.

Results of a randomized trial on the management of cytology interpretations of atypical squamous cells of undetermined significance.

This study was undertaken to compare alternative strategies for the initial management of a cytologic diagnosis of atypical squamous cells of undetermined significance (ASCUS). A total of 3488 women with a community-based ASCUS interpretation were randomly assigned to immediate colposcopy, triage that was based on enrollment HPV DNA testing and liquid-based cytology at a colposcopy referral threshold of high-grade squamous intraepithelial lesion (HSIL), or conservative management based on repeat cytology at a referral threshold of HSIL. All arms included 2 years of semiannual follow-up and colposcopy at exit. Loop electrosurgical excision procedure was offered to women with histologic diagnoses of cervical intraepithelial neoplasia (CIN) grade 2 or 3 at any visit or persistent CIN grade 1 at exit. The study end point was 2-year cumulative diagnosis of CIN grade 3. The 2-year cumulative diagnosis of CIN grade 3 was 8% to 9% in all study arms. The immediate colposcopy strategy yielded 53.6% sensitivity for cumulative cases of CIN grade 3 diagnosed over 2 years. The human papillomavirus (HPV) triage strategy referred 55.6% of women and detected 72.3% of cumulative cases of CIN grade 3. A conservative management strategy of repeat cytology at the HSIL threshold referred 12.3% of women while detecting 54.6% of cumulative CIN grade 3. To compare triage tests, we re-estimated the performance of HPV and cytology in successfully referring women with underlying CIN grade 3 (ie, ignoring the insensitivity we discovered in colposcopically directed biopsies). A single enrollment HPV test identified 92.4% of the women diagnosed with CIN grade 3. Serial cytology, even at an ASCUS threshold, would have required two visits to achieve similar sensitivity (95.4%) and would have referred 67.1% to colposcopy. HPV triage is at least as sensitive as immediate colposcopy for detecting CIN grade 3 and refers about half as many women to colposcopy. Follow-up that used repeat cytology is sensitive at an ASCUS referral threshold but requires two follow-up visits and ultimately more colposcopic examinations than HPV triage.

[The value of vaginal cytology after total hysterectomy for benign or malignant lesions (author's transl)].

The necessity of vaginal stump smears is demonstrated by way of 1773 smears taken from 846 hysterectomized patients. In 1,18 per cent of cases operated for benign indications there are found pathological changes on the vaginal end; 7,5 percent pathological neoplastic deformations are found following hysterectomy for carcinoma in situ; recurrences of cervical, corpus- and ovarial carcinomata are detected by vaginal stump smears at an early data. The leaving of a vaginal cuff is discussed as being responsible for the increased occurrence of new malignant growth following carcinoma in stu-operations. The other results are compared with those stated in literature.

Gynecology_Novak

2. At 24-months, those with ASC-US or greater should be referred. 3. Prospective follow-up by HPV DNA testing in this age group is not useful because of the high rate of positive results. 1. Both excisional and ablative procedures are acceptable treatment modalities for women with histologically proven CIN 2 or 3 with satisfactory colposcopy (Fig. 19.16D). An excisional procedure is recommended for residual/recurrent CIN 2 or 3. 2. Ablation is unacceptable for women with a histologic diagnosis of CIN 2 or 3 and unsatisfactory colposcopy. 3. Cytologic and colposcopic follow-up of CIN 2 or 3 is necessary only in specific circumstances. Acceptable posttreatment follow-up options include cytology alone, every 6 months, combined cytology and colposcopy every 6 months, and HPV DNA testing at 6 to 12 months. 4. If HPV DNA testing is positive or if the repeat cytology is ASC-US or greater, referral for colposcopy and endocervical sampling is recommended. 5.

Clinical implication of atypical squamous cells of undetermined significance with or without favoring high-grade squamous intraepithelial lesion on cervical smears.

