Efficacy of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in women aged 15-25 years with and without serological evidence of previous exposure to HPV-16/18.

In the Phase III PATRICIA study (NCT00122681), the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine (Cervarix(®), GlaxoSmithKline Biologicals) was highly efficacious against HPV-16/18 infections and precancerous lesions in women HPV-16/18 deoxyribose nucleic acid (DNA) negative and seronegative at baseline. We present further data on vaccine efficacy (VE) against HPV-16/18 in the total vaccinated cohort including women who may have been exposed to HPV-16/18 infection before vaccination. In women with no evidence of current or previous HPV-16/18 infection (DNA negative and seronegative), VE was 90.3% (96.1% confidence interval: 87.3-92.6) against 6-month persistent infection (PI), 91.9% (84.6-96.2) against cervical intraepithelial neoplasia (CIN)1+ and 94.6% (86.3-98.4) against CIN2+ [97.7% (91.1-99.8) when using the HPV type assignment algorithm (TAA)]. In women HPV-16/18 DNA negative but with serological evidence of previous HPV-16/18 infection (seropositive), VE was 72.3% (53.0-84.5) against 6-month PI, 67.2% (10.9-89.9) against CIN1+, and 68.8% (-28.3-95.0) against CIN2+ [88.5% (10.8-99.8) when using TAA]. In women with no evidence of current HPV-16/18 infection (DNA negative), regardless of their baseline HPV-16/18 serological status, VE was 88.7% (85.7-91.1) against 6-month PI, 89.1% (81.6-94.0) against CIN1+ and 92.4% (84.0-97.0) against CIN2+ [97.0% (90.6-99.5) when using TAA]. In women who were DNA positive for one vaccine type, the vaccine was efficacious against the other vaccine type. The vaccine did not impact the outcome of HPV-16/18 infections present at the time of vaccination. Vaccination was generally well tolerated regardless of the woman's HPV-16/18 DNA or serological status at entry.

Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women.

BACKGROUND: The human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine was immunogenic, generally well tolerated, and effective against HPV-16 or HPV-18 infections, and associated precancerous lesions in an event-triggered interim analysis of the phase III randomised, double-blind, controlled PApilloma TRIal against Cancer In young Adults (PATRICIA). We now assess the vaccine efficacy in the final event-driven analysis. METHODS: Women (15-25 years) were vaccinated at months 0, 1, and 6. Analyses were done in the according-to-protocol cohort for efficacy (ATP-E; vaccine, n=8093; control, n=8069), total vaccinated cohort (TVC, included all women receiving at least one vaccine dose, regardless of their baseline HPV status; represents the general population, including those who are sexually active; vaccine, n=9319; control, n=9325), and TVC-naive (no evidence of oncogenic HPV infection at baseline; represents women before sexual debut; vaccine, n=5822; control, n=5819). The primary endpoint was to assess vaccine efficacy against cervical intraepithelial neoplasia 2+ (CIN2+) that was associated with HPV-16 or HPV-18 in women who were seronegative at baseline, and DNA negative at baseline and month 6 for the corresponding type (ATP-E). This trial is registered with ClinicalTrials.gov, number NCT00122681. FINDINGS: Mean follow-up was 34.9 months (SD 6.4) after the third dose. Vaccine efficacy against CIN2+ associated with HPV-16/18 was 92.9% (96.1% CI 79.9-98.3) in the primary analysis and 98.1% (88.4-100) in an analysis in which probable causality to HPV type was assigned in lesions infected with multiple oncogenic types (ATP-E cohort). Vaccine efficacy against CIN2+ irrespective of HPV DNA in lesions was 30.4% (16.4-42.1) in the TVC and 70.2% (54.7-80.9) in the TVC-naive. Corresponding values against CIN3+ were 33.4% (9.1-51.5) in the TVC and 87.0% (54.9-97.7) in the TVC-naive. Vaccine efficacy against CIN2+ associated with 12 non-vaccine oncogenic types was 54.0% (34.0-68.4; ATP-E). Individual cross-protection against CIN2+ associated with HPV-31, HPV-33, and HPV-45 was seen in the TVC. INTERPRETATION: The HPV-16/18 AS04-adjuvanted vaccine showed high efficacy against CIN2+ associated with HPV-16/18 and non-vaccine oncogenic HPV types and substantial overall effect in cohorts that are relevant to universal mass vaccination and catch-up programmes. FUNDING: GlaxoSmithKline Biologicals.

