Kenneth D. Hatch

Incidence, Prevalence, and Clearance of Type-Specific Human Papillomavirus Infections: The Young Women’s Health Study

The natural history of type-specific human papillomavirus (HPV) infections was examined in a cohort of 331 women aged 18-35 years who self-referred for routine gynecological care. Participants underwent a gynecological examination at baseline and at approximately 4 and approximately 10 months after baseline. Cervical samples were collected for HPV testing and genotyping at each visit, as was information on reproductive, sexual, and medical histories. The rate of new HPV infections was 2.9% per month; the highest rates were observed for HPV types 16, 39, 84, and 51. Among women who tested negative for HPV at baseline, the cumulative probability of acquiring an oncogenic HPV strain during a 12-month follow-up period was 0.32, compared with 0.18 for nononcogenic strains. Women who had had >/=1 new male sex partner in the recent past were significantly more likely to acquire a new HPV infection (relative hazard, 2.39; 95% confidence interval, 1.20-4.76). The median time to clearance of infection was significantly longer for oncogenic strains (9.8 months) than for nononcogenic strains (4.3 months).

Responsiveness of patients with advanced ovarian carcinoma to tamoxifen. A gynecologic oncology group study of second‐line therapy in 105 patients

One hundred five patients with Stage III or IV epithelial ovarian cancer whose disease had persisted or recurred after primary surgery and first‐line chemotherapy were given tamoxifen (20 mg orally twice daily) and evaluated for response. Eighteen percent of the patients responded: 10% demonstrated a complete response (CR) and 8% showed a partial response (PR). Thirty‐eight percent of the patients had short‐term disease stabilization. CR had a median duration of 7.5 months, with the longest lasting 17 months. For patients with PR or stable disease, the median duration of response was 3 months (maximum duration, 9 months). When estrogen receptors of tumor tissue from patients demonstrating CR were evaluated, eight of nine (89%) had elevated estrogen receptor levels. This contrasts with patients who had stable or progressive disease as only 59% of them had measurable estrogen receptors (P = 0.16).

The role of laparoscopic lymphadenectomy in the management of cervical carcinoma

Laparoscopic lymphadenectomy was performed on 18 patients with invasive carcinoma of the cervix prior to definitive radiation therapy and/or radical hysterectomy. Ten patients underwent pelvic and para-aortic lymphadenectomies prior to planned radiotherapy. Two of these patients had grossly positive pelvic nodes, and one had a microscopically positive para-aortic node. Eight patients with early disease were considered candidates for radical hysterectomy and underwent laparoscopic lymphadenectomy. Three of these patients were found to have positive pelvic lymph nodes and the hysterectomy was abandoned. Five patients underwent radical hysterectomies immediately following their laparoscopic procedures. The average number of lymph nodes removed laparoscopically in these patients was 31.4; the average number of additional lymph nodes resected at laparotomy with the radical hysterectomy was 2.8. A single microscopically positive parametrial lymph node was found on permanent section in 1 patient with radical hysterectomy. No significant complications were associated with the laparoscopic lymphadenectomies. Nine of the 13 patients who underwent laparoscopic procedures only were discharged on Postoperative Day 1. The ability to perform pelvic and para-aortic lymphadenectomy allows for complete surgical staging of carcinoma of the cervix laparoscopically.

Complications of combined radical hysterectomy—Postoperative radiation therapy in women with early stage cervical cancer

Fifty patients with cervical cancer were treated with radical hysterectomy and lymphadenectomy followed by postoperative radiation therapy for high risk factors (nodal metastases, lymphvascular space invasion, close or involved margins) at the University of Alabama at Birmingham Medical Center from 1969 to 1984. Fifteen (30%) of the patients treated had serious complications, 8 (16%) requiring an operation, and 1 (2%) dying as a result of treatment-related problems. This combined modality approach is associated with significant complications.

A randomized comparative trial of carboplatin and iproplatin in advanced squamous carcinoma of the uterine cervix: a Gynecologic Oncology Group study.

A total of 394 patients with advanced, measurable squamous carcinoma of the uterine cervix and no prior chemotherapy were randomized to therapy with either carboplatin or iproplatin. There were 23 patients ineligible for the study and 10 patients who were not evaluable; the remaining 361 patients were evaluable for response and adverse effects. Randomization was well balanced for age, performance status, and prior therapy. Both platinum analogs were given every 28 days with starting doses of 400 mg/m2 for carboplatin (340 mg/m2 if the patient underwent prior radiation) and 270 mg/m2 for iproplatin (230 mg/m2 if the patient underwent prior radiation). These doses are equivalent to cisplatin doses of 75 to 100 mg/m2. Hematologic toxicity was dose-limiting, among which thrombocytopenia was slightly more common than leukopenia. Gastrointestinal toxicity was also prominent with both agents; however, iproplatin was significantly more toxic than carboplatin (P less than .001). Renal, otic, and peripheral nervous system toxicities were absent or infrequent with both analogs. No electrolyte abnormalities were observed. The percentage of planned dosages that were actually administered was 100% of carboplatin doses and 85% of iproplatin doses (P less than .0001). The reduction in iproplatin dose was apparently due to gastrointestinal toxicity. Response rates were similar for both agents (15% for carboplatin, 11% for iproplatin) and appear to be inferior to those noted with the parent compound, cisplatin.

