COVID-19 in patients with cancer: first report of the ESMO international, registry-based, cohort study (ESMO-CoCARE).

BACKGROUND: ESMO COVID-19 and CAncer REgistry (ESMO-CoCARE) is an international collaborative registry-based, cohort study gathering real-world data from Europe, Asia/Oceania and Africa on the natural history, management and outcomes of patients with cancer infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). PATIENTS AND METHODS: ESMO-CoCARE captures information on patients with solid/haematological malignancies, diagnosed with coronavirus disease 2019 (COVID-19). Data collected since June 2020 include demographics, comorbidities, laboratory measurements, cancer characteristics, COVID-19 clinical features, management and outcome. Parameters influencing COVID-19 severity/recovery were investigated as well as factors associated with overall survival (OS) upon SARS-CoV-2 infection. RESULTS: This analysis includes 1626 patients from 20 countries (87% from 24 European, 7% from 5 North African, 6% from 8 Asian/Oceanian centres), with COVID-19 diagnosis from January 2020 to May 2021. Median age was 64 years, with 52% of female, 57% of cancer stage III/IV and 65% receiving active cancer treatment. Nearly 64% patients required hospitalization due to COVID-19 diagnosis, with 11% receiving intensive care. In multivariable analysis, male sex, older age, Eastern Cooperative Oncology Group (ECOG) performance status ≥2, body mass index (BMI) <25 kg/m2, presence of comorbidities, symptomatic disease, as well as haematological malignancies, active/progressive cancer, neutrophil-to-lymphocyte ratio (NLR) ≥6 and OnCovid Inflammatory Score ≤40 were associated with COVID-19 severity (i.e. severe/moderate disease requiring hospitalization). About 98% of patients with mild COVID-19 recovered, as opposed to 71% with severe/moderate disease. Advanced cancer stage was an additional adverse prognostic factor for recovery. At data cut-off, and with median follow-up of 3 months, the COVID-19-related death rate was 24.5% (297/1212), with 380 deaths recorded in total. Almost all factors associated with COVID-19 severity, except for BMI and NLR, were also predictive of inferior OS, along with smoking and non-Asian ethnicity. CONCLUSIONS: Selected patient and cancer characteristics related to sex, ethnicity, poor fitness, comorbidities, inflammation and active malignancy predict for severe/moderate disease and adverse outcomes from COVID-19 in patients with cancer.

Causes of cervical cancer in the Philippines: a case-control study.

BACKGROUND: Among the numerous human papillomavirus (HPV) types, only types 16 and 18 have been formally classified as human carcinogens. To evaluate the associations of 33 HPV types and other risk factors with squamous cell carcinoma and adenocarcinoma of the cervix, we performed a hospital-based, case-control study in the Philippines. METHODS: The study included 356 case subjects who had histologically confirmed cervical cancer (323 incident cases of squamous cell carcinoma and 33 incident cases of adenocarcinoma/adenosquamous carcinoma) and 381 control subjects. Information on risk factors was obtained by personal interview. HPV DNA was detected in exfoliated cervical cells and biopsy specimens by use of a polymerase chain reaction assay. RESULTS: HPV DNA was detected in 93.8% of case subjects with squamous cell carcinoma and in 90.9% of case subjects with adenocarcinoma/adenosquamous carcinoma compared with 9.2% of control subjects, giving age-adjusted odds ratios of 156 (95% confidence interval [CI] = 87-280) for squamous cell carcinoma and 111 (95% CI = 31-392) for adenocarcinoma/adenosquamous carcinoma. Fifteen different HPV types were detected in squamous cell carcinoma, and six different HPV types were detected in adenocarcinoma/adenosquamous carcinoma. Among HPV types other than types 16 and 18, the associations of HPV with risk of squamous cell carcinoma were strongest for HPV45. In addition to HPV, high parity, low socioeconomic status, and smoking were also associated with both types of cervical cancer. CONCLUSIONS: As has been shown for squamous cell carcinoma, HPV is the central cause of adenocarcinoma/adenosquamous carcinoma of the uterine cervix. The observed associations of less prevalent HPV types with cervical cancer have important implications for cervical cancer prevention strategies.

Somatic mutations of fibroblast growth factor receptor 3 (FGFR3) are uncommon in carcinomas of the uterine cervix.

