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PubMed2004

Differences in hymenal morphology between adolescent girls with and without a history of consensual sexual intercourse.

OBJECTIVE: To compare the morphology of the hymen in adolescent girls who have and have not had sexual intercourse involving penile-vaginal penetration. SUBJECTS: Female patients aged 13 to 19 years, recruited from an urban adolescent medicine practice. METHODS: Subjects were interviewed in private after completing detailed questionnaires and then underwent a physical examination. External genital inspections were performed using a colposcope with an attached 35-mm camera to document the appearance of the hymen. The presence of notches or clefts was recorded during the examination, and photographs taken at x10 magnification were used to take measurements of the width of the posterior hymenal rim. RESULTS: Posterior hymenal notches and clefts were more common among girls admitting past intercourse (13/27 [48%]) than in girls who denied intercourse (2/58 [3%]; P =.001), but the mean width of the posterior hymenal rim was not significantly different between the 2 groups (2.5 mm vs 3.0 mm; P =.11). Two subjects who denied intercourse but had posterior hymenal clefts described a painful first experience with tampon insertion. CONCLUSIONS: Deep notches or complete clefts in the posterior rim of the hymen were rare in girls who denied intercourse. Subjects who admitted past intercourse still had nondisrupted, intact hymens in 52% of cases.

Adolescent↗
PubMed1996

Genital findings in adolescent girls referred for suspected sexual abuse.

BACKGROUND: Sexual abuse is a common problem affecting adolescent girls, but the frequency of medical findings in this population has not been specifically described. OBJECTIVE: To describe the frequency of specific genital findings in a group of pubertal girls who had experienced probable or definite sexual abuse. DESIGN: Patient series, medical chart and photograph review. SETTING: Specialty referral clinic for abused children. PATIENTS AND SELECTION: Referred sample of female patients, examined between January 1, 1987, and June 30, 1994, with Tanner genital stages 3, 4, or 5, who reported a history of penile-vaginal penetration, had colposcopic photographs taken, and were determined, by means of a previously described classification system, to have experienced probable or definite abuse. INTERVENTIONS: None. MAIN RESULTS: The study included 204 girls, aged 9 to 17 years (mean, 13 years); race or ethnicity was Mexican American in 57%, white in 34%, and other in 9%. Abnormal genital findings were documented in 32% of patients overall but were more common when the girls had reported bleeding at the time of the assault (50% vs 26%; P = .004, chi 2 analysis), or when the examination occurred within 72 hours of the last episode of abuse (69% vs 26%; P < .001, chi 2 analysis). Transections of the hymen were unusual (8%), but notches in the hymen were more common (25%). CONCLUSIONS: Normal or nonspecific results of genital examinations are commonly found in adolescents who have been sexually abused, unless the abuse was very recent. Further studies are needed to document the healing of genital injuries in victims of acute assault and the frequency of hymenal findings in nonabused, non-sexually active adolescents.

Adolescent↗
PubMed1997

Clinician agreement on physical findings in child sexual abuse cases.

OBJECTIVE: To measure agreement among experienced clinicians regarding the interpretation of physical findings in child sexual abuse cases and to determine whether knowledge of clinical history affects the interpretation of the physical findings. DESIGN: Experienced clinicians rated colposcopic photographs on a scale of 1 to 5 with 1 being normal and 5 being clear evidence of penetrating injury. To answer an additional study question of whether clinical history affected interpretation, 4 clinicians rated 69 cases in which they were blinded to the patients' histories and 70 cases in which the patients' histories were available. The other 3 clinicians then rated the same cases with the presence or absence of history reversed. SETTING: All clinicians involved perform child sexual abuse examinations at tertiary care centers. PATIENTS: A total of 139 girls with Tanner stage 1 or 2 genitalia who were referred to a general pediatric clinic at an academic medical center for examination of possible sexual abuse. RESULTS: Half of the photographs were interpreted as indicating little or no evidence of abuse. Of those photographic sets that both readers could interpret, 39% were in perfect agreement and 77% disagreed by 1 category or less. Perfect agreement across all possible pairs of readers was 34.5%. Agreement was better when the patient's clinical history was unknown (29.3% vs 38.9%, P = .005). The kappa, a measure of interrater reliability, indicated poor agreement among clinicians. The combined kappa for the first group of clinicians was 0.22 without knowledge of clinical history and 0.11 with knowledge of clinical history. For the second group of clinicians, the kappa was 0.31 without knowledge of clinical history and 0.15 with knowledge of clinical history. The overall kappa across all 7 clinicians disregarding clinical history was 0.20. Agreement was best for categories 1 (normal, kappa = 0.28) and 5 (clear evidence of a penetrating injury, kappa = 0.39). CONCLUSIONS: Clinicians educated and experienced in assessing child sexual abuse do not agree perfectly on the interpretation of photographs of genital findings in girls with Tanner stage 1 or 2 genitalia. Clinicians agree less when a patient's clinical history is available. Efforts should be directed at standardizing physical findings and avoiding overemphasis on physical findings in child sexual abuse cases.