Oral folic acid supplementation for cervical dysplasia: A clinical intervention trial

OBJECTIVE We attempted to evaluate the effect of oral folic acid supplementation on the course of cervical dysplasia. STUDY DESIGN A total of 235 subjects with grade 1 or 2 cervical intraepithelial neoplasia were randomly assigned to receive either 10 mg of folic acid or a placebo daily for 6 months. Clinical status, human papillomavirus type 16 infection, and blood folate levels were monitored at 2-month intervals. Outcome data were subjected to chi 2 analysis. RESULTS The prevalence of human papillomavirus type 16 infection initially was 16% among subjects in the upper tertile of red blood cell folate versus 37% in the lower tertile (trend p = 0.035). After 6 months no significant differences were observed between supplemented and unsupplemented subjects regarding dysplasia status, biopsy results, or prevalence of human papillomavirus type 16 infection. CONCLUSION Folate deficiency may be involved as a cocarcinogen during the initiation of cervical dysplasia, but folic acid supplements do not alter the course of established disease.

Clinical and histopathologic factors predicting recurrence and survival after pelvic exenteration for cancer of the cervix

&NA; Between September 1969 and January 1, 1986, 143 pelvic exenterations for recurrent cervical cancer were performed by the gynecologic oncologists at the University of Alabama at Birmingham. Of this group, 78 patients underwent total pelvic exenteration, 63 patients had anterior exenteration, and two had posterior exenteration. The overall operative mortality rate was 6.3%, mostly associated with total pelvic exenteration. The 5‐year survival rates were 50% overall, 63% with anterior exenteration and 42% with total exenteration. Univariate and multivariate analyses were performed to identify clinical and histopathologic factors predictive of prolonged survival. Using three clinical factors (duration from initial radiation therapy to exenteration, size of the central mass, and presence of preoperative sidewall fixation), low‐, intermediate‐, and high‐risk groups were constructed; the 5‐year survival rates for these groups were 82, 46, and 0%, respectively. Inclusion of one histopathologic factor (margin status of the surgical specimen) added to the ability to predict 2‐ and 5‐year survival rates. The best candidates for cure by pelvic exenteration were those with recurrent small (less than 3 cm), mobile central masses who were a year or longer from the time of their previous radiation therapy. Attempts to resect bulky pelvic recurrences that impinge on the pelvic sidewall, especially in the case of persistent or early recurrent disease (within 6 months), or continuation of exenterative procedures in women known to have nodal metastases or extrapelvic spread, are generally futile. For those women falling between the two extremes, sound clinical and operative judgment is imperative in regard to selecting the treatment offering the best quality of life. (Obstet Gynecol 73:1027, 1989)

An evaluation of human papillomavirus testing for intermediate- and high-risk types as triage before colposcopy☆

OBJECTIVE Our purpose was to evaluate the role of testing for intermediate- and high-risk human papillomavirus by use of a hybrid capture technique for predicting which patients with abnormal Papanicolaou smears are most likely to have squamous intraepithelial lesions or cancer. STUDY DESIGN Cervical cytologic studies, hybrid capture tests, and colposcopically directed biopsies were performed on 311 women referred to the colposcopy clinics with abnormal cytologic study results. RESULTS There was a highly significant correlation (p < 0.0001) between a positive human papillomavirus test and the finding of squamous intraepithelial lesions or invasive cancer. The sensitivity of human papillomavirus testing to detect high-grade squamous intraepithelial lesions was 74% when it was used alone and increased to 91% when coupled with abnormal cytologic study results of low- or high-grade squamous intraepithelial lesions or cancer. In 44 women with atypical squamous cells of undetermined significance on cytologic study, human papillomavirus testing identified six of 10 who had high-grade squamous intraepithelial lesions. For the 96 patients with low-grade squamous intraepithelial lesions, human papillomavirus testing was successful in identifying 29 of the 37 with high-grade squamous intraepithelial lesions (sensitivity 0.76). CONCLUSION Testing for intermediate- and high-risk human papillomavirus types by hybrid capture improves the detection of high-grade squamous intraepithelial lesions in women with atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions over cytologic study used alone.

Primary Surgical Therapy of Ovarian Cancer: How Much and When

From July 1975 through December 1985, 328 patients with ovarian malignancies were treated. Of these, 302 had epithelial invasive malignancies and constitute the study group. The impact of the operative procedure, findings, and subsequent treatment is evaluated. Patients who underwent extensive debulking procedures such as bowel resection and peritoneal stripping did not have improved survival compared with those patients who did not undergo these procedures and yet had residual disease remaining (P = 0.7 and P = 0.34). Reoperating patients felt to be unresectable at the time of referral did not increase survival over reoperating patients after an attempt at chemotherapeutic reduction (P = 0.34).

A randomized comparison of a rapid versus prolonged (24 hr) infusion of cisplatin in therapy of squamous cell carcinoma of the uterine cervix: A gynecologic oncology group study

In this study, 331 patients with advanced or recurrent squamous cell carcinoma of the cervix no longer amenable to control with surgery or radiotherapy were randomized to receive cisplatin 50 mg/m2 as either a continuous infusion over 24 hr or a more rapid infusion at a rate of 1 mg/min. Antiemetic therapy was standardized for the initial course of both regimens as metoclopramide 60 mg at the time of and at 3 and 6 hours after initiation of cisplatin. The overall frequency of objective regression of disease was 18%; the response rate in each regimen was essentially identical. The continuous infusion regimen was associated with a significantly greater percentage of patients who experienced no nausea and vomiting (34% versus 18%, P = 0.002). Other adverse effects included nephrotoxicity, peripheral neuropathy, myelosuppression, and ototoxicity. Both the frequency and severity of these were essentially the same for each regimen.