John Boyce

Human immunodeficiency virus infection and cervical neoplasia

To determine the relationship between human immunodeficiency virus (HIV) infection and cervical neoplasia, the characteristics of invasive and preinvasive cervical disease in 114 patients of known HIV status were assessed. Seven of thirty-seven patients (19%) under age 50 with invasive cervical carcinoma were HIV-positive, including a 16-year-old with stage IIIB disease. HIV-positive patients had more advanced invasive cancer than HIV-negative patients. Disease persisted or recurred in all HIV-positive patients compared to 37% of HIV-negative patients. In HIV-positive patients, the median times to recurrence and death were 1 and 10 months, respectively. No HIV-positive patient had HIV-related symptoms. The mean T4:T8 cell ratio in HIV-positive patients was 0.49, compared to 1.86 in HIV-negative patients. The mean T4 cell count was 362/mm3 in HIV-positive and 775/mm3 in HIV-negative patients. Colposcopic evaluations of the lower genital tract of 77 patients with abnormal smears revealed higher-grade cytology and histology in 25 HIV-positive than in 52 HIV-negative patients. HIV-positive patients had significantly more multifocal/extensive lesions, multisite involvement, perianal involvement, evidence of human papillomavirus (HPV) infection, and associated gynecologic infections than HIV-negative patients. In areas at high risk for HIV infection, we must anticipate a high prevalence of HIV seropositivity in women with invasive cervical cancer. In the HIV-infected, cervical cancer is of advanced stage and responds poorly to therapy. Intraepithelial neoplasia in HIV-positive patients may be of higher grade than in HIV-negative patients, with more extensive involvement of the lower genital tract.

Prognostic factors in stage I carcinoma of the cervix

Abstract In a series of 177 cases of Stage I epidermoid carcinoma of the cervix, 139 were treated surgically. Increasing depth of invasion of the cervical lesion was associated with greater lateral extension and increasing vascular invasion in the cervix. Increasing depth of invasion in the cervix was significantly associated with (1) increasing incidence of pelvic node metastases, (2) increasing incidence of local extension outside the cervix with negative pelvic nodes, (3) increasing frequency of recurrence, and (4) decreasing 5-year survival. Patients with extension to the corpus and negative pelvic nodes had poor survival rates. Patients with disease confined to the cervix had poor outcome if the tumor invaded more than 10 mm and was present in vascular spaces. Poor prognostic factors to consider in therapeutic planning are (1) a depth of invasion greater than 10 mm, (2) lateral spread to more than half the cervix, (3) invasion of lymph-vascular spaces in the cervix, (4) spread to the pelvic nodes, and (5) spread to the parametria or corpus uteri.

The significance of atypical vessels and neovascularization in cervical neoplasia

The relationship between atypical vessels seen colposcopically and dysplasia, carcinoma in situ (CIS), microinvasion, and frank invasion was studied quantitatively. No atypical vessels were found with dysplasia, but 2.8% of patients with CIS had atypical vessels. Half of the patients with microinvasion and all of the patients with frank invasion, in whom the entire zone of transformation was viewed, had atypical vessels. Eight-two percent of the patients with atypical vessels had invasion. The conclusions are: (1) Atypical vessels are not present with dysplasia and rarely present with CIS. (2) Atypical vessels may be associated with microinvasion, but are required for frank invasion to occur. (3) Because atypical vessels are usually associated with invasion, which can be in or near the field of atypical vessels, diagnosis cone biopsy should be performed if atypical vessels are seen and colposcopic biopsies do not show frank invasion. (4) Microinvasion without atypical vessels may be a localized disease.

The relationship between human papillomavirus and lower genital intraepithelial neoplasia in immunosuppressed women

In a group of 20 immunosuppressed women with lower genital neoplasia, evidence of associated human papillomaviral infection was found in all patients on the basis of the histologic identification of koilocytes in the upper strata of areas of mild or moderate dysplasia. Immunohistochemical study of similar areas disclosed human papilloma structural antigens in the lesions in 60%, while 50% had lesions in which human papilloma virions were detected by the electron microscope. An abnormal immunologic status, indicated by an altered T-helper/T-suppressor ratio, a deficient response to mitogenic stimulation, or both, was confirmed in 80% of the patients studied. Twelve of the 20 patients had unusually persistent and recurrent intraepithelial neoplasia, and in one the disorder progressed to invasive epidermoid carcinoma. The progressive behavior of human papillomavirus-associated neoplasia in these immunosuppressed patients might represent an accelerated version of the long-term course of such lesions in immunocompetent hosts.

