Confronting the consequences of the Covid-19 pandemic in women of reproductive age. Alarm for an imminent oncologic epidemic

The Covid-19 pandemic caused an unforeseen burden to the Health Systems worldwide with about 220 million people infected and more than 4.5 million human lives lost by now, according to the official WHO announcements. Additionally, not to mention the victims in remote and underdeveloped countries, where the number of patients is almost impossible to be calculated. As a result, the medical attention has shifted towards facing the consequences of the acute infections by SARS-CoV2, and massive healthcare resources were diverted in delivery of direct lifesaving services of absolute priority, at the expense of SRH and other healthcare services that were not considered essential. In response, many hospitals transformed their function to better combat the pandemic, while simultaneously most routine activities were canceled or postponed. In this regard, some WHO programs established at the pre-Covid era towards achieving the UN’s Sustainable Development Goals were disrupted. Thus, 23 million children missed their scheduled routine vaccinations, consequently risking the reappearance of many eradicated diseases, such as poliomyelitis, meningitis, rubella, measles, mumps, etc.

In this respect, millions of women suffered unmet need of contraception, due to impeded access to contraceptive services and supply shortages, leading to unplanned pregnancies with potential obstetric complications and disastrous consequences of unsafe abortions [1]. Furthermore, many examinations established during the pre-Covid-19 era, towards cancer prevention in women were short-staffed due to staff deployments to front line health care services against the surging waves of Covid-19. In addition, many women were reluctant to follow the scheduled preventive measures for chronic diseases, due to the necessity to stay at home because of school, childcare, and business closures, as well as public transportation difficulties. Even more patients with suspected or existing premalignant lesions avoided to request the regular medical attention through required health facility visits considering the risk of Covid-19 contagion. An example of special interest to young women, is the postponement of the regular preventive examinations for gynaecologic cancers such as cytology smears (Pap tests) and human papillomavirus (HPV) tests for cervical cancer as well as mammograms for breast cancer, the two most common gynaecologic malignancies worldwide. It should be noted that the total number of the National Breast and Cervical Cancer Early Detection Program (NBCCEDP) funded breast and cervical cancer screening tests declined by 87% and 84% respectively during April of 2020 in the US compared to the previous 5-year average [2].

Most medical organizations have established guidelines regarding cancer prevention. For example, the US Preventive Services Task Force (USPSTF) recommends that women aged 21–29 years should perform a cervical cytology examination every 3 years, while women aged 30 and over, should additionally receive primary high-risk HPV testing every 5 years ( USPSTF 2018) [3]. For breast cancer screening the USPSTF recommends that women of 40–49 years should receive mammograms biennially (USPSTF 2016) [4]. Lastly, women who are at a higher-than-average risk of cancer should receive the previously mentioned examinations more frequently. Thus, carriers of high penetration genes such as BRCA 1, BRCA 2, p53, PTEN, CDH1, CHEK2, PALB2, RAD5IC, BRIP1, ATM etc. should follow intensive screening programmes.

The delay in screening caused by the Covid-19 pandemic, may lead to the diagnosis and treatment of gynaecologic malignancies at a later stage of disease development, which may result to worse prognosis, which ultimately has both social and reproductive health consequences ie, the need for greater therapeutic interventions, such as more extended surgical operations (with negative impact on the female body image and psychology), more intense radiotherapy and chemotherapy with hazardous impact on the ovarian function (ie, hypoestrogenism, early menopause, decreased sexual desire and satisfaction with negative consequences at their relationship with partner etc.) Most interesting however, are the decreased fertility rates as well as the increased morbidity and mortality rates. In the US alone, the effects of Covid-19 on the delays of screening and treatment until recently, have been estimated to result in 10,000 additional deaths due to breast and colorectal cancers in the forseeable future [5]. Similar consequences are expected in Europe and all over the world. This equals to an imminent oncologic epidemic!

It is well known that the peak in breast cancer detection appears around the age of climacteric. Unfortunately, in recent years breast lesions develop in younger women, at higher percentages than before, affecting women during their reproductive age. Moreover, young patients show a higher proportion of triple negative, Grade 3, and HER2 overexpressing tumours, an increased risk for early relapse and in general a more unfavourable long-term outcome irrespective of the disease’s stage at diagnosis [6]. So, women of reproductive age are more at risk from breast cancer than previously anticipated. Additionally, breast cancer age-standardized incidence rates worldwide are highest amongst women under 39 years, compared to other malignancies. This may, among other reasons, be due to: (1) several social and environmental factors, such as the higher use of agricultural insecticides (whose formula resembles that of steroidal hormones thus, replacing them in binding to the ER- and Pr-Receptors of the breast’s epithelial cells), (2) the modern, social development of the past decades with the majority of women around the world having rightfully earned and exercised their human right to higher education and the pursuit of professional ambitions which has naturally led to later Stage concepts, full term pregnancies, and breastfeeding. These delays have interestingly also proven to increase the risk of breast cancer.

Recently published data indicate that during the first wave of Covid-19 pandemic the number of women participating to the established routine cancer preventive examinations was lower than before, but the patients already presented a more advanced stage of the disease compared to the past years [7]. These findings are expected to worsen due to the continuing delays in performing the established examinations during the Covid-19 preventive era. In addition, with Contraception less accessible and consequently less used, an increase in cases of ovarian, Fallopian tubes and endometrial cancers is anticipated, given the lack of the undoubtably protective effect of contraception on the pathogenesis of these malignancies.

It is comforting to know, that recent advancements in fertility preservation can help women affected by breast cancer to overcome the side effects of chemotherapy treatment through ’embryo cryopreservation’ (with a success rate of >40% per embryo transfer), ‘oocyte cryopreservation’ , ‘ovarian tissue cryopreservation’ (before the start of treatments) and ‘ovarian suppression with GnRH analogues’ (during chemotherapy). Yet, despite all the above, it is by far better to prevent the cancers in the first place or even to timely diagnose them than it is to resort to these fertility preserving treatments.

In conclusion we must unite our efforts towards confronting the consequences of the delays in performing the established pre-Covid-19 routine measures of preventive medicine. Awareness must be spread through the available channels (ie, media, internet, journals, e-seminars), to inform the women at risk. We must run this marathon in the speed of a 100 m sprinter to cover the lost ground caused by the postponement of the screening examinations in every field of female health, ie, ‘breast cancer’, ‘cancer of the uterine cervix’, ‘cancer of the endometrium’, ‘ovarian and fallopian tubes carcinomas’, etc. We are far behind this goal and many women may already be in advanced stages of cancer that could (and possibly can still) be treated successfully. The sooner, the better. The prevention, early detection, and timely diagnosis of gynaecological cancers that affect the quality of life and the reproductive potential of young women are within our society’s scientific scope.

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