According to the SEGO: "Excise the entire lesion so that it can be evaluated histologically. It involves excision of the entire transformation zone. In general, the excision should be adapted to the size and characteristics of the lesion. Three types of excision are distinguished according to the presence of the endocervical component of the lesion. Excision type 1 (applicable in cases with transformation zone type 1, in which the diathermic loop should not include endocervical canal or exceed 8 mm in depth), excision type 2 (indicated in transformation zones type 2, involves resecting a small part of endocervical canal visible by colposcopy) and excision type 3 (indicated in transformation zones type 3, includes part of endocervical epithelium)". When they speak of excision, it is synonymous with conization; as the lesion is less than 8mm deep, this is the indicated treatment.

According to the SEGO: "Excise the entire lesion so that it can be evaluated histologically. It involves excision of the entire transformation zone. In general, the excision should be adapted to the size and characteristics of the lesion. Three types of excision are distinguished according to the presence of the endocervical component of the lesion. Excision type 1 (applicable in cases with transformation zone type 1, in which the diathermic loop should not include endocervical canal or exceed 8 mm in depth), excision type 2 (indicated in transformation zones type 2, involves resecting a small part of endocervical canal visible by colposcopy) and excision type 3 (indicated in transformation zones type 3, includes part of endocervical epithelium)". When they speak of excision, it is synonymous with conization; as the lesion is less than 8mm deep, [HIDDEN].

34-year-old woman who consults for repeated coitorragia. She brings a cytology with a high grade intraepithelial lesion (U-SIL). Subsequently, colposcopy and biopsy were performed on a mosaic area and histology showed a focus of invasive squamous cell carcinoma of 2 mm in length. Which therapeutic option is the most appropriate for this patient?

Pelvic radiotherapy with curative intent.

[A falsely reassuring cervical smear in adenocarcinoma of the external os].

3 women with only mild changes in cervical smears were later found to be suffering from cervical adenocarcinoma. The first patient was 53 years old. Her smears repeatedly showed Pap 3 with moderately atypical glandular cells. After 3 colposcopic examinations with biopsies and 2 loop electrosurgical excision procedures of the cervix which showed no histological signs of malignancy, diagnostic conization revealed an adenocarcinoma of the endocervix. She underwent a radical hysterectomy and chemoradiation because of positive pelvic nodes. The second patient was 30 years old and had persistent vaginal discharge and an enlarged cervix, but no cytological abnormalities. Colposcopy was unsatisfactory and the tissue obtained by loop electrosurgical excision was normal. Adenocarcinoma was diagnosed after conization. She was treated with radical hysterectomy and radiotherapy but died after one year. The third patient, aged 26, had a long history of slightly abnormal Pap smears and vulvar condylomata, and was referred with vaginal discharge. A severe abnormal smear with glandular atypia was followed by colposcopical biopsies and conization, which revealed an endocervical adenocarcinoma. She underwent radical hysterectomy. Adenocarcinoma is a rare type of cervical cancer: III cases out of 584 patients with cervical cancer in 2003 in the Netherlands. This neoplasm is more difficult to detect than cervical squamous cell carcinoma. Cervical cytology is not an effective tool for screening and diagnosis. Due to the localization, multifocality and diversity in its presentation, the assessment of cytology has a high false-negative percentage. Screening may be enhanced by combining cytology with testing for high-risk HPV types, notably type 18. If cervical cytology shows persistent atypical glandular cells with no conclusive histological result, then due to the endocervical localisation of the lesions adenocarcinoma can only be excluded by conization.

Recurrent vaginal intraepithelial neoplasia successfully treated with topical imiquimod: A case report.

Vaginal intraepithelial neoplasia (VAIN) is a rare disease associated with human papillomavirus infection. High-grade VAIN is typically treated with either excisional or ablative therapy. However, recurrent VAIN lesions are common and these treatments cause vaginal scarring. Recent studies have indicated that 5% imiquimod is an effective treatment for VAIN. The present report describes a case of a woman diagnosed with recurrent VAIN 3 who was treated with a 5% topical imiquimod cream and achieved a complete response after excision and CO<sub2</sub laser vaporization. A 53-year-old, gravida 5, para 2 postmenopausal woman who was diagnosed with papillary squamous cell carcinoma by biopsy underwent conization, total abdominal hysterectomy and bilateral salpingo-oophorectomy. A histological examination revealed grade 3 cervical intraepithelial neoplasia with free surgical margins. At 3 years after the hysterectomy, the vaginal smear revealed atypical squamous cells, leading to a pathological diagnosis of VAIN 3. Partial vaginectomy was performed, and VAIN 3 was detected in the lesion with positive margins. At 4 months into follow-up, the vaginal smear revealed a high-grade squamous intraepithelial lesion (HSIL), and subsequent biopsy during colposcopy revealed a pathological diagnosis of VAIN 3. At 3 months after CO<sub2</sub laser vaporization, the vaginal smear revealed HSIL with suspected recurrence and imiquimod treatment was initiated. One sachet of 5% imiquimod cream (0.25 g) was placed in the entire vagina three times per week for 14 weeks with no apparent complications. At 3 years after the treatment, there has been no recurrence. This case demonstrated that topical imiquimod with careful follow-up is an effective treatment for VAIN and is well-tolerated. Further clinical evidence of the effectiveness and safety of imiquimod in patients diagnosed with VAIN is required.

Random biopsy after colposcopy-directed biopsy improves the diagnosis of cervical intraepithelial neoplasia grade 2 or worse.

