Hsil and Cervical Carcinoma in Ascus Cervical Cytology

To determine the prevalence and factors associated with histologic diagnoses of High Grade Squamous Intraepithelial Lesions (HSIL) or invasive cervical cancer in women with a cytologic diagnosis of atypical squamous cells of undertermined significance (ASCUS), medical records of women with an ASCUS Pap smear from January 2003 to December 2006 were reviewed. Of 287 women with ASCUS Pap smears in whom data were available, 189 were annotated with “favoring a premalignant or malignant process”, 74 with “favoring reactive”, and 24 with “not otherwise specified”. The prevalences of HSIL and invasive cervical cancer were 9.1% and 1.2%, respectively. Only subtypes of ASCUS were significantly associated with the detection of HSIL or invasive cancer, 12.7% with favoring premalignant or malignant process, 2.7% with favoring reactive, and 16.7% in with ASCUS-NOS (p=0.034). cervical cytologic screening programs. The first system to detect and report cervical cytology was the Papanicolaou system which was developed in 1943 and has been used for many years (Papanicolaou and Traut, 1943). However, with emerging knowledge about human papilloma virus (HPV) as an important etiologic agent in cervical cancer, a new cytologic classification, the Bethesda System, was adopted in 1988 (National Cancer Institute Workshop, 1989). In the Bethesda classification, cervical intraepithelial neoplasia (CIN) was replaced by squamous intraepithelial lesion (SIL). A detection of HPV virus has been included in this new classification and is classified together with CIN I as a low grade SIL (LSIL) while CIN II and III were classified as high grade SIL (HSIL). Any cellular atypia which is more marked than those attributable to reactive changes but quantitatively and qualitatively falls short of a definitive diagnosis of SIL INTRODUCTION Cervical cancer is the second most common gynecologic cancer worldwide, accounting for 15% of all female cancers in developing countries (Parkin et al, 2002). In Thailand, cervical cancer is the most common gynecologic cancer, found in 20.9 in 100,000 women and is also the most common cause of death (Srivatanakul et al, 1999). One effective means to reduce mortality from cancer of the cervix is early detection and treatment of pre-invasive cervical lesions. This can be achieved by SOUTHEAST ASIAN J TROP MED PUBLIC HEALTH 738 Vol 39 No. 4 July 2008 is termed as “atypical squamous cells of undetermined significance” (ASCUS). Because of the uncertain denotation of ASCUS, this term was further subcategorized in the 1991 Bethesda system (National Cancer Institute Workshop, 1993) into “reactive change”, “premalignant/malignant” or truly “not otherwise specified”. In the 2001 Bethesda system, “atypical squamous cell” (ASC) was changed (Stoler, 2002) to “atypical squamous cells of undetermined significance” (ASCUS) and “atypical squamous cells those can not exclude high grade squamous intraepithelial lesion (ASC-H)” according to the interpreting cytopathologist. As a quality assurance not to overuse this term, the rate of ASCUS reported at any institution should be kept within the range of 35% (Davey et al, 2000; Stoler and Schiffman, 2001). However, the rates reported by many studies vary from 3.6-23.5% (Lindheim and Smith-Nguyen, 1990; Abu-Jawdeh and Wang, 1994; Auger et al, 1997; Williams et al, 1997; Kinney et al, 1998; Lachman and CavalloCalvanese, 1998; Dvorak et al , 1999; Lousuebsakul et al, 2000; Massad et al, 2001; Mood and Haratian, 2004; Ghaemmaghami et al, 2005). In harmony with the wide range of prevalence rates, final diagnoses of cervical histopathology with ASCUS may vary from normal histology at one end to HSIL or invasive cancer at the other end. Because of this, options for the management of ASCUS have been proposed: follow-up under close surveillance, HPV testing, or immediate colposcopic examination to obtain cervical biopsy for histopathologic examination. A physician taking care of a woman with ASCUS cytology may choose any of the three options depending on his experience, desire of the woman, the hospital setting and equipment. However, due to the wide range of histopathology with ASCUS, it is unclear what would be appropriate follow-up for a woman who may have a risk for HSIL or invasive cancer or simply normal cervical histology, should it include expensive HPV testing, or a colposcopic examination (which may not be readily available). Having more data regarding the final outcomes of ASCUS would be useful. The purpose of this study was to determine the prevalence of the histologic diagnosis of HSIL, microinvasive or invasive cervical cancer in woman with ASCUS cervical Pap smear and to study factors which may be associated with the histopathologic diagnosis of HSIL or invasive cervical cancer (≥ HSIL) with ASCUS cytology. MATERIALS AND METHODS This study was conducted after approval by an ethics committee. Patients with a cervical cytologic diagnosis of ASCUS between January 2003 and December 2006 were identified from the archives of the Department of Obstetrics and Gynecology, Bangkok Metropolitan Administration Medical College and Vajira Hospital. The inclusion criteria were: a woman with ASCUS cytology from a conventional Pap smear performed at our institution who subsequently underwent colposcopic examination. Women with ASCUS cytology who had histology examination after fractional curettage or hysterectomy for any other coincidental pathology were also included. Women who had a history of cervical cancer or pre-invasive cervical lesions, had a prior hysterectomy, or had an incomplete medical record were excluded. The cl inical practice guideline for a woman with ASCUS cytology at Bangkok Metropolitan Administration Medical College and Vajira Hospital is to perform colposcopic examination, which is conducted by gynecologic oncologists or those in fellowship training. Tissue from colposcopic directed biopsies was obtained from any suspicious lesions. In any cases where colposcopy was unsatisfactory or where there was no gross cervical abnormality had endocervical curettage carHSIL AND CERVICAL CARCINOMA IN ASCUS CERVICAL CYTOLOGY Vol 39 No. 4 July 2008 739 ried out. Women who had satisfactory colposcopy with no suspicious lesions over ecto and endo-cervices were defined as “normal” and underwent a follow-up Pap smear. When histologic tissue biopsy revealed a lesion worse than HSIL had cervical conization by loop electrosurgical excision procedure (LEEP) or cold knife conization. Patient clinical and pathological data were retrieved from the in-patient/out-patient charts and the archives of the Anatomical Pathology Department. Data were collected regarding age, menopausal status, marital status, parity, specific subtype of ASCUS, and the definite cervical histology. Histopathology referred to the most severe histologic diagnosis at biopsy, curettage, LEEP, or hysterectomy. Data were analyzed by parametric and nonparametric statistics, using SPSS 11.5 (Chicago, IL). Descriptive statistics were used for demographic data and summarized as frequencies, percentages, means with standard deviation (SD) and medians with ranges. Differences between variables were evaluated with the chisquare test for variables that were normally distributed and the Mann-Whitney U test for variables that were not normally distributed. The primary outcome was considered significant only if the p-value ≤ 0.05.