A monoclonal antibody (MAb), designated PR-6, produced against chick oviduct progesterone receptors [Sullivan, W. P., Beito, T. G., Proper, J., Krco, C. J., & Toft, D. O. (1986) Endocrinology (Baltimore) 119, 1549-1557] cross-reacts with the Mr 120,000 human B receptors. An immunomatrix prepared with PR-6 was used to purify progesterone receptors (PR) from T47D human breast cancer cells. Single-step immunoaffinity chromatography results in enrichment of B receptors (identified by immunoblot with PR-6 and by photoaffinity labeling with [3H]promegestone) to a specific activity of 1915 pmol/mg of protein (or 23% purity) and with 27% yield. Purity and yields as judged by gel electrophoresis and densitometric scanning of the B protein were approximately 1.7-fold higher due to partial loss in hormone binding activity at the elution step. A second purification step by diethylaminoethyl chromatography gives further enrichment to 3720 pmol/mg of protein (or 44% purity) to yield essentially two proteins, 120-kilodalton (kDa) B receptors and a 76-kDa non-steroid binding protein, each in approximately equivalent amounts. B receptors purified under these conditions are transformed and biologically active. They were maintained as undegraded 120-kDa doublets and retained both hormone and DNA binding activities. Isolated B receptors were free of the 90-kDa non-steroid binding protein observed to be associated with 8S untransformed receptors in other systems and were free also of the non-hormone binding 105-108-kDa B antigen described previously to copurify with chick PR. These purified B receptors were used as immunogen for production of four monoclonal antibodies against human PR. Three of the MAbs, designated as B-30 (IgG1), B-64 (IgG1), and B-11 (IgM), are specific for B receptors. The fourth MAb, A/B-52 (IgG1), reacts with both A and B receptors. The IgG MAbs are monospecific for human PR since they recognize and absorb native receptor-hormone complexes, displace the sedimentation of 4S receptors on salt containing sucrose gradients, and, by immunoblot assay of crude T47D cytosol, react only with receptor polypeptides. Although mice were injected with B receptors only, production of A/B-52 which recognized both A and B receptors provides evidence that these two proteins share regions of structural homology. These new MAbs are valuable reagents for further studies of human receptor structure and function and for clinical immunodetection of PR in breast tumors.

Papanicolaou screening is feasible anywhere that screening for cervical cancer, the leading cause of cancer-related death among women in developing countries, is appropriate. After documenting that the Vietnam War had contributed to the problem of cervical cancer in Vietnam, we participated in a grass roots effort to establish a nationwide cervical cancer prevention program in that country and performed root cause analyses of program deficiencies. We found that real-world obstacles to successful cervical cancer prevention in developing countries involve people far more than technology and that such obstacles can be appropriately managed through a systems approach focused on programmatic quality rather than through ideological commitments to technology. A focus on quality satisfies public health goals, whereas a focus on technology is compatible with market forces.