To evaluate the usefulness of additional random biopsies in the diagnosis of cervical intraepithelial neoplasia grade 2 (CIN 2) or worse (CIN 2+) after colposcopy-directed biopsy. A retrospective chart review was performed in 107 women with satisfactory colposcopy results after colposcopy-directed biopsy with random biopsy for abnormal cervical cytological evaluation at Soonchunhyang University Hospital between April 2008 and November 2009. Random biopsies were performed at the cervical squamocolumnar junction in lesion-free quadrants of the cervix. Loop electrosurgical excision procedure conizations were performed in 59 women. Age, referral cytology, lesion size, human papilloma virus (HPV) viral load, and HPV type were analyzed as possible indicators of lesion severity detected using random biopsy. The mean age was 39.3 years (range = 21-72 y), and 96 (89.7%) women were premenopausal. Sixty-three women had CIN 2+; of those, 8 (12.7%) were diagnosed using random biopsies: 6 had high-grade squamous intraepithelial lesions; 1 had low-grade squamous intraepithelial lesions; and 1 had atypical squamous cells of undetermined significance. Lesions diagnosed as CIN 2+ using random biopsies were significantly correlated with high-grade cytology (p <.001) and lesion size (p <.001) but not age (cutoff = 40 years), HPV viral load (cutoff = 300 relative light units; Hybrid Capture 2), or HPV genotype. Of 59 patients who underwent loop electrosurgical excision procedure conization, the disease severity of 9 (15.3%) cases was upgraded 1 or more grades, compared with the punch biopsy results. The detection of CIN 2+, particularly high-grade cytological abnormalities and large lesion size, can be increased by additional random biopsies after satisfactory colposcopy. Loop electrosurgical excision procedure conization can detect lesions not detected by punch biopsy.

Prognostic factors for the development of vaginal intraepithelial neoplasia.

To identify risk factors for the appearance of vaginal intraepithelial neoplasia (VAIN). A total of 485 women with abnormal cytologies were followed over three years (2003-2006). They underwent cytolology and colposcopy, and testing for human papillomavirus virus (HPV) infection. If the colposcopy was atypical, a biopsy was performed. A total of 256 women were treated: 161 by cone biopsy, 103 by LLETZ, 12 by repeat conization, and 44 by total hysterectomy. In eight cases VAIN was diagnosed following hysterectomy. The average age at which VAIN appeared was 49.8 years (age range 39-61). Hysterectomy was indicated in two cases of cervical cancer, four cases of persistent high-grade cervical SIL, and two cases of recurrent high-grade cervical SIL. The mean time for the appearance of VAIN following hysterectomy was 3.8 years (range 1-9 years). Of these eight women, seven had HPV infections at high risk for carcinogenesis. Long-term follow-up cytology is necessary for women treated for high-grade SIL, even after hysterectomy, because of the increased risk of a primary vaginal VAIN lesion, especially in women with high-risk HPV infection.

Follow-up by combined cytology and human papillomavirus testing for patients post-cone biopsy: results of a long-term follow-up.

The goal of this study was to evaluate the clinical implications of integrating human papillomavirus (HPV) testing into a long-term follow-up and management protocol for women postconization for high-grade cervical intraepithelial neoplasia (CIN2-3). Sixty-seven women were followed-up by Pap smears and HPV type and load testing (mean follow-up, 63 months; range, 50-72). Patients with persistent abnormal cytology on two consecutive smears and those with positive HPV test results (whatever their cytologic findings) were referred for colposcopy-directed biopsy. Patients histologically diagnosed with CIN2-3 and those with high-load HPV (whatever their histologic findings) underwent repeat conization or hysterectomy for residual disease. At follow-up, 29 (43.2%) women had positive cytology or positive HPV results and were referred for colposcopy. Eleven (37.9%) had high-grade cervical intraepithelial neoplasia or high-load HPV results and were further treated by reconization/hysterectomy. The respective positive predictive values of high-load HPV and low-grade squamous intraepithelial lesions were 100 and 60% for any CIN and 90 and 15% for CIN2-3. Only five of nine cases with a final diagnosis of CIN2-3 were originally identified by cytology: the other four were detected only by parallel evaluation by HPV testing. High-load HPV results with normal cytology or low-grade lesions harbored an 80% risk for CIN2-3. Adding HPV load assessment to the follow-up protocol of women postconization due to CIN2-3 lesions could help detect high-grade residual disease among low-grade lesions and normal cytology cases while concomitantly and safely bestowing the advantage of lowering the rates of colposcopic referrals and surgical procedures.

[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.

Carcinoma-in-situ of the cerivix treated with colposcopy guided epithelial conization. Report of a 4-7 year follow-up study.

Twenty-five patients with the diagnosis of carcinoma-in-situ (CIS) of the cervix were treated with colposcopy guided epithelial conization. During the follow-up study of 4-7 years' duration, there was no recurrence of CIS in 20 of the 25 patients. Between 6 and 12 months after conization, 3 patients showed recurrence of CIS. Two of these patients were treated with further epithelial conization with no evidence of further recurrence 4 years after the second treatment. The third  patient refused to accept further epithelial conization and modified radical hysterectomy was done without any evidence of residual tumour in the hysterectomy specimen. One patient showed stromal invasion in both colposcopically guided biopsy and bone biopsy. Modified radical hysterectomy specimen showed remnants of stromal invasion. One patient with Class IV smear failed to show any atypical transformation zone and cervicitis was proven on colposcopy guided biopsy following treatment with Flagyl. For two of the 25 patients, cytology was Class II and therefore failed to diagnose the pre-malignant condition; but colposcopy showed a grade 3 atypical transformation zone and the presence of CIS was confirmed histologically. Simultaneous use of cytology, colposcopy and colposcopically guided biopsy confirmed the diagnosis of CIS in all cases. The authors recommend colposcopically guided epithelial conization in younger patients, provided the malignant lesion is strictly intra-epithelial, and limited to the ectocervix. Routine follow-up with the aid of cyto-colposcopy remains the key factor in this schedule of therapy.

