Alexander Meisels

Human papillomavirus and cancer of the uterine cervix

Abstract Human papillomavirus infection of the cervix was found in 1.69% of 234,715 women during a mass screening program during the years 1975 to 1979 inclusive. Condylomata of the cervix represent the most prevalent squamous lesion diagnosed during this 5-year period. Most of condylomata (71.16%) were found in women under 30 years of age with a mean of 27.47 years and a peak incidence of 2.5% in the 20–25 year-age group. Condylomata precede invasive carcinoma by 27.45 years. The coexistence of condylomata was observed in 25.6% of dysplastic and neoplastic lesions. This association seems to shorten the mean time for malignant transformation. The epidemiologic behavior of condylomata appears similar to dysplasia which is considered a precursor of neoplasia. However, the high regression rate of condylomata (68.39%) implies that lowered immunity and other promoting or synergistic factors are necessary for malignant conversion.

Dysplasias of uterine cervix. Epidemiological aspects: Role of age at first coitus and use of oral contraceptives

Age at first coitus and use of oral contraceptives were studied in a highly homogeneous population (French Canadian) during a cytologic cervical cancer screening program. Both factors were known in 84,540 women without cervical lesions and in 2017 patients with mild and moderate dysplasia. Highly significant correlations were found between: early onset of sexual activity and occurrence of dysplasia; oral contraceptive use and occurrence of dysplasia; early age at first coitus and oral contraceptive use. When corrected for age at first coitus, there was a significant excess of dysplasias in oral contraceptive users. Dysplasia of the uterine cervix behaves epidemiologically like carcinoma in situ and invasive squamous carcinoma, that is, essentially as a venereal disease. It remains to be seen whether all dysplasias form one continuum or whether there are two morphologically similar but biologically distinct forms of dysplasia: one more frequent, regressing spontaneously, the other relatively rare, progressing to carcinoma in situ and invasive squamous carcinoma of the cervix. Cancer 40:3076‐3081, 1977.

100% rapid (partial) rescreening for quality assurance.

OBJECTIVE To compare the efficiency of two methods for routine quality assurance in gynecologic cytology: random rescreening of 10% of negative gynecologic smears and rapid rescreening of all negative gynecologic smears. STUDY DESIGN All gynecologic smears considered to be negative or benign and diagnosed between November 1, 1996, and December 31, 1997, were rescreened using the rapid, partial rescreening technique. Results were compared to those of the 10% random rescreening method. RESULTS Comparing the 10% review of negatives to the rapid rescreening in two comparable periods of three months, the former required review by the supervisor of 160 cases in order to find a true false negative. With rapid rescreening, the supervisor had to review fewer than eight cases to find a true false negative. Also, rapid rescreening found about four times more true false negatives than random 10% review. CONCLUSION Rapid rescreening of all negative gynecologic smears proved more efficient than 10% random rescreening.

Human papillomaviruses and vulvar vestibulitis

Objective To assess the relationship between human papillomavirus (HPV) infection and vulvar vestibulitis syndrome. Methods From November 1995 to December 1997, 135 women with vulvar vestibulitis were compared with 322 controls who had no evidence of vulvar vestibulitis. Human papillomavirus DNA was amplified by polymerase chain reaction and detected with liquid-capture molecular assay. Results Human papillomavirus DNA was found in 29.6% of cases and in 23.9% of controls (relative risk [RR] 1.4; 95% confidence interval [CI] .8, 2.2). The prevalence of HPV tended to decrease with increasing duration of pain among cases. Thus, prevalences were 37.5%, 29.6%, and 22.0% for pain durations of 3–6 months, 7–12 months, and 13–24 months, respectively (P = .14). Prevalence of HPV also tended to increase with pain intensity among cases, but that association was not statistically significant (P = .57). Prevalence percentages for women with low, moderate, or severe pain were 27.5%, 28.8%, and 34.4%, respectively. Prevalence of HPV was slightly higher in cases with the most severe pain (34.4%) than in controls (23.9%) (RR 1.8; 95% CI .8, 4.0). In cases with the most pain in the shortest time (3–6 months), prevalence of HPV was double that of controls (50% versus 23.9%) (RR 3.5; 95% CI 1.0, 12.7; P = .054). Conclusion There was little support for the idea that HPV might be related to vulvar vestibulitis.

Human papillomavirus and cervical lesions.

Human papillomavirus (HPV) infection has been implicated in the intraepithelial cervical changes that cause most abnormal Papanicolaou smears. To date, 14 types of HPVs have been identified. All are small, nondeveloped, icosahedral DNA viruses that share a common internal antigen. In cases of cervical HPV infection, the koilocytes and dyskeratocytes are the most frequently seen cell types. Most infections are flat aceto-white lesions. Florid condyloma acuminatum, usually detectable with the naked eye, is characterized by an irregular surface secondary to finger-like projections, in the middle of which a capillary loop comes to the surface. Spiked condyloma, not seen with the naked eye, has an irregular surface that shows asperity. 3 techniques have been used to differentiate atypical condyloma from intraepithelial neoplasia: microspectrophotometric studies, the peroxidase- antiperoxidase technique, and electronmicroscopy. There is growing evidence that papillomaviruses play an etiologic role in human genital cancer. 20-25% of dysplastic and neoplastic lesions show a coexistence of condylomas of the cervix or vulva with dysplasia or neoplasia. Epidemiologic research suggests that cervical condylomas occur at a mean age of 27.5 years, precede cervical dysplasia by 3.3 years, carcinoma in situ by 9.3 years, and invasive carcinoma by 27.4 years. The conversion of most cases of papillomas into squamous cell carcinomas requires the presence of carcinogenic initiators, 1 of which is believed to be herpes simplex virus.