The cytologic diagnosis of atypical squamous cells of undetermined significance (ASCUS) on a cervical smear usually makes clinicians unsure of how to manage the patient and follow-up on her condition. We attempted to define the clinical implication of qualifying the cytologic diagnosis of ASCUS as either favoring a high-grade squamous intraepithelial lesion (HSIL) or not in an effort to provide management guidelines. From January through May 1997, 65 of 5792 women who had cervical/vaginal smears taken at Kaohsiung Chang Gung Memorial Hospital were diagnosed as having ASCUS. Thirteen of the 65 cases of ASCUS favored an HSIL, based on nuclear abnormalities in atypical metaplastic and parakeratotic-type squamous cells. All these 65 patients were evaluated in our outpatient clinic by a second cervical smear, colposcopy, and colposcopically directed biopsies and/or endocervical curettage. The median length of the follow-up period was 19 months (range, 16 to 21 months). Of the 52 patients evaluated for ASCUS smears without favoring HSIL, 6 (11.5%) had a low-grade SIL (LSIL), 1 (1.9%) had cervical intraepithelial neoplasia grade II (CIN II), and 1 (1.9%) had invasive squamous carcinoma. Of the 13 patients with a cervical cytologic diagnosis of ASCUS favoring HSIL, 1 (7.6%) had immature metaplasia, 2 (15.4%) had LSIL, 2 (15.4%) had CIN II, 6 (46.2%) had CIN III, and 2 (15.4%) had invasive squamous carcinoma. For patients with a cytologic diagnosis of ASCUS favoring HSIL, more aggressive interventions, such as colposcopy-directed biopsy, endocervical curettage, or even conization, should be performed promptly. However, those without features favoring HSIL may be evaluated with regularly repeated smears.

Cartwright Inquiry

of microinvasion. This was at a time when there was ample scientific reason for concern about the damage caused by hysterectomy or cone biopsy and uncertainty about whether immediate use of these procedures was automatically the best thing to do for symptomless lesions, particularly in young women who might want children. Green's practice, although motivated by a desire to avoid unnecessary and damaging interventions in symptomless women, was easy for others to condemn due to the lack of any relevant policy, research, or ethical framework for cervical screening at that time.' The Case study authors note that the number of women managed by limited biopsy alone is shown in Appendix 3 of the Inquiry Report. There were 5 patients managed by limited biopsy only, with no evidence given as to whether any of these 5 patients suffered harm as a result.

Gynecology_Novak

4. If HPV DNA testing is positive or if the repeat cytology is ASC-US or greater, referral for colposcopy and endocervical sampling is recommended. 5. If HPV DNA testing is negative or if two consecutive posttreatment cytology results are negative for intraepithelial lesion or malignancy, routine screening for at least 20 years is recommended, and should be annual for at least 5 years. A negative HPV DNA test is an excellent predictor of a normal posttreatment for CIN 2 or 3. 6. If CIN 2 or 3 is histologically found at the margins of an excised specimen or in an endocervical sample obtained immediately after the procedure, cytologic follow-up with endocervical sampling every 4 to 6 months is preferred. The role of colposcopy in this follow-up option is not clearly defined in the Guidelines, although in practice, cytology and colposcopy will be performed in most clinical settings. 7.

Neoplasia associated with atypical glandular cells of undetermined significance on cervical cytology.

The clinical importance of atypical glandular cells of undetermined significance (AGUS) on cervicovaginal smear has not been well defined. Between January 1990 and April 1996, 127 smears were reported as showing AGUS changes by the cytopathology division at the University of Massachusetts Medical Center. The medical records of these women were reviewed: 17 women were excluded because of previous hysterectomy or gynecologic cancer, 85 were biopsied, 16 were followed by repeat smears, and 9 were lost to follow-up. Forty-four women had negative biopsies or cervicitis. There were 15 endometrial lesions: 10 hyperplasias (2 with atypia) and 5 adenocarcinomas. Twenty-five women had cervix lesions including 3 endocervical atypias, 12 low-grade cervical intraepithelial neoplasia (CIN), 6 high-grade CIN, one adenocarcinoma in situ, and 3 invasive adenocarcinomas. One patient had ovarian cancer. Two of the 16 women followed by repeat pap smear eventually had a cancer diagnosis: one with cervix cancer and one with colon cancer. We were unable to identify a subgroup of women with AGUS who were at increased risk for serious pathology when we compared multiple demographic variables, symptoms, or the presence of coexistent squamous abnormalities on cervical cytology. The mean age of the 15 women with endometrial lesions was 59.9 years, which was significantly older than those patients with cervix lesions who had a mean age of 38.9 years. The presence of AGUS on cervical cytology is a marker for significant gynecologic neoplasia and should be investigated with colposcopically directed biopsies, endocervical curettage, and, in older women, endometrial biopsy.