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.

[Recurrent carcinoma in situ of the uterine cervix (author's transl)].

Among 228 patients who had previous treatment for carcinoma in situ of the cervix, most by hysterectomy, 3 recurrences in vaginal stumps were detected in women age 36, 46, and 56. In another case a carcinoma in situ of the cervix was found in a 25 year old patient who had a diagnostic and therapeutic conization because of desire for childbearing. The histology of the cone showed no residual carcinoma. Concommitent to the recurrent carcinoma in situ of the cervix a carcinoma of the vulva was detected. Recurrences of carcinoma in situ could occur because of incomplete resection of primary lesion. Wrong classification in the laboratory is possible if the invasion is missed on the microscopic examination and the case therefore receives the wrong treatment. Recurrences which are not true recurrences could arise from multicentric atypical foci of the squamous epitheleum of the -ower female genital tract. These considerations lead to the following recommendations: 1. When the suspected diagnosis carcinoma in situ of the uterine cervix is made a large enough cone biopsy which is appropriately marked is obtained and a complete microscopic examination of the cone must be obtained. 2. A hysterectomy with a large vaginal cuff is the treatment of choice. 3. A careful workup of the operative specimen in the microscopic laboratory is expecially essential. 4. A patient with such previous treatment for carcinoma in situ of the uterine cervix must be urged to continue with regular preventive examinations for cancer. The vaginal stump must be regularly re-examined both by colposcopy and by cytology.

[Therapeutic results of conization with diathermy].

To assess the frequency, histological grade and time interval of residual and recurrent lesions after loop electrosurgical excision procedure and to analyse their associated risk factors. 288 patients treated by loop electrosurgical excision procedure between February 1991 and July 1995 were prospectively included in this study. They agreed to a postoperative cytological and colposcopic follow-up with a first visit between 3 and 6 months after excision, a second one between 9 and 15 months and a third one between 24 and 36 months. We used univariate and multivariate analyses to evaluate the association between clinical variables and residual or recurrent lesions. The pathologic diagnosis of the specimens included 21 normal cervices (7.3%), 35 CIN 1 (12.2%), 43 CIN 2 (14.9%), 180 CIN 3 (62.5%), 1 adenocarcinoma in situ (0.3%) and 8 microinvasive cancers (2.8%). The pathologist considered the excision complete in 244 cases (85%). Among the other 44 patients, 27 had involved endocervical margins, 17 involved exocervical margins but none had both margins involved. The mean postoperative follow-up +/- standard deviation was 39 +/- 13 months (range 24-68 months). Treatment failure, defined as the persistence or recurrence of a cervical lesion, was observed in 20 patients (6.9%) having a squamous cancer stage IB (n = 1), a CIN 3 (n = 15), an adenocarcinoma in situ (n = 1) or a CIN 1 (n = 1). In 6 cases the second treatment was performed before the first cytological and colposcopic visit because of an excision considered incomplete by the pathologist. Overall 19 out of the 20 treatment failures were diagnosed within the first two years of the follow-up. The endocervical localisation of the initial lesion (adjusted RR 13.7; 95% CI 1.3, 150.1; P < 0.05) and incomplete excision (adjusted RR 9.1; 95% CI 3.0, 27.3; P < 0.001) were the only independent risk factors for treatment failure. Residual or recurrent lesions occurs rarely after loop electrosurgical excision procedure. They are favoured by totally endocervical lesion and an incomplete excision. With the association of cytology and colposcopy, 95% of treatment failures can be detected in the first 2 postoperative years.

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.

Positive endocervical margins at conization: repeat conization or colposcopic follow-up? A retrospective study.

The presence of residual cervical lesions was evaluated in patients submitted to repeat conization due to a finding of positive endocervical margins in a previous loop electrosurgical excision procedure (LEEP) specimen. In addition, the correlation between the presence of a residual lesion and risk factors for cervical cancer, and the use of repeat conization as first-choice treatment were analyzed. This retrospective study included 44 patients submitted to repeat cervical conization or total hysterectomy following a finding of affected endocervical margins in LEEP specimens. The risk factors analyzed in relation to the presence of residual lesions were age, smoking, cone depth, glandular involvement and the histopathology findings of cervical intraepithelial neoplasia (CIN) 1, CIN 2 or CIN 3/carcinoma in situ. The Chi-square test and the Mann-Whitney t-test were used, with significance defined at P < 0.05. Residual lesions were found in 23/44 patients (52.3%), with 3/23 cases (13.0%) being compatible with invasive squamous cell carcinoma. Of the 23 patients, six (26.1%) were submitted to total hysterectomy, with one case being compatible with a moderately differentiated invasive squamous cell carcinoma. Two patients with a histopathology finding of CIN 3/carcinoma in situ in the previous LEEP specimen were diagnosed with invasive squamous cell carcinoma in the repeat conization specimen. Residual lesions were not significantly associated with the risk factors evaluated. In view of the high frequency of residual disease found when positive endocervical margins were found in LEEP specimens, the indication for repeat cervical conization rather than colposcopic follow-up is viable and justified. Indeed, since the presence of a residual lesion and its progression in the cervical canal are more difficult to screen and control, patients unable to comply with regular colposcopic follow-up could benefit from repeat conization when trying to avoid a potentially negative outcome.