Child↗
PubMed2002

2001 Consensus Guidelines for the management of women with cervical cytological abnormalities.

OBJECTIVE: To provide evidence-based consensus guidelines for the management of women with cervical cytological abnormalities and cervical cancer precursors. PARTICIPANTS: A panel of 121 experts in the diagnosis and management of cervical cancer precursors, including representatives from 29 professional organizations, federal agencies, and national and international health organizations, were invited to participate in a consensus conference sponsored by the American Society for Colposcopy and Cervical Pathology (ASCCP). EVIDENCE AND CONSENSUS PROCESS: Guidelines for the management of women with cervical cytological abnormalities were developed through a multistep process. Starting 6 months before the conference, working groups developed draft management guidelines based on formal literature reviews of English-language articles published in 1988-2001, as well as input from the professional community at large, obtained using interactive Internet-based bulletin boards. On September 6-8, 2001, the ASCCP Consensus Conference was held in Bethesda, Md. Guidelines with supporting evidence were presented and underwent discussion, revision, and voting. CONCLUSIONS: Management of women with atypical squamous cells (ASC) depends on whether the Papanicolaou test is subcategorized as of undetermined significance (ASC-US) or as cannot exclude high-grade squamous intraepithelial lesion (HSIL) (ASC-H). Women with ASC-US should be managed using a program of 2 repeat cytology tests, immediate colposcopy, or DNA testing for high-risk types of human papillomavirus (HPV). Testing for HPV DNA is the preferred approach when liquid-based cytology is used for screening. In most instances, women with ASC-H, low-grade squamous intraepithelial lesion, HSIL, and atypical glandular cells should be referred for immediate colposcopic evaluation.

Adolescent↗
PubMed1999

Cervical fluorescence of normal women.

BACKGROUND AND OBJECTIVE: Cervical tissue fluorescence spectra have previously been measured in vivo in women with a recent abnormal Papanicolaou smear. Diagnostic algorithms have been developed to diagnose squamous intraepithelial lesions (SILs) based on these fluorescence emission spectra. However, algorithms have not been tested in women with no history of cervical neoplasia. STUDY DESIGN/MATERIALS AND METHODS: Cervical fluorescence was measured from 54 women with no history of cervical dysplasia, and the spectra were compared to those from colposcopically normal sites in women with suspected dysplasia. Representative spectra from each group were compared and a two-sided, unpaired Student's t-test was performed to compare mean principal component scores used in previously published diagnostic algorithms. The ability of previously reported diagnostic algorithms to classify these samples as normal tissue was also assessed. RESULTS: At the 0.05 level of significance, the mean scores of 4 of the 7 important principal components were statistically different for the two populations. However, when the data collected from volunteers in this study were preprocessed in the appropriate manner and the algorithms were applied, more normal samples were correctly classified than in the previous clinical study in which these algorithms were developed. CONCLUSION: Previously reported algorithms can accurately classify tissue type based on spectra from women with and without a history of cervical neoplasia.

Adolescent↗
PubMed1996

PCR-based high-risk HPV test in cervical cancer screening gives objective risk assessment of women with cytomorphologically normal cervical smears.