Decades ago, cervical cancer was the leading form of cancer among women in both North Vietnam and South Vietnam. Currently, cervical cancer rates are considerably lower in the northern region of the country. We performed a case-control study to measure factors associated with the development of cervical cancer among Vietnamese women. Questionnaire-based interviews were conducted with 202 women in southern Vietnam and 97 women in northern Vietnam. Case subjects were women hospitalized with cervical cancer. Control subjects were women hospitalized with extrauterine neoplasms. Data were analyzed using logistic regression, and odds ratios for the development of invasive cervical cancer were measured. The development of invasive cervical cancer was significantly associated with military service by husbands during the Second Indochinese War and with parity status. Odds ratio for the development of cervical cancer among southern Vietnamese women whose husbands had served in the armed forces was 2.6 (95% CI ‫؍‬ 1.2-5.5). Odds ratio for the development of cervical cancer among northern women whose husbands had served in the armed forces was 3.9 (95% CI ‫؍‬ 1 Key words: cervical cancer; male factor; Second Indochinese War; VietnamCarcinoma of the uterine cervix is a public health problem of considerable significance in many developing countries. 1 Incidence rates of cervical cancer among women in Vietnam have been reported to display marked temporal and regional variation. Hospital-based tumor registries indicate that, several decades ago, cervical cancer was the most common form of cancer among women living in both northern 2 and southern 3 Vietnam. More recent population-based tumor registry studies indicate that cervical cancer is now the 4th most common form of cancer among women in northern Vietnam, with age-standardized incidence rates of 4.4 in 100,000. 4 Cervical cancer remains the most common form of cancer among women in southern Vietnam, with agestandardized incidence rates of 26 in 100,000. 5 It is generally accepted that cervical cancer is caused by persistent infection of uterine cervical epithelium by high-risk subtypes of human papillomavirus (HPV), a sexually acquired pathogen. 6 In Vietnam, regional differences in HPV prevalence correlate closely with regional differences in cervical cancer rates. 7 We undertook a questionnaire-based case control study to identify additional factors associated with the development of cervical cancer among women in Vietnam. MATERIAL AND METHODSInterviews were conducted between 1 June 1996 and 18 September 1996 at the Ho Chi Minh City Cancer Center in Ho Chi Minh City and at the National Cancer Institute in Hanoi. Women interviewed as case subjects were patients with biopsy-confirmed diagnoses of invasive cervical squamous cell carcinoma who were hospitalized at either cancer center. Case subjects were enrolled consecutively as they entered the cancer centers for treatment and included 41 northern women (40, or 98%, of whom responded to the questionnaire) and 72 southern ...

Cervical cancer is the leading cause of cancer-related death among women in developing countries. Although progress is optional in all settings, Papanicolaou screening is feasible anywhere that cervical screening is appropriate and should be implemented without further delay in high-risk communities with access to curative treatment services. Successful prophylactic cervical cancer vaccines, prospects for which remain uncertain, will not eliminate requirements for cervical screening. The feasibility of human papillomavirus test analysis has not been demonstrated in low-resource developing country settings. Because past failures of cervical screening in developing countries are attributable to failures in programmatic quality rather than to technological limitations of the screening test, a shift in paradigmatic focus from technology toward quality is mandatory. Because visual screening techniques coupled with immediate ablative treatment are rendered obsolete by an embedded quality-control paradox, a moratorium should be placed on all such programs. Considerable opportunity costs, borne by the underserved, are associated with prioritizing research of novel interventions in developing countries when satisfactory interventions already exist.

BACKGROUND Cervical carcinoma is the leading cause of cancer‐related death among women in the developing world. The absence of cervical screening in Vietnam and other developing countries is due in large part to the perceived expense of implementing Papanicolaou cytology screening services, although, to the authors' knowledge, the cost‐effectiveness of establishing such services has never been studied in a developing country. METHODS Using decision analytic methods, the authors assessed cost‐effectiveness of Pap screening from a societal perspective in Vietnam, the world's 9th most populous developing country (estimated 1999 population, 79 million). Outcomes measured included life expectancy, cervical carcinoma incidence, cost per woman, and cost‐effectiveness. RESULTS Total costs to establish a nationwide 5‐year interval Pap screening program in Vietnam will average less than $148,400 annually during the 10‐year time period assumed necessary to develop the program and may be considerably lower if only high risk geographic areas are targeted. Maintenance costs will average less than $0.092 annually per woman in the target screening population. Assuming 70% program participation, cervical carcinoma incidence will decrease from 26 in 100,000 to 14.8 in 100,000, and cost‐effectiveness will be $725 per discounted life‐year. Several assumptions used in this analysis constitute biases against the effectiveness of Pap screening, which in reality may be significantly more cost‐effective than reported here. CONCLUSIONS Contrary to widespread belief, Pap screening in developing countries such as Vietnam is extraordinarily inexpensive and appears to be cost‐effective. Because prospects are uncertain regarding useful alternatives to the Pap test, the evidence‐based argument for establishing conventional Pap screening services in developing countries such as Vietnam is compelling. Population‐based conventional Pap screening services have been established de novo in Vietnam and are now operational. Cancer 2001;91:928–39. © 2001 American Cancer Society.