Human papilloma virus testing in patient follow-up post cone biopsy due to high-grade cervical intraepithelial neoplasia.

We evaluated the contribution of the human papilloma virus (HPV) load in planning follow-up and management of women post cone biopsy for high-grade cervical intraepithelial neoplasia (CIN2-3). Ninety-six suitable women were followed-up by Pap smears: two consecutive abnormal smears dictated referral for colposcopy-directed biopsy. Before colposcopy, HPV tests determined high-risk HPV DNA type and load (Hybrid Capture System type I). Patients histologically diagnosed with CIN1 or CIN2-3 underwent repeat conization or hysterectomy for residual disease. HPV load was compared to cytology for the detection of residual disease. At follow-up, 20/89 (22.4%) studied women had positive cytology reports of either low- (n = 11) or high-grade (n = 9) squamous intraepithelial lesion (SIL). Colposcopic biopsies diagnosed 9 CIN1 and 8 CIN2-3 cases. Residual disease was corroborated in 16/17 (94.1%) women and the status was readjusted based on cone biopsy/hysterectomy: CIN2-3 in 9 and CIN1 in 7. The positive prediction values for CIN2-3 residual disease with high-grade SIL, CIN2-3 on colposcopic punch biopsy, and high HPV load were 89, 100, and 100%, respectively. For CIN1 residual disease with low-grade SIL, CIN1 on colposcopic punch biopsy, and low and borderline HPV load, they were 54.5, 77.7, and 100%. The HPV load was a more accurate predictor for CIN1 or CIN2-3 on the cervical specimen in cases with low-grade SIL or CIN1 on colposcopic biopsy. Evaluating HPV loads after a positive cytology report may assist in triaging women post conization biopsy for CIN2-3 to appropriate treatment. Its high positive predictive value, specificity, and sensitivity for CIN1 and CIN2-3 and supplementary information could be especially pertinent for clinical management of low-grade SIL cases.

20-year experience of follow-up of the abnormal smear with colposcopy and histology and treatment by conization or cryosurgery.

During the period 1967 to 1977, 1466 women with Pap smears suggesting cervical epithelial neoplasia (CIN) II or worse were evaluated by colposcopy, portio biopsy, and endocervical curettage. Women who had CIN III were treated first by conization and later by cryosurgery. Cytological diagnosis was inaccurate compared to colposcopical and histological diagnosis, with 27% having a worse histological diagnosis. In 22% of the cases histology was two degrees less or worse than suggested by cytology. Presence of atypical vessels was associated with invasive cancer in 17% of cases. A total of 635 patients were treated by conization. After an average follow-up of 10 years, the cure rate was 96% compared to 87% by cryosurgery (104 cases). Hysterectomy was, mainly because of old age, performed on 154 patients; the cure rate was 97%. Although most treatment failures occurred within the first 5 years, some were seen after as long as 15-20 years.

Diagnostic and therapeutic viewpoints on cervical intraepithelial neoplasia. 10-Year follow-up of a conization material.

In 429 women with the diagnosis of cancer in situ (CIS), we found, during a follow-up time of 10 years, a relapse frequency of 5.3%; conization was the primary treatment in 414 cases, in 13 cases hysterectomy and radiotherapy in 2 cases. We found that the mean age was significantly higher (p less than 0.01) when the primary CIS lesion was localized in the cervix (36.8 +/- 10.5) compared to localization only on the portio (31.3 +/- 8.7). The risk of relapse was significantly higher (p less than 0.05) in patients where the primary cone had the lesion localized in the cervix compared to the patients where the primary cone had the lesion localized only to the portio. We found that the localization of PAD relapses appearing later compared to a high degree (about 65%) with the localization of the primary CIS lesion. Vaginal relapse was, generally speaking, twice as common when the primary CIS lesion was localized in the cervix compared to when it was localized on the portio alone. Alternative treatment methods to the conization operation are discussed and an increased individualization of CIS treatment is emphasized particularly with consideration to age and the localization of the CIS lesion.

European guidelines for quality assurance in cervical cancer screening: recommendations for clinical management of abnormal cervical cytology, part 1.

The current paper presents the first part of Chapter 6 of the second edition of the European Guidelines for Quality Assurance in Cervical Cancer Screening. It provides guidance on how to manage women with abnormal cervical cytology. Throughout this article the Bethesda system is used for cervical cytology terminology, as the European guidelines have recommended that all systems should at least be translated into that terminology while cervical intraepithelial neoplasia (CIN) is used for histological biopsies (Cytopathology 2007; 18:213-9). A woman with a high-grade cytological lesion, a repeated low-grade lesion or with an equivocal cytology result and a positive human papillomavirus (HPV) test should be referred for colposcopy. The role of the colposcopist is to identify the source of the abnormal cells and to make an informed decision as to whether or not any treatment is required. If a patient requires treatment the colposcopist will decide which is the most appropriate method of treatment for each individual woman. The colposcopist should also organize appropriate follow-up for each woman seen. Reflex testing for high-risk HPV types of women with atypical squamous cells (ASC) of undetermined significance with referral for colposcopy of women who test positive is a first option. Repeat cytology is a second possibility. Direct referral to a gynaecologist should be restricted to special circumstances. Follow-up of low-grade squamous intraepithelial lesion is more difficult because currently there is no evidence to support any method of management as being optimal; repeat cytology and colposcopy are options, but HPV testing is not sufficiently selective, unless for older women. Women with high-grade squamous intraepithelial lesion (HSIL) or atypical squamous cells, cannot exclude HSIL (ASC-H) should be referred without triage. Women with glandular lesions require particular attention. In a subsequent issue of Cytopathology, the second part of Chapter 6 will be presented, with recommendations for management and treatment of histologically confirmed intraepithelial neoplasia and guidance for follow-up of special cases such as women who are pregnant, postmenopausal or immunocompromised.