Cervical-cancer screening programmes using cytomorphological criteria could be more efficient if the screening included objective individual risk factors for women with normal cytology, such as a test for high-risk human papillomavirus (HPV). The value of a PCR-based test for high-risk HPV types was studied in a cohort of 1622 women presenting in a routine triannual population-based screening programme. Women were included in the study when they had no previous history of cervical dysplasia; and their initial Pap smear was read as normal (Pap 1 or 2). The mean age of the women was 42 years (range 34-54 years) and mean follow-up time was 40 months (range 5-73 months). Women were referred for colposcopically directed biopsies if they had had 2 successive cervical smears read as Pap 3a (mild to moderate dyskaryosis) or one read as > or = Pap 3b (severe dyskaryosis). Women with histologically confirmed cervical intraepithelial neoplasia grade III (CIN III) were considered positive cases. All women were tested for 14 high-risk HPV genotypes. Of the 86 high-risk HPV-positive women, 6 developed CIN III, whereas only 1 of the 1536 HPV-negative women did. The women with normal Pap smears containing high-risk HPV genotypes were 116 times (95% CI, 13-990) more at risk of developing CIN III, in contrast to women without high-risk HPV. These results support the view that the interval between successive smears in cervical-cancer screening can be increased considerably for women with cytomorphologically normal and high-risk HPV-negative cervical smears as determined by PCR.

Adult↗
PubMed1997

Human papillomavirus (HPV) in an Icelandic population: the role of HPV DNA testing based on hybrid capture and PCR assays among women with screen-detected abnormal Pap smears.

This study was based on 358 cases with abnormal smears referred for colposcopy and HPV DNA testing. We analysed: 1) the frequency of different grades of cyto- and histopathologic findings; 2) the frequency and relative amount of HPV DNA with the hybrid capture assay (HCA) in swabs, and the frequency of HPV with PCR in swabs (-S) and biopsies (-B); and 3) the frequency of HPV types according to the grade of the cyto- and histopathologic findings. Of all cases, 95% were positive with all HPV tests combined. The HCA (HPV: 16, 18, 31, 33, 35, 45, 51, 52 and 56) and the PCR-S and PCR-B (HPV: 16, 18, 31, 33 and 35) tests for high-risk HPV exhibited sensitivities of 57%, 56% and 48%, respectively. The high-grade smears and the high-risk PCR-S HPV had about 80% sensitivity for histologic high-grade lesions compared with around 70% for HCA and the PCR-B. Combining the high-grade smears and the high-risk HPV increased the sensitivity to 93-96%. Among the cervical intraepithelial neoplasia I (CIN I) and the atypical squamous cells of undetermined significance (ASCUS) smears the sensitivity of high-risk HPV for high-grade histologic lesions was 63% for the HCA and 79% for the PCR-S. No correlation was found between the relative amount of HPV DNA detected by HCA and the grade of cyto- and histological lesions. We conclude that the results strongly indicate that HCA is less sensitive than PCR in the diagnosis of high-risk HPV, that swabs are more sensitive than biopsies as a sampling method, that high-risk HPV and high-grade smears are complementary for the diagnosis of high-grade histologic lesions and that the present role of HPV testing in screening could be limited to identifying women with low-grade smears and koilocytotic or low-grade colposcopic biopsies that are at risk of concealing or developing high-grade histologic lesions.

Biopsy↗
PubMed1997

Atypical squamous cells of undetermined significance: correlative histologic and follow-up studies from an academic medical center.

The diagnosis of ASCUS (atypical squamous cells of undetermined significance) was introduced in the 1988 Bethesda System for reporting cervical/vaginal cytologic findings. Outcome and appropriate management of patients with this diagnosis is not presently established. Criteria defining ASCUS are nuclear enlargement (2.5-3.0 times normal intermediate cell nucleus), mild nuclear hyperchromasia, smooth nuclear outlines with mild variation in nuclear size and shape, or else two, but not all three, cytologic criteria for human papilloma virus (HPV) cytopathic effect. All 668 cases reported as ASCUS from February 1992-December 1993 from our cytology laboratory were reviewed. These ASCUS cases represented 4.5% of all gynecologic cases diagnosed in that same time period. Of these, 284 (41%) had a subsequent colposcopic biopsy and/or endocervical curettage. The biopsied cases included 101 (36%) with condylomata, 38 (13%) with cervical intraepithelial neoplasia (CIN) I, 17 (6%) with CIN II, and 9 (3%) with CIN III. No cases of carcinoma were detected. Of patients with a cytologic diagnosis of ASCUS and subsequent cervical biopsy, 49% had low-grade cervical intraepithelial neoplasia (LGSIL), either condyloma or CIN I. Nine percent had high-grade cervical intraepithelial neoplasia, either CIN II or CIN III. These findings indicate that ASCUS defines cytologically a group of patients who may have either a concurrent or subsequent development of a squamous intraepithelial lesion (SIL). This forms a high-risk group. The management of cases with a cytologic diagnosis of ASCUS should be at least as aggressive as that of LGSIL.