Germline mutations of the gene encoding human fibroblast growth factor receptor 3 (FGFR3) have been shown to be responsible for several related autosomal dominant forms of syndromic craniosynostosis and short limb dwarfism. Somatic activating mutations of FGFR3 were recently reported to occur in three of 12 (25%) uterine cervical carcinomas and nine of 26 (35%) bladder carcinomas, suggesting that constitutive activation of FGFR3 may be an important mechanism underlying the development and/or progression of these common epithelial malignancies. In order to investigate further a possible role for FGFR3 mutations in cervical carcinogenesis, we performed sequence-based mutational analysis of FGFR3 in 51 primary cervical carcinomas and seven cervical carcinoma-derived cell lines. The regions analysed (exons 7, 10, 13, 15, and 19) encompassed all previously described FGFR3 mutations. A single nucleotide substitution at codon 249, predicting a serine to cysteine amino acid substitution (S249C) in the FGFR3 extracellular domain, was identified in one primary tumor. Only wild type FGFR3 alleles were identified in the remaining tumors and cell lines. The S249C mutation is the only FGFR3 mutation described to date in cervical carcinomas. These findings suggest that while activating mutations of FGFR3 occur in cervical cancer, they may not be as common as initially reported.

Hospital visitor-companions as a source of controls for case-control studies in the Philippines.

Hospital visitor-companions are being used as a source of controls in an ongoing case-control study on breast cancer in the Philippines. As a tool for rapid epidemiologic assessment in obtaining research data for case-control studies, visitor-companions may serve as an alternative source of controls. To determine their generalizability and consistency, this proposed group was compared to neighbourhood controls and to hospital-patient controls. Hospital visitor-companions were comparable to neighbourhood controls in terms of cooperation in the interviews, height, weight, marital status, longest residence, education, cigarette smoking, alcohol intake, annual income, proportion with salaried jobs, ownership of house, land, and business, number of people living in the house, number of siblings, medical history, parity, menopausal status, breast feeding practices, and use of oral contraceptives. Neighbourhood controls however had longer interview durations than visitor-companion controls (p less than 0.05). Hospital-patient controls were less likely to breast feed, had lower alcohol intake, and had more exposure to chronic diseases and diagnostic x-ray than visitor-companion or neighbourhood controls (p less than 0.05). It was concluded that visitor-companions may usefully serve as an alternative source of controls for case-control studies when their limitations are taken into consideration during analysis.

Screening for genital human papillomavirus: results from an international validation study on human papillomavirus sampling techniques.

The objective of this study was to determine the validity of human papillomavirus (HPV) detection using exfoliated cervical cells compared with cervical biopsy specimens in women with normal cervix and to assess whether HPV detection rates using exfoliated cells is dependent on the number and order in which cervical scrapes are taken. Women undergoing hysterectomy for reasons other than cervical cancer were recruited in three hospitals in countries with varying risks of cervical cancer. After informed consent and at the time of surgery, three consecutive cervical scrapes were taken as well as four biopsy specimens, one in each of the quadrants around the cervical os. In this study, 331 women were recruited and provided 992 cell samples and 1324 biopsy samples. All scrapes and a sample of biopsy specimens (n = 103) were tested by polymerase chain reaction enzyme immunoassay using a general primer (GP5+/ bio6+). Type-specific tests were performed for 14 HPV types at the subpicogram level in one test and individually. Positive samples were verified using Southern blot hybridization. The prevalence of HPV DNA was 6.3% in cervical cells. Of 19 HPV positive samples in the scrapes, 17 were confirmed in the biopsy specimens. The agreement, as measured by the Kappa statistic, was 0.90 (P < 0.0001). The concordance in detecting HPV infection between scrapes and biopsy specimens was 97.5%, and the concordance in categorizing the samples as negatives was 94.4%. These values were unchanged when the order in which scrapes were taken was compared. Among women without cervical cancer, HPV DNA detection rates do not vary if exfoliated cells or random biopsy specimens are taken as the primary testing specimen. Screening programs based on highly sensitive HPV DNA detection technology in cell scrapes should expect a minimal underdetection.

Acetic-acid guided visual inspection vs. cytology-based screening for cervical cancer in the Philippines.

OBJECTIVES: To compare the validity and acceptability of acetic-acid visualization (VIA), magnified acetic-acid visualization (VIAM), spatula+cotton swab-Papanicolaou (Pap) smear (SS), and cervical brush-Pap smear (CB) in the detection of precursor/early cervical cancer lesions. METHODS: A total of 12992 women aged between 25 and 65 years from 14 Philippine centers were randomly allocated to the four tests. The gold standard was colposcopy with biopsy for positive/suspicious cases. RESULTS: Sensitivity rates [95% confidence intervals (CIs)] were 37 (CI, 26.8-48.5), 34.1 (CI, 24.8-44.8), 14.3 (CI, 6.4-27.8), and 19.1 (CI, 9.2-34.6) for VIA, VIAM, SS, and CB, respectively. Specificity rates were 90.7 (CI, 89.6-91.7), 90.7 (CI, 89-91.1), 97.5 (CI, 96.8-98), and 97.9 (CI, 97.3-98.4), respectively. Kappa for the Pap smear (PS) within centers ranged from -0.154 to 0.783, and between centers from -0.028 to 0.364. Screeners preferred CB; screened-women preferred VIA. CONCLUSIONS: The acetic-acid visualization and VIAM methods are recommended for initial cervical cancer screening in the Philippines.