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.

Usefulness of repeat cytology at the time of first colposcopy.

The value of repeat cytology in the detection of high-grade preinvasive or invasive disease was analyzed at the time of colposcopy in cases of patients with abnormal referral cytology. A series of 136 patients with squamous abnormalities in their referral cytology, who had undergone repeat cytology and for whom outcome had been established, were included in the study. Final diagnosis consisted of 27 negative results (20%), 37 cases of CIN1 (27%), 31 CIN2 (23%), 39 CIN3 (29%), and 2 (1%) cases of squamous cell carcinoma (SCC). Referral and repeat cytology suggestive of atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H), high-grade squamous intraepithelial lesion (HSIL) were findings significantly associated with a final diagnosis of CIN2 or worse. Sensitivity and positive predictive value of repeat cytology for the histological diagnosis of significant histological neoplasia (CIN2 or worse) were 81.9% and 77.6%, respectively. In women with referral cytology findings of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion (ASC-US/LSIL), repeat cytology was suggestive of HSIL in 20% of cases (11/54), and in 4% (2/54) biopsy was negative or CIN1, and the final diagnosis established by LLETZ was CIN3. Eight cases (10%) of HSIL in referral and repeat cytology in which biopsies were negative or insufficient were diagnosed as CIN3 or worse in the final diagnosis. Repeat cytology would have changed therapeutic management in 4 and 10%, respectively, of patients included as ASC-US/LSIL and ASC-H/HSIL in referral cytology.

[Conization with positive margins: what strategy should be adopted?].

To define recommended treatment in cases of positive margins on cone biopsy specimens. This single-center retrospective study concerned 220 conizations performed between January 1996 and June 1998. The results of 70 conizations (31.8%) with positive margins were analysed. There were 32 cold knife conizations (mean age: 43 years) and 38 conizations by the loop electrosurgical excision procedure (mean age: 33 years). Mean depth of conization was 15.94 mm for cold knife conization and 10.08 mm for loop electrosurgical conization. Fifteen patients were excluded (5 with invasive cancer and 10 were lost to follow-up). This study included 55 patients with a mean 12-month follow-up. Six underwent hysterectomy for mini-invasion on the specimen or advanced age. Eleven underwent a second conization (followed by hysterectomy in 2 cases). The other 38 patients were submitted to simple surveillance with cervico-vaginal cytology and colposcopic examination. The rate of residual lesions (cervical intra-epithelial neoplasia: CIN 3) after conization with positive margin was 14.5% (n = 8). Residual persistent dysplasia is not present in all patients after conization with positive margins. Cytology and colposcopy allow detection of dysplasia, indicating the need for a second conization. In women with no desire for further pregnancy, systematic repeat surgery must be recommended.

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.

A Large Retrospective Study of 12714 Cases of LEEP Conization Focusing on Cervical Cancer That Colposcopy-Directed Biopsy Failed to Detect.

Punch biopsy is important in the diagnosis of cervical cancer. However, it may fail to detect early cervical cancers. A retrospective study was performed in the largest academic women's hospital in China to demonstrate cervical cancer that colposcopy-directed biopsy failed to detect. <iMethods</i. Patients who were diagnosed with high-grade squamous intraepithelial lesion (HSIL), adenocarcinoma in situ (AIS), and persistent low-grade squamous intraepithelial lesion (LSIL) via colposcopy-directed biopsy and had further undergone loop electrosurgical excision procedure (LEEP) conization were included. These procedures were performed at Obstetrics and Gynecology Hospital of Fudan University from July 1, 2013, to December 31, 2016. In total, 5.98% (760/12714) of patients who underwent conization were diagnosed with invasive cervical cancer. Persistent LSIL (0.24%), HSIL (6.37%), and AIS (24.31%) were detected cancer by conization. Histological subtypes included squamous cell carcinoma (92.0%), adenocarcinoma (5.1%), adenosquamous carcinoma (1.8%), adenoid basal type carcinoma (0.9%), and small cell neuroendocrine carcinoma (0.1%). Cytology reports consisted of HSIL (45.4%), atypical squamous cells of undetermined significance (ASC-US) (16.1%), and LSIL (11.6%), and atypical squamous cells cannot exclude HSIL (ASC-H) (9.3%), squamous cell carcinoma (0.9%), AGC (atypical glandular cells, 0.9%), AIS (0.4%), and NILM (negative for intraepithelial lesion or malignancy, 15.4%). The sensitivity of high-risk human papillomavirus (hrHPV) screening (96.4%) was significantly higher than that of cytology (84.6%) (<iP</i < 0.01), with sensitivity of cotesting at 99.8% and a ratio of double-negative results at 0.2%. The sensitivity of cytology and hrHPV screening of different cervical cancer histologic subtypes was also demonstrated. In this large retrospective study, we systematically reported the cytology, hrHPV, pathology, and stages of cervical cancer that colposcopy-directed biopsy failed to detect.