Adolescent↗
PubMed1999

Biological behavior and etiology of inflammatory cervical smears.

Two hundred and fifty-seven consecutive women attending a major maternal and child health (MCH) center were studied clinically, colposcopically, cytologically, and microbiologically for different gynecologic infections. Out of 257 cases, 207 (80.5%) had inflammatory cervical smears, of which 183 (88.4%) were infected with one or more genital tract infections. Bacterial vaginosis (risk, 22.6-fold), chlamydia (risk, 21.6-fold), and human papillomavirus (HPV) (risk, 13.5-fold) were independently associated with inflammatory smears. In addition, significantly higher proportions of women with inflammatory smears had cervical ectopies (28.5% vs. 10.2%) and bleeding ectopies (30.9% vs. 4.1%) as compared to noninflammatory smears. Women infected with bacterial/parasitic genital infections were given specific treatment. These women were followed up at regular intervals to assess the efficacy of antimicrobial therapy. During follow-up examination, only 26 women (12.6%) showed negative smears. Sixteen women developed squamous intraepithelial lesions (SIL) during follow-up, and 163 women had persistent inflammatory smears. Multivariate analysis revealed that persistent inflammatory smears were associated with herpes simplex virus (HSV) infection, as revealed through detection of IgA antibodies to HSV (risk, 11.5-fold). Progression of SIL was associated with HPV infection (risk, 17.6 fold). Thus, inflammatory smears are associated with different types of infection, most of which do not respond to antimicrobial therapy.

Colposcopy↗
PubMed1999

Atypical squamous cells of undetermined significance: A cytohistological study in a colposcopy clinic.

Cytohistologic correlation was performed by 3 observers on 100 atypical squamous cells of undetermined significance (ASCUS) cases from a colposcopy clinic. Our objectives were to: 1) subclassify ASCUS cases and determine their clinical significance; 2) assess the independent predictive value of different cytologic parameters for biopsy-proven dysplasia (BPD); and 3) calculate interobserver variability. The prevalence of BPD was 73% in the ASCUS favor dysplasia (AFD) group, and 27% in the ASCUS favor reactive (AFR) group (P 0.001). The sensitivity of cervical cytology (AFD) for detecting BPD was 88.5%. Using multiple logistic regression, only nuclear membrane irregularity was found to be independently predictive of BPD (P 0.0001). The interobserver agreement (kappa) was 0.41. Colposcopic smears were inferior to referring smears in detecting dysplasia, with 67% of patients having a referring diagnosis of dysplasia. In a colposcopy clinic population there is a high prevalence (73%) of BPD in the AFD group. Attention should be paid to nuclear membrane irregularity in the risk stratification of ASCUS cases. Diagn. Cytopathol. 1999;21:211-216.

Biopsy↗
PubMed1999

A randomized, double-blind, placebo-controlled trial of 5-fluorouracil for the treatment of cervicovaginal human papillomavirus.

OBJECTIVE: To compare intravaginal 5-fluorouracil (5-FU) and placebo for the treatment of cervical and/or vaginal human papillomavirus (HPV). METHODS: A randomized, placebo-controlled trial was performed. Women with HPV detected visually or by Papanicolaou (Pap) test and confirmed by colposcopic biopsy were randomized to receive either intravaginal 5-FU cream or an intravaginal placebo cream. Women with cervical or vaginal intraepithelial neoplasia were excluded. The primary outcome measure was cytologic regression of HPV as determined by Pap test screening 4 to 6 months after treatment. The secondary outcome was cytologic evidence of disease progression at both the 4-6-month and 12-month follow-up evaluations. Data were analyzed using the Chi square test with significance established at P < 0.05. RESULTS: A total of forty patients were randomized, and thirty patients had a follow-up Pap test 4 to 6 months after treatment. Of those patients treated with 5-FU, 28% demonstrated regression of HPV on cytologic evaluation, compared with 69% of those treated with placebo (P < 0.05). Twelve-month follow-up cytology was available from 18 of the study participants. There were no significant differences in the frequency of cytologic progression or regression between groups at 12 months. CONCLUSION: Four to six months post treatment, the use of intravaginal 5-FU for the treatment of cervical or vaginal HPV is associated with a lower rate of regression than the use of placebo.