Oral plus intramuscular medroxyprogesterone acetate (high dose Farlutal) in advanced breast cancer.

The efficacy and tolerability of the combined scheme of administering high dose medroxyprogesterone acetate in advanced breast cancer is evaluated.

Knowledge, attitudes and practices on breast cancer and breast examination of nurses and midwives in Metro Manila.

This cross-sectional panel study determined the baseline knowledge about breast cancer and the attitudes on breast examination of nurses and midwives assigned at the different health centers in Metro Manila, and determined their sensitivity in detecting breast lumps after teaching them the Mamma-Care technique of breast examination, before they began to implement breast examination in the field. 225 nurses and midwives from a randomly selected 101 health centers in Metro Manila participated in a training seminar regarding breast cancer screening. They were given questionnaires to determine their baseline knowledge (multiple choice objective questionnaires) and attitudes (Liker-scale questionnaire) regarding their implementation of breast exam in the field. During the seminar, they were taught the Mamma-Care technique of breast examination with the aid of a videotape and lecture demonstration. They were then asked to examine silicone breast models which contain lumps of varying sizes (2 cm), mobility and hardness. Their sensitivity (through positive lumps detected by examination/total number of lumps in the breast model) in detecting lumps was then evaluated. Correct pretest knowledge on breast cancer symptoms, risk factors, treatment and screening were 83%, 64%, 86%, and 82%, respectively, which improved after training for 93%, 75%, 93%, and 92%, respectively. Trends in attitudes regarding implementation of breast exam were favorable. Sensitivity rates were 100% (33 nurses/midwives), 80% (48 n/m), 60% (n/m), 20% (17 n/m), and 0% (2 n/m). Overall sensitivity rate was 62%. Training and practice of skills among health center workers would enhance the Department of Health program on early detection of breast cancer in the Philippines.

Prevalence and risk factors for herpes simplex virus type 2 infection among middle-age women in Brazil and the Philippines.

BACKGROUND: Data comparing type-specific herpes simplex virus type 2 (HSV-2) seroprevalence and risk factors between comparable populations are largely unavailable, particularly from less-developed countries. GOAL: To examine the seroprevalence of HSV-2 infection and the risk factors for this infection among women in São Paulo, Brazil, and Manila, the Philippines. STUDY DESIGN: Altogether, 552 middle-aged women participating as control subjects in two cervical cancer studies were screened for type-specific HSV-2 antibodies. RESULTS: Herpes simplex virus type 2 seroprevalence was higher in Brazil (42%) than in the Philippines (9.2%). The mean ages of Brazilian (n = 181) and Filipino (n = 371) women were 52.4 and 46.6 years, respectively. Brazilian participants had more lifetime sexual partners, less education, and more often a husband with other sexual partners than Filipino women. Herpes simplex virus type 2 was independently associated with younger age at first intercourse in both countries. More than one lifetime sexual partner, a husband with other sexual partners, urban/semi-urban residence, and no history of condom use were HSV-2 risk factors in Brazil, but not in the Philippines, where long-term hormonal contraceptive use was associated with increased risk. CONCLUSIONS: The higher HSV-2 seroprevalence in Brazil than in the Philippines may be explained largely by differences in the sexual behavior of women and their husbands. Herpes simplex virus type 2 seroprevalence data may be used as a marker of past sexual behavior for the direct comparison of different population groups.

Prevalence and determinants of human papillomavirus genital infection in men.

Four-hundred-forty-five husbands of women with invasive cervical carcinoma, 165 of women with in situ cervical cancer, and 717 of control women (age range 19-82 years) were interviewed and a sample of exfoliated cells from the penis obtained in seven case-control studies conducted by the International Agency for Research on Cancer. The characteristics of human papillomavirus-positive and human papillomavirus-negative husbands were compared using odds ratios and 95% confidence intervals. Thirteen per cent of the husbands of control women, 18% of the husbands of women with invasive cervical carcinoma, and 21% of the husbands of in situ cervical carcinoma women were positive for penile human papillomavirus DNA. Human papillomavirus 16 was detected in 45 husbands, human papillomavirus 18, 31 or 33 in 19, and human papillomavirus 6/11 in 6, but the majority of human papillomavirus infection (158) was with other or unspecified human papillomavirus types. The same human papillomavirus type was seldom identified in both husband and wife. The strongest variation in penile human papillomavirus infection was by country, with percentages among the husbands of control women ranging between 3% in Spain and 39% in Brazil. Having had over 50 lifetime sexual partners, compared with only one, was associated with an odds ratio of 2.3.