[Value of endocervical margin examination of conization specimens. Prospective study conducted on 150 patients].

To assess the usefulness of frozen sections (FS) on endocervical margin in surgical conization or loop electrosurgical specimens. In a prospective study, 150 patients were treated from October 1995 to December 1997: 69 cases without FS, 81 cases with FS. CIN on frozen section resulted in an immediate additional resection. In the group without FS, 13 patients had involved endocervical margin by high-grade CIN (18.8%). Frozen section was impossible in a conization specimen that was too short. FS revealed 64 normal glandular epitheliums, seven squamous metaplasias in which two lesions were under-evaluated (being in fact CIN on permanent sections), eight high-grade CIN followed by additional resection in six cases and two invasive carcinomas. Endocervical margin on additionals section were always free of disease. The rate of failure was 2.6% among 77 cases. This rate corresponded to two under-evaluations. Invasive carcinoma and CIN without additional resection were excluded because frozen section only allowed a peroperative diagnosis. The average height of the cone and the rate of complications were similar. Repeat surgery was necessary in nine cases in the group without frozen section, in which five showed residual lesions, absent in the other group. The ultimate histological interpretation was never difficult after frozen section. This method permits reduction of cases with involved cone margin and residual lesions and, despite some limitations, it may be useful for surgical management.

The management of cervical intraepithelial neoplasia during pregnancy: is colposcopy necessary?

The 2006 American Society for Colposcopy and Cervical Pathology Consensus guidelines state that it is acceptable to defer colposcopy until 6 weeks postpartum in pregnant patients with atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesion (LSIL) cytology. Therefore, we sought to determine the incidence of cervical intraepithelial neoplasia (CIN) 2,3 in pregnant patients referred to a university colposcopy clinic. A retrospective study identified all pregnant women with abnormal cytology referred to the University of Alabama at Birmingham colposcopy clinic between May 2005 and September 2007. After an institutional review board approval was obtained, demographic information, referral cytology, and histologic data were collected. The colposcopic impression was also obtained from the records. Six hundred twenty-five pregnant patients were identified. The mean age was 23 years (range, 14-44 years), the mean parity was 1 (range, 0-7), and the mean gestational age was 24 weeks (range, 4-39 weeks). The most common referral cytology was LSIL (41.0%), followed by ASC-US (34.1%), and high-grade squamous intraepithelial lesion (13.6%). One hundred thirty-eight patients (22%) underwent cervical biopsy at the time of initial colposcopy. Forty-three patients had CIN 1, 28 patients had CIN 2, and 23 patients had CIN 3. Forty-four patients (32%) had no evidence of CIN on biopsy. There were no cases of invasive cervical cancer identified. Of the 469 patients with ASC-US and LSIL cytology, 20 of 78 patients who had a cervical biopsy were diagnosed with CIN 2,3. Of the 128 patients with high-grade intraepithelial lesion or high-grade squamous intraepithelial lesion cytology, 31 of 60 patients who had a cervical biopsy were diagnosed with CIN 2,3. Repeat colposcopy in the third trimester was performed on 47 patients. Only 3 of 13 patients with a repeat biopsy had CIN 2,3. Pregnant patients with ASC-US or LSIL cytology rarely have colposcopically suspected CIN 2,3 at their initial colposcopy that warrants a cervical biopsy; therefore, it is reasonable to defer the initial colposcopy in patients with ASC-US and LSIL until at least 6 weeks postpartum.

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.

Verrucous carcinoma of the cervix: detection of carcinogenetic human papillomavirus types and their role during follow-up.

Verrucous carcinoma is a rare variant of well-differentiated squamous cell carcinoma of the uterine cervix. Infection with high-risk human papillomavirus (HPV) is the main cause of intraepithelial and invasive neoplasias of the female genital tract, but the aetiology of verrucous carcinoma is still unknown. The aim of this study was to evaluate the presence of HPV in verrucous carcinomas of the cervix and to investigate the persistence and the role of high risk HPV types in follow-up. Three patients, with atypical cytologies, were observed. All the patients underwent cytology and colposcopy followed by direct biopsy. The Hybrid Capture II microplate method was used for molecular detection of pre-surgical low- and high-risk HPV types. HPV tests were performed during the follow-up, annually. The cytological findings revealed that atypical squamous cells "cannot rule out high-grade lesion" (ASC-H) in one case and high grade squamous intraepithelial lesion (H-SIL) in two cases. The HPV test detected high risk HPV types. Colposcopic findings showed cervical exophytic lesions. The histology revealed a well-differentiated verrucous carcinoma Ib stage, according to FIGO classification, in every case. Following radical hysterectomy, the post-operative course was uneventful. The mean follow-up time was 4.6 years. The follow-up HPV tests of the H-SIL patients were consistently negative as to cytological and colposcopical findings and no relapse was observed. At one-year follow-up the ASC-H patient who had shown postoperative histological features of koilocytosis associated with CIN2 and VAIN 3 had a persistence of high-risk HPV types with negative cytological and colposcopical findings. The HPV test was positive for two years and colposcopic and histological findings of VAIN degree 2 were revealed three years after surgery. Following vaginal laser CO2 vaporization the subsequently cytological and colposcopic checks were negative as was molecular detection of HPV. Follow-up colposcopy, cytology and molecular detection of HPV is recommended in all verrucous carcinoma patients since carcinogenic HPV DNA detection could represent a valuable diagnostic tool as an adjunct to cytology, for monitoring HPV infections with transforming potential.