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.

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.

Autoimmune causes of recurrent pregnancy loss.

Recurrent pregnancy loss (RPL) is the loss of 3 or more spontaneous and consecutive pregnancies. There are many causes, such as genetic, anatomic, hormonal, medical and immunologic causes. Two theories, the alloimmune and the autoimmune theories, explain the immunologic cause. The Antiphospholipid Antibody (APA) Syndrome is considered as the autoimmune cause of RPL. It involves two antibodies, Lupus anticoagulant (LAC) and the anti-cardiolipin antibody (ACA). The rate of LAC is 7% and of ACA is 15%, among pregnant women. These two antibodies are believed to cause thrombosis in the maternal circulation, leading to the events that lead to the fetal losses. Women with these antibodies, along with other factors, are believed to be at high risk for RPL. The diagnostic criteria for the APA syndrome include elevated LAC or ACA serum levels and clinical findings of thrombosis, thrombocytopenia and RPL. Presently, the medical treatment of the APA syndrome includes heparin, low-dose aspirin, and immunoglobulins. There must also be an active attempt to search for other causes of RPL among patients with APA syndrome, such as anatomic, endocrinologic, anatomic and medical problems. Management of RPL should also include extensive counseling for the patient and her family.

Girding for the new millennium.

PIP: This paper presents the lecture of Dr. Genara Manuel-Limson, delivered during the Philippine Obstetrics and Gynecology Society's Annual Convention on November 16, 1999, at the Westin Philippine Plaza. Manuel-Limson's discussion focuses on her own insights into the existing objectives of the Society. She first reviews the objectives of the Society, acknowledges the efforts made by members in achieving these goals and identifies areas for continued improvement. With emphasis on the last objective, which is the attainment of national good through the involvement of the members in community health care, Manuel-Limson discusses the growing problem of cervical cancer in the country. It is noted that cervical cancer is the most common genital tract cancer in the Philippines, next only to breast cancer. Although it is universally accepted that cancer of the cervix is preventable, research shows that most women have little or no knowledge about cervical cancers. In addition, general knowledge about the correct use of a Pap smear is low and compliance with Pap smears is not common. To this effect, Manuel-Limson stresses the importance of public education aside from cancer prevention. Overall, she hopes that the Society will continue to strive for improvement in providing excellent and committed service for women's health.^ieng

Updates and controversies in the diagnosis and treatment of CIN.

PIP: This paper presents the discourse of Dr. Genera A. Manuel-Limson entitled "Updates and Controversies in the Diagnosis and Treatment of Cervical Intraepithelial Neoplasia (CIN)." Manuel-Limson's discussion on diagnostic procedures for CIN includes Pap smear, colposcopy, cervicography, human papilloma virus testing and endocervical curettage (ECC). It is noted that Pap smear is the most cost-effective cancer screening at present. However, there are cases such as the screening for high-grade squamous intraepithelial lesion, wherein colposcopy is indicated as a follow-up diagnostic test. Another issue discussed is the question of whether ECC should be routinely done. In this regard, Manuel-Limson believes that, unless colposcopy is not satisfactory, ECC does not need to be routinely done. She offers some indications for ECC as well as for colposcopy. In terms of CIN treatment, the author reviews basic treatment principles and some of the currently employed treatment options. She demonstrates that CIN treatment has shifted from surgery to a more conservative method. Routine hysterectomy is now rarely indicated, which is largely due to the recent introduction of the loop electrosurgical excision procedure.^ieng

Cancer of the cervix in pregnancy: a 31-year experience at the Philippine General Hospital.

OBJECTIVE: To determine whether pregnancy, manner of delivery, the type and timing of therapy would affect the course of cervical cancer. METHODS: Records of cervical cancer cases at the Philippine General Hospital from 1961 to 1990 were reviewed. RESULTS: Survival rate (SR) for cancer of the cervix in pregnancy was not different from that of the non-pregnant. Those who delivered abdominally and treated by surgery posted a higher SR compared to those delivered vaginally and treated by radiotherapy. Majority of those delivered abdominally or had surgery were in Stage I while majority of those delivered vaginally or had radiotherapy were in the late stages. Nodal metastasis was associated with poorer prognosis. CONCLUSIONS: Survival rates were not affected by pregnancy nor by the manner of delivery, the mode and timing of treatment, but were still largely determined by the stage and by the presence of nodal metastasis.