VAGINAL CONDYLOMATA: A HUMAN PAPILLOMAVIRUS INFECTION

In our clinic, as a rule, we do not treat vaginal condylomata. They are usually subclinical and asymptomatic. When atypia is present on biopsy, they should be treated in the same manner as vaginal intraepithelial neoplasia. When vaginal discharge and pruritus are present, infection should be searched for and treated. When condylomata are seen with the naked eye, colposcopy has shown that there were many more, too small to be seen, so that local therapy seems a waste of time. If on colposcopic examination only a few condyloma acuminata are located, then therapy is defendable. CO2 laser therapy should be preferred to other modalities until a systemic treatment is available and safe.

Cytologic Predictors of Cervical Intraepithelial Neoplasia in Women with an ASCUS Pap Smear

OBJECTIVE To identify cytologic parameters on Pap smears of women with an atypical squamous cells of undetermined significance (ASCUS) diagnosis that could help cytologists to indicate whether a particular ASCUS case is most likely related to cervical intraepithelial neoplasia (CIN) grade 1 or 2/3. STUDY DESIGN A total of 360 eligible women diagnosed with ASCUS and referred to the colposcopy clinic of Saint-Sacrement Hospital participated in the study. Eligible women were those aged 18-50 years, newly diagnosed with ASCUS, with no history of cervical biopsies or treatment, and not pregnant at the time of the visit. Colposcopically directed biopsies of lesions were obtained. All Pap smears were reviewed according to 36 different cytomorphologic criteria. The regression logistic model was used to estimate the odds ratios (ORs) for the associations between cytologic criteria observed in smears and the diagnosis of CIN made on biopsies. All cytologic criteria significantly (P < .05) associated with CIN were entered in the models, and a backward selection was done to determine independent cytologic predictors of CIN 1 and 2/3. RESULTS Biopsies revealed that 22.2% of the study population had concurrent CIN. CIN I and 2/3 were identified in 61 (16.9%) and 19 women (5.3%), respectively. Clear perinuclear spaces (OR = 2.5, P = .002) and moderate nuclear atypia (OR = 4.4, P = .02) were two cytologic criteria independently associated with CIN 1. Four independent predictors of CIN 2/3 were identified: the presence of clear perinuclear spaces (OR = 5.9, P = .004), hyperchromasia (OR = 3.9, P = .04), moderate anisokaryosis (OR = 13.1, P = .01 and increased nuclear volume of metaplastic cells (OR = 5.1, P = .007). CONCLUSION These observations may help cytologists to better categorize ASCUS lesions as intraepithelial ones and will also contribute to improving the Bethesda definition of ASCUS. Further studies are planned to validate these observations.

Cervical condyloma planum.

Abstract Condylomata were defined and described as wart-like lesions with papillary projections often observed on the skin and mucosa of the anogenital area. Cytologic, histologic, and colposcopic studies have demonstrated that the condylomatous lesion on the cervix presents itself more frequently as a flat lesion than a classical exophytic papillary one. Condyloma planum represents a new lesion on the human cervix, not described until 1977. 1,2 The viral etiology of this new type of condyloma has been confirmed in three ways: by the electron microscopic observation of human papillomavirus (HPV) particles, 1,3–8 by the identification of viral antigen using the peroxidaseantiperoxidase technique, 9–13 and by demonstrating the presence of the HPV DNA sequences using molecular cloning and hybridization techniques. 5,14

Leopold G. Koss (1920–2012): A multi‐author tribute

I first learned of Dr. Koss during my cytotechnology training at Memorial Sloan-Kettering Cancer Center. His text was required reading and I appreciated the way he was able to make complicated topics understandable. He was a great teacher. I first met Dr. Koss when I came to work in his department in 1986 as assistant supervisor. I think he saw me initially as someone to do errands for him. As time went by, he began to see me more as an assistant, taking me with him when he gave workshops. This afforded me a glimpse of the groupies that would flock to him to have him sign their copies of his book and by extension to me with, “What’s it like working for DR. KOSS?” Having the opportunity staying late in the evenings chatting in his office listening to Mozart, afforded a more personal view of him. He was in a sense, developing into my cytology grandfather. Close, but still at a distance. Eventually, we began to collaborate. He, the master of 5 languages, would sometimes give me manuscripts to proof read and edit. I felt inadequate to the task but did my best. I doubt he appreciated my viewpoints, but it would trigger discussion of the fine points of the article. When I decided to leave in 1996, he tried to talk me into staying but understood the opportunity ahead of me. I will remember him as the kind gentleman who took me under his wing and taught me a few things about cytology and life. Rest in Peace, Dr. Koss (Fig. 1).