The colposcopy and the cone biopsy in the diagnosis, treatment and follow-up of 81 cases of cervical intraepithelial neoplasia.

A conization was performed on 81 patients with histological diagnosis of cervical intraepitelial neoplasia (CIN), whom and previously a rigorous colposcopic examination. 64 patients were younger than 35 years. The previous strict colposcopic examination determined that in none of the cases were the surgical margins of the cone biopsy affected: In 26 cases there was no correlation between the previous biopsy and the histological diagnosis of the cone biopsy. The latter was--higher in degree in 9 cases and, in addition to this, in the 23 histerectomies that were performed after the conization, 7 surgical specimens showed CIN in their histological study. The non-involved surgical margins--that could be obtained in those cases with a careful previous colposcopy,--can not guarantee the exeresis of all the CIN zones. The biopsy of an atypical zone, in a colposcopic extensive lesion, cannot be representative of the whole lesion. In the follow-up--5 years maximum and 1 year minimum--3 relapses had appeared and 9 pregnancies had been diagnosed, that had not showed an increase in the number of premature labours, nor in the cesareas-rate.

Colposcopy, cytology and histology in the diagnosis of squamous intraepithelial lesions of the cervix.

To compare colposcopic findings to cytologic and histological diagnoses in women with colposcopic reports of ANTZ and/or HPV infection. Among 791 hospitalized women referred for colposcopic examination, colposcopy showed ANTZ grade 0-2 and/or HPV infection in 271 patients (34.26%). Only 153 were fully investigated by colposcopy, cytology (under colposcopic observation) and histology (target punch biopsy: 109 patients; surgical specimens of hysterectomy: 42 patients; conization: 2 patients). Cytological and histological diagnoses were reported according to the Bethesda System. 132/153 Pap smears were estimable for sampling adequacy; 44/63 resulted as normal and were histologically positive for LSIL [1]. Five LSIL-positive Pap tests were negative on histology (false negative and false positive rate of 33.33% and 3.78%). The pap test was diagnostic for intraepithelial neoplasia in 34/65 cases (53.3%) and for invasive cancer in 6/11 cases (54.5%). In 67/132 cases (50.8%) adequate-for-sampling Pap smears could not predict the exact diagnosis. On the other hand, 108/141 patients with colposcopic evidence of ANTZ/cancer showed histological SIL or invasive neoplasm (76.59%): ANTZ 1 was associated to LSIL and HSIL in 74.1% and 2.4%; ANTZ 2 to LSIL, HSIL and invasive cancer in 41%, 30.76% and 10.3%. Colposcopic suspicion of invasive cancer in 8 patients was histologically demonstrated in 7 (87.5%); colposcopic diagnosis of HPV infection was confirmed in 10/12 (83.4%). A better correspondance was shown between colposcopy and histology than between cytology and histology in the diagnosis of SIL. We suggest a routine colposcopy investigation for all patients admitted to a gynecological clinic and we believe it is very important to take Pap smears under colposcopic observation if colposcopy and cervical smears are performed in the same sitting.

Positive margins after conization and risk of persistent lesion.

The aim of this study was to investigate a method to reduce the frequency of uterine reoperation with no persistent lesion and to identify factors predictive of persistent or recurrent lesions. Of 505 conizations performed by the same surgeon, 71 had positive margins (average patient age = 35.7 +/- 7.7 years). The patients underwent either immediate reoperation or monitoring with a Pap smear and colposcopy. Histologic assessment of the cervical cone after conization showed positive margins in 14.1% of cases [endocervical and exocervical margins affected in 50 of 505 (9.9%) and 21 of 505 (4.2%) cases, respectively]. Of 59 of these patients (83.1%) who underwent follow-up monitoring over an average of 35.2 months (range: 2.6-180. 8), 12 patients (average age: 40.8 +/- 6.4 years) underwent immediate hysterectomy and 47 (average age 34.0 +/- 7.4 years) benefited from monitoring first [secondary discovery of 19 persistent lesions within 6 months and 9 recurrences within 18 months on average (range: 8.8-48 months)]. Of the 9 patients with recurrent lesions, 7 underwent reintervention and 2 monitoring. Of the 19 patients with persistent lesions, 18 underwent reintervention and 1 monitoring. Normal histology was observed in 29.4% of patients undergoing secondary reoperation for an abnormal smear compared with 66.7% of patients undergoing immediate reoperation (P = 0.04). Severity of lesion and age of patients could not be used to predict the incidence of a persistent or recurring lesion. Seventy-nine percent of conizations had positive endocervical margins in patients with a recurring or persistent lesion compared with 48% in patients with normal follow-up (P = 0.03). Cytology and colposcopy follow-up in cases of positive conization margins may help to establish justification for the choice of reoperation, thereby limiting morbidity following repeated surgery.

Treatment of carcinoma in situ: evaluation of 1609 cases.