Administration, Intravaginal↗
PubMed1976

Histopathologic spectrum of vaginal adenosis and related changes in stilbestrol-exposed females.

A total of 98 colposcopically directed biopsies were obtained from the vagina, cervix, and cervicovaginal ridge (hood) of 80 young women believed to have had intrauterine exposure to stilbestrol (DES). Specific investigation of the patient's medical records corroborated the history of maternal stilbestrol administration in 36 patients (45%), while in the remainder the drug history was regarded as presumptive since medical records were unavailable for review. The findings did not differ significantly in those biopsies taken from patients with confirmed or presumptive drug histories. Histologic evidence of vaginal adenosis was detected in vaginal biopsies from 43 patients. In 30 cases (70%) benign Müllerian-type glandular epithelium was in the superficial vaginal wall, residing on the mucosal surface and/or in the lamina propria. The glandular epithelium predominantly was of endocervical type, but in six instances it resembled endometrial or fallopian tubal epithelium. The glands were accompanied by varying degrees of squamous metaplasia in 22 cases. When extensive the metaplasia produced transformation zones similar to those seen in the normal cervix. Vaginal biopsies of adenosis from the other 13 patients (30%) revealed squamous metaplasia without demonstrable glands due to complete transformation of all antecedent glandular epithelium by squamous metaplasia. Our studies indicate that squamous metaplasia is a component of major importance in the natural history of adenosis and that the concept of adenosis should be broadened to include those examples comprised exclusively of metaplastic epithelium. In such examples metaplasia is identified by the immaturity and poor glycogenation of the squamous cells and their accompanying squamous pegs which often contain residual gland openings or squamous "eddies." Similar findings were present in biopsies of seven cervicovaginal ridges and in cervical biopsies from 37 patients, except for the absence of endometrial or tubal type glands in the latter site. Although no adenocarcinomas were detected, six patients had squamous dysplasia of the vagina and/or cervix. In no case were premalignant or dysplastic changes of glandular cells found. Our findings support the thesis that stilbestrol-associated adenosis represents anomalous embryologic localization of the original squamocolumnar junction in the vagina rather than in the cervix. It is closely related to so-called cervical "erosions." The development of squamous metaplasia accounts for modifications in the clinical and histologic appearances by producing transformation zones which then may be subject to the same oncogenic stimuli for squamous neoplasia as are their counterparts in the cervix.

Adolescent↗
PubMed1976

Colposcopy.

The main clinical value of colposcopy in modern gynecology is in the clinical diagnosis of patients with abnormal cytology. In colposcopically directed biopsies it is possible for an experienced colposcopist to sample with a high degree of accuracy the most advanced histopathologic changes. This significantly decreases the frequency of diagnostic conization. Colposcopy can efficiently select patients for outpatient treatment of cervical intraepithelial neoplasia, since it precisely defines the size and localization of epithelial changes. A new application of colposcopy is in the evaluation of young girls who have been exposed to stilbestrol in utero. In these patients colposcopy can improve the diagnosis of changes in cervical-vaginal epithelium.

Adenocarcinoma↗
PubMed1976

Cryosurgery. Its use for the abnormal Pap smear.

During a two-and-one-half year period, 317 women were seen in the Colposcopy Clinic for evaluation of an abnormal Pap smear. Seventy-four (23%) desired to maintain their childbearing potential and were treated conservatively. Ten (14%) had inadequate colposcopy and underwent cold knife conization of the cervx. The remaining 64 were treated by adequate colposcopy, combined with cryosurgery; they are discussed in detail. All were managed economically as outpatients without anesthesia and no serious complications occurred. To date, only four have recurrent abnormal cervical cytology and several have delivered children. Adequate colposcopic examination combined with biopsies must proceed all cryosurgical procedures performed for abnormal cervical cytology.

Adolescent↗
PubMed1979

Adenocarcinoma in situ of the vagina: a case report.