The debate over the best route for cervical cancer prevention in developing countries may be considered part of a larger debate over whether the global health community has become enamored with the promise of new approaches at the expense of delivering available preventives today. Pap screening, which is feasible anywhere cervical screening is appropriate, is the only intervention currently available for the prevention of cervical cancer in developing countries, and the Pap test will be an essential component of future novel preventive approaches. Cervical cancer vaccination, the long-term effectiveness of which is uncertain, will not eliminate screening requirements and is currently not affordable in developing countries. Root cause analyses, which may appropriately inform the best routes for improving health in developing countries, document that failures of cervical cancer prevention efforts are not attributable to factors specific to the Pap test but to lapses in programmatic quality management to which all screening tests are vulnerable. The genuine promise of cervical cancer prevention for all the world's women therefore resides in skilled quality management rather than novel screening approaches. We propose a global consensus policy by which Pap screening services will be provided in any setting where cervical screening is appropriate but unavailable, with consideration given to novel preventive approaches as they mature. Opportunity costs, borne by the underserved, are associated with prioritizing research on new approaches in any setting where established preventives are feasible but unavailable.

In 1996, we documented that the burden of cervical cancer in Vietnam was associated with troop movements during the Vietnam War. Subsequently, establishment of Papanicolaou screening in southern Vietnam was associated with reductions in cervical cancer incidence from 29.2/100,000 in 1998 to 16/100,000 in 2003. This is one of the first English-language reports of a real-world cervical cancer prevention effort associated with a decisive impact on health outcomes in a contemporary developing country. Lessons learned: if our ideological commitment is to improve health outcomes as rapidly as possible among as many people as possible, then Papanicolaou screening (with or without HPV or visual screening) must be implemented without further delay in any setting where cervical screening is appropriate but unavailable; consideration must be given to HPV vaccination after, rather than before, full coverage of target demographic groups by screening services has been achieved and/or the possibility has been excluded that HPV vaccination may be ineffective for cancer prevention. Competing ideological commitments engender imprudent yet commercially useful alternative strategies prone to decelerate global reductions in mortality by suppressing the more-rapid uptake of less-expensive open-source technology in favor of the less-rapid uptake of more-expensive proprietary technologies with uncertain real-world advantages and unfavorable real-world operational limitations. Global cervical cancer prevention efforts will become more effective if global health leaders, including the Bill & Melinda Gates Foundation, embrace an ideological commitment to improving health outcomes as rapidly as possible among as many people as possible and assimilate the policy implications of that commitment.

The Viet/American Cervical Cancer Prevention Project embraces a dual mission. We seek to develop sustainable, cost-effective cervical cancer prevention services for women in Vietnam. Because the problem of cervical cancer in Vietnam is in part a legacy of the Second Indochinese War, we also seek to examine obstacles to reconciliation by presenting what most acknowledge to be a remedy in advance of what some will perceive to be an accusation. Certain research and commercial interests have produced obstacles to our dual mission in Vietnam. The Alliance for Cervical Cancer Prevention, supported by the Bill and Melinda Gates Foundation, has failed to endorse Pap screening for developing countries and is conducting clinical trials which may further disaffect medically underserved groups. Visual screening techniques combined with immediate ablative treatment methods are incompatible with the requirements of "first do no harm." Because the Pap smear will probably be a component of any future human papillomavirus (HPV)-based or visual- based screening programs, it serves the interests of those promoting noncytologic screening methods to also support the development of Pap screening services. Research on HPV screening in developing countries raises concerns of commercial exploitation. Because Pap screening is feasible wherever cervical screening is appropriate, it is inappropriate to delay the development of Pap screening services pending research into HPV vaccines or alternative screening technologies. Quality management is the point at which public health and diagnostic pathology intersect and will remain an indispensable element of cervical screening programs irrespective of the screening test(s) eventually used. Pap screening in developing countries is an ethical imperative without a substantial political constituency and will benefit from the engagement of organized cytology.