In 1609 cases of carcinoma in situ, various methods of treatment were adopted: primary irradiation (22 cases), radical hysterectomy (11), simple hysterectomy (418), cervical amputation (83), ring biopsy with cervical curettage (63), and conization alone (1012). The outcome was related far less to the method of treatment than to the reliability of the primary diagnosis. If the latter was based only on colposcopically directed punch biopsies or cervical curettage, even with ring biopsy, 2.1% of patients died of cancer. In patients treated by hysterectomy, the vaginal approach resulted in 4 times fewer recurrences than did the abdominal approach, because of visualization of the extent of the lesions. Best results were obtained after conization with serial step-sectioning of specimens. Among 634 cases treated by conization with total removal of the lesion, there were no recurrences.

Abnormal Pap smear frequency and comparison of repeat cytological follow-up with colposcopy during patient management: the importance of pathologist's guidance in the management.

Cervical cancer contributes to a significant global health burden with room for improvement of primary prevention methods. This study aimed to determine the prevalence of Turkish women with abnormal cytology and their management by comparing results from repeat cytological analysis with close follow-up and colposcopy. A retrospective evaluation of 8738 women who underwent Pap smears at a single institution during 2011 was performed. Either repeat cytological analysis or colposcopic biopsy was used for follow-up evaluation of women who had abnormal index cytology. From the 8670 women, 8259 of had normal cytology results (95.3%) and 411 women had abnormal cytology (4.7%) in the index Pap smear. The frequency of initial abnormal cytology was 65% (n=267), 27% (n=111), 3.4% (n=14), 2.4% (n=10), 1.9% (n=8), and 0.3% (n=1) for atypical squamous cell of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), ASC cannot exclude high-grade intraepithelial lesion (ASC-H), high-grade SIL (HSIL), atypical glandular cells (AGC), and invasive cancer, respectively. Of the 267 women with initial ASCUS, 108 (40.4%) underwent repeat cytology analysis, 84 (31.5%) underwent colposcopic biopsy, and 75 (28.1%) were lost to follow-up. On histopathology, 8.3% (n=7) of patients had cervical intraepithelial neoplasm 2 (CIN2) on colposcopy. Of 60 women with LSIL that underwent colposcopic biopsy, 13.3% (n=8) had CIN2/3. The results of the study suggest that routine cytological follow-up may be an appropriate method in the management of ASCUS instead of immediate colposcopy while immediate colposcopy cannot place repeat cytology for LSIL in developing countries.

Colposcopy, conization, and hysterectomy practices: a current perspective.

Data from the provincial cytology program has shown a progressive increase in the number of cases of cervical carcinoma in situ detected in the general population and a doubling of disease rate in third decade women, with most of the cases now in the 25- to 29-year-old age group. The introduction of a colposcopy service has led to a significant decrease in the number of diagnostic conizations performed over a 5-year period. Conization was still used for therapy in a substantial number of women despite the availability of cryotherapy and laser surgery. Eighty-five percent of all patients undergoing cone biopsy had sever dysplasia or carcinoma in situ (CIN III) on pathological examination. In 25% of patients, the conization specimen revealed either dysplasia or carcinoma in situ extending to resection margins. During review of 2249 patients, 1174 were spared a conization and were treated by either hysterectomy, cryotherapy, or laser surgery. It would appear that, although colposcopy can reduce dramatically the number of diagnostic cone biopsies, conization will still be required for therapy in a substantial number of patients.

Post-hysterectomy rare collision vulva tumor with long-term human papilloma virus infection composed of squamous cell carcinoma of the labia major and adenosquamous carcinoma of bartholin gland: A case report.

Post-hysterectomy collision tumors of the vulva has rarely been reported. Though long-term HPV infection may induce vulva tumor, but the relationship between HPV infection and collision vulva tumor is not clear. And there are no clear rules of the post-hysterectomy cancer surveillance for human papilloma virus (HPV) long-term infections. So here we first report a case of post-hysterectomy rare collision vulva tumor with long-term HPV infection composed of squamous cell carcinoma of the labia major and adenosquamous carcinoma of bartholin gland and hope to bring new direction to our future research. A 48-year-old woman with long-term HPV infection, 3 years after hysterectomy, gravida 3, para 2, was admitted to our hospital with complaints of a 4-month history of an itching vulva ulceration. An anabrosis was located on the surface of the solid mass of the bartholin gland at the posterior part of the right labium and the right inguinal lymph nodes were palpable. Result of the incisional biopsy of the ulcer area at local hospital was atypical squamous cells couldn't exclude high-grade squamous intraepithelial lesion (ASC-H). Subsequently more authoritative pathological consultation results suggested squamous cell carcinoma of the vulva. Post-hysterectomy collision vulva tumor with long-term HPV infection composed of squamous cell carcinoma of the labia major and adenosquamous carcinoma of bartholin gland. The extensive excision of the vulva, bilateral inguinal lymph nodes dissection, and local skin flap transposition surgeon was done to this patient. The final certificate diagnosis was: vulvar tumor T1bM0N0 composed of squamous cell carcinoma of the labia major and adenosquamous carcinoma of bartholin gland; HPV infection; post hysterectomy, and bilateral salpingectomy. The patient recovered well after surgery, and consequently received 6 courses of TC (paclitaxel + carboplatin) chemotherapy, and 9 months and 13 days followed up. So far patient recorded as complete response (CR). Collision vulva tumor occurred post-hysterectomy is extremely rare. It is most likely related to long-term HPV infection, which suggests us should to modify the manner of the post-hysterectomy cancer surveillance for HPV long-term infections. For patients with high-risk HPV infection, even if the cytology results are negative, we may should perform colposcopy and vulva biopsy more positively to prevent the disease from progressing into cancer. And the pathogenesis of relationship between HPV infection and collision vulva tumor is still need further investigation.