The clinical and pathological features of a case of adenocarcinoma in situ of the vagina diagnosed in a 40-year-old woman with a negative history for intrauterine DES exposure are reported. The lesion was diagnosed 15 months following hysterectomy for in situ squamous cell and in situ adenocarcinoma of the cervix. The vaginal lesion closely resembled colposcopically, cytologically, and histologically previously described cases of cervical adenocarcinoma in situ. The case was of additional interest pathologically because of a focal signet-ring cell component which exhibited extensive pagetoid invasion of the adjacent squamous mucosa. No previously reported examples of vaginal adenocarcinoma in situ could be found. The histogenesis of this entity is briefly discussed.

Adenocarcinoma↗
PubMed1981

The abnormal Pap smear--what to do next?

The patient with an abnormal Papanicolaou smear must have proper and adequate diagnostic evaluation to determine the degree of cervical abnormality. Gross clinical evaluation alone is inadequate for definitive diagnosis because cytologic screening identifies patients with preclinical disease. Outpatient diagnostic evaluation must include colposcopy, colposcopic-directed biopsies, endocervical curettage, and pelvic examination. Conization of the cervix is required whenever these techniques are unsatisfactory or are unable to rule out invasive cancer. When outpatient diagnostic procedures including cytologic analysis rule out invasive disease, one may elect cryosurgery, electrocautery, or laser in treating cervical intraepithelial neoplasia. Nevertheless, conization or hysterectomy may be inpatient treatments for selected patients.

Adult↗
PubMed1983

Atypical immature metaplasia (AIM). A subset of human papilloma virus infection of the cervix.

Atypical immature squamous metaplasia (AIM) is a poorly understood lesion with uncertain biological and clinical significance. This report reviews 170 cases of cervical condylomata and 60 cases of high-grade cervical intraepithelial neoplasia (CIN II/III); AIM was found in association with 34% of condylomata and 16% of high-grade CIN. Thirty-seven cases of AIM alone were reviewed and nearly all presented with a cytologic diagnosis of CIN I or condyloma and a colposcopic appearance of white epithelium with or without punctation and mosaic structure. The mean ages of patients with condylomata, AIM, CIN II, and CIN III were 27, 27, 32, and 37 years, respectively. By immunoperoxidase techniques 75% of condylomata, 16% of AIM, and 0% of CIN lesions were positive. The histologic criteria for the diagnosis of AIM and it's morphologic distinction from CIN and relationship to condylomata, are outlined. AIM is a distinct histologic entity that shares similar epidemiologic, morphologic and biologic characteristics with condyloma. When AIM is found alone in biopsy material, careful correlation of cytology, and biopsy results should be performed and therapy should be based on the size and distribution of the lesion.

Adult↗
PubMed1984

Genital warts and cervical cancer. III. Subclinical papillomaviral infection and cervical neoplasia are linked by a spectrum of continuous morphologic and biologic change.

Human papillomaviral (HPV) infection is now widely advanced as an important etiologic factor in cervical cancer. This study was undertaken to clarify morphologic relationships within the biologic spectrum linking subclinical papillomaviral infection (SPI) to cervical intraepithelial (CIN). Two pathologists analyzed 72 colposcopic biopsies, using a semi-objective rating scheme that scored 24 different histologic criteria. Each individual criterion was checked for reproducibility, and validated against an objective measure of papillomaviral infection (immunoperoxidase staining) or premalignant change (microspectrophotometry). The individual criteria were then combined into histologic indices of benign warty change, presumed viral atypia, abnormal cell phenotype, and disturbed tissue maturation. Histologic expression of papillomaviral infection decreased with increasing degrees of premalignant change. Plotting the index of abnormal cell phenotype against that of disturbed tissue maturation produced a linear plot in which cases clustered into four diagnostic groups. The histologic indices of papillomaviral infection displayed significant curvilinear correlations with genotypic distortion, benign warty change being maximal in the CIN 1 range and presumed viral atypia in the CIN 2 range. Disturbance of nuclear DNA content also increased with worsening diagnosis; diploidy being most common in SPI (67%), polyploidy in CIN 1 (59%), and aneuploidy in CIN 2 (65%) and CIN 3 (82%). Conversely, capsid antigen production decreased from 36% in SPI to 9% in CIN 3. Three aneuploid epithelia were immunoperoxidase positive. These inverse relationships between late viral expression and nuclear distortion fit experimental models of viral oncogenesis. The gradual transition and morphologic overlap between diagnostic groups support the postulate that SPI and CIN are a single disease spectrum, in which differences are those of degree rather than of kind.

Adolescent↗