Prognostic factors in carcinoma of the vulva

The clinical and pathologic characteristics of epidermoid carcinoma of the vulva in 84 women treated by vulvectomy were evaluated in relation to inguinal node status and survival. Tumor diameter, depth of invasion, clinical node status, vascular invasion, and pattern of invasion were all individually correlated with the pathologic status of the inguinal nodes. However, when evaluated in combination, only the clinical status of the inguinal nodes, the depth of invasion, and the pattern of invasion (in this order of significance) were predictive of pathologic inguinal node status. Tumor diameter, inguinal node status, depth of invasion, pattern of invasion, and vascular invasion were individually correlated with survival. When evaluated in combination, the clinical diameter of the lesion was the most important predictor of survival; depth of invasion and vascular invasion contributed additional information.

Incidence, significance, and follow-up of para-aortic lymph node metastases in late invasive carcinoma of the cervix

One hundred and four patients with Stages II and III of cervical carcinoma underwent para-aortic node biopsies. Of these, 12.5 per cent of patients with Stage IIA, 14.9 per cent of patients with Stage IIB, and 38.4 per cent of patients with Stage III carcinoma of the cervix had positive para-aortic nodes. They subsequently recieve 6,000 rads to the para-aortic area. The radiotherapy complication rate was high. Within four years, 50 per cent of the patients with positive para-aortic nodes had other distant metastases. The two- and four-year follow-up is presented. Only one of 13 patients with positive para-aortic nodes was alive at the end of four years.

Vascular invasion in stage I carcinoma of the cervix

Vascular invasion was identified as an important prognostic variable for all lesion sizes in 138 patients with Stage I cervical carcinoma. A matched pairs analysis, controlling for lesion size and extracervical spread, showed that vascular invasion was significantly associated with poor outcome. Regression analysis also indicated that vascular invasion contributed prognostic information beyond that available from lesion size and extracervical spread. Studies of adjunctive therapy based on the prognostic variables are recommended. Cancer 53:1175‐1180, 1984.

Diagnosis and management of microinvasive (stage IA) carcinoma of the uterine cervix

One hundred and sixty‐two cases of Stage IA microinvasive carcinoma of the cervix are presented. These patients represent the combined experience at the University of Miami School of Medicine, Miami, Florida, and Downstate Medical Center, Brooklyn, New York. The criteria used in both institutions are 1) penetration of invasive carcinoma beneath the basement membrane of less than 1 mm and 2) absence of invasion of blood vessel or lymphatic spaces. All tissue specimens have been measured accurately by use of calibrated optics. The literature has been reviewed for criteria of diagnosis of microinvasive cancer, as well as methods of management. Our method of accurately determining depth of penetration is described and the evolution of microinvasive cancer is presented in a series of photomicrographs in which measurements are accurate to 0.1 mm. In the literature, when depth of penetration of up to 5 mm is used as criterion for microinvasive carcinoma, the incidence of nodal metastasis may be as high as 3.5%. Since, in our combined institutions, the mortality rate with radical hysterectomy is less than 1% and the incidence of ureterovaginal fistulas is 1.2%, we conclude that simple hysterectomy is not adequate therapy for lesions with stromal invasion to a depth of 5 mm.

Missed opportunities for early diagnosis of cancer of the cervix.

In a low-income community, 52% of new invasive cancer of the cervix arose in women who had no previous Pap smear, while 62% arose in women with no smear within five years. In the previous five years, 73% of the unscreened women had received ambulatory medical care (including 41% who had regular care for chronic conditions), while 16% were hospitalized. Much of the unscreened low-income population could be reached by routine screening in regular ambulatory health services and hospitals.

Prognostic factors in cervical carcinoma: implications in staging and management

Individualization of treatment using judicious combinations of external and intracavitary irradiation remains the cornerstone of the radiation management of carcinoma of the cervix. The inherent propensity of this cancer to either confine itself to the pelvis or else spread in a systematic and predictable manner through lymphatic channels has facilitated its therapeutic control. The treatment of most early invasive cervical carcinomas is equally advantageous using either intracavitary radium or surgery. However, certain Stage I patients have morphologic and histologic characteristics that militate against tumor control. Factors such as tumor size, depth of invasion, vascular infiltration, uterine extension, and barrel‐shaped presentation affect the course of the disease and survival. A clinical‐pathologic staging for cervical carcinoma incorporating the above mentioned factors into the current clinical FIGO staging system has been suggested. It aims to facilitate the recognition of those early tumors that require additional external radiotherapy. A description of the role of surgery, intracavitary and external radiation, and their combinations is included. In advanced carcinoma of the cervix, failure can be attributed to either large tumors containing cores of hypoxic cells resistant to conventional radiation therapy or to uncontrolled subclinical disease in the lymphatics at or near the border of the irradiated area. Radiotherapy combined with surgery, oxygen enhancers, infusion chemotherapy, and large particle high LET radiation has been implemented to increase local control; for distal failures, extended field irradiation of paraaortic nodes has been found to be technically feasible and well tolerated and is being studied for its effects on increased survival. The rationale for newer treatment procedures, including preliminary results and their complications, is discussed.