A Need for Earlier Ovarian Cancer Detection
Dr. Saba Alzabin • January 19, 2019 • 5 min read
The lack of specific symptoms continues to be a driving factor in the late diagnosis of ovarian cancer. Only 20% of cases are detected early, and this is due to ineffective screening strategies to date.
To highlight the importance of early detection, the overall 5-year survival rate for ovarian cancer is 47%, but this becomes 92% when detected early. There is promising evidence that the serum levels of a naturally occurring protein, CA-125, are elevated in the blood of women with ovarian cancer. However, this is only statistically significant in late stage ovarian cancer and high serum levels of CA-125 are also associated with non-related conditions such as endometriosis and inflammatory pelvic disorder. Whilst higher than normal levels of CA-125 may be used as a marker for reproductive disorders, a transvaginal ultrasound (TVUS) remains the most reliable test for specific ovarian cancer detection.
Further research is needed for more accurate and early screening strategies to improve ovarian cancer prognosis.
Nabta is reshaping women’s healthcare. We support women with their personal health journeys, from everyday wellbeing to the uniquely female experiences of fertility, pregnancy, and menopause.
Get in touch if you have any questions about this article or any aspect of women’s health. We’re here for you.
Sources:
- Jacobs, I J, et al. “Ovarian Cancer Screening and Mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a Randomised Controlled Trial.” Lancet, vol. 387, 5 Mar. 2016, pp. 945–956., doi:10.1016/S0140-6736(15)01224-6.
- Menon, U, et al. “Risk Algorithm Using Serial Biomarker Measurements Doubles the Number of Screen-Detected Cancers Compared With a Single-Threshold Rule in the United Kingdom Collaborative Trial of Ovarian Cancer Screening.” Journal of Clinical Oncology, vol. 33, no. 18, 20 June 2015, pp. 2062–2071., doi: 10.1200/JCO.2014.59.4945.
- Survival Rates for Ovarian Cancer, by Stage. American Cancer Society, www.cancer.org/cancer/ovarian-cancer/detection-diagnosis-staging/survival-rates.html. Last reviewed: 11/4/2018.
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Will Taking the Pill Increase my Risk of Developing Cancer?
Will taking contraceptive pill increase developing cancer risk, It is estimated that as many as 140 million women worldwide take the [oral contraceptive pill](https://nabtahealth.com/the-oral-contraceptive-pill/). It is a simple, effective way for a female to control her own fertility and has also been utilised as a treatment for heavy periods, [acne](https://nabtahealth.com/why-do-i-get-acne-breakouts-before-my-period/) and [](https://nabtahealth.com/what-medications-are-recommended-for-endometriosis/)[endometriosis](https://nabtahealth.com/glossary/endometriosis/). However, safety concerns over its usage persist, and one of the major issues is a suspected link between the pill and cancer. So, what does the science say? Does taking the pill increase your risk of developing cancer, or can it actually serve a protective role? **The pill as an anti-cancer agent** ------------------------------------ **The pill reduces the risk of ovarian, endometrial and colorectal cancer.** * **Ovarian cancer**. Ever-users of the pill are significantly less likely to develop [ovarian cancer](https://nabtahealth.com/the-diversity-of-ovarian-cancer/) than never-users. In fact, studies have suggested that for every 5 years of pill use there is a 20% reduction in ovarian cancer risk. Furthermore, these protective effects are maintained for at least 30 years after discontinuation of pill use. * **Endometrial cancer**. The pill exerts a substantial protective effect against the development of [endometrial cancer](https://nabtahealth.com/a-guide-to-endometrial-cancer/). The risk is thought to be reduced by between 30 and 50%, depending on the duration of use. Protection lasts for at least 20 years after cessation of treatment. * **Colorectal cancer**. Ever-users of the pill are approximately 15% less likely to develop colorectal cancer than those that have never taken it. Whether increased duration of use has a beneficial effect is difficult to know as the quality of data from these studies is poor. **The pill’s carcinogenic effects** ----------------------------------- Oral contraceptive use is a risk factor for breast and cervical cancer. * **Breast cancer**. The association between breast cancer and the oral contraceptive pill is small, but significant. Studies suggest that those women who are currently on the pill are 20% to 24% more likely to receive a breast cancer diagnosis. The increased risk is lost once the pill is discontinued and, after ten years, prior pill users are at no greater risk than never users of getting breast cancer. The risk also falls significantly once a woman goes through the [menopause](https://nabtahealth.com/glossary/menopause/). Pill use is associated with clinically challenging types of breast cancer, including the [triple negative form](https://nabtahealth.com/breast-cancer-staging/), which usually has a worse prognosis and higher mortality rate. The exact mechanisms linking the two are unclear, although many breast cancers have a hormonal component. It is thought that increased lifetime exposure to oestrogens increases the risk of breast cancer, primarily because the hormone promotes or initiates tumour growth. Studies have failed to find an elevated risk of breast cancer in pill users with a family history of the disease. However, the data may be skewed by the fact that these women are less likely to use the pill due to their already increased susceptibility. The established link between [oestrogen](https://nabtahealth.com/glossary/oestrogen/) and breast cancer may [lead](https://nabtahealth.com/glossary/lead/) you to wonder whether using the progestin-only ‘mini pill’ would be a safer option. There have been very few studies on this form of contraception, probably because it is not as widely used as the combined pill (which contains [oestrogen](https://nabtahealth.com/glossary/oestrogen/) and progestin). The work that has been performed has suggested that women who take the mini pill still have a higher risk of breast cancer than those who have never used oral contraceptives, perhaps by as much as 21%. The link between progestins and breast cancer is poorly understood and likely to be complex. However, it is validated by studies on postmenopausal women who take hormone replacement therapy. Those on combined [oestrogen](https://nabtahealth.com/glossary/oestrogen/) plus progestin therapy have a higher breast cancer risk than those who take just [oestrogen](https://nabtahealth.com/glossary/oestrogen/). Thus, the mini pill should no longer be considered a safer contraceptive option for those with an elevated risk of developing breast cancer. * **Cervical cancer**. Taking the pill for five or more years is associated with a significantly increased risk of developing cervical cancer. The duration of use increases the risk, so that women who take the pill for 5 years have a 10% increased risk, but those who take it for longer, are more than 60% more likely to be diagnosed. Ten years after stopping the pill there is no increased risk of developing cervical cancer. One important thing to note is that as a risk, oral contraceptives will always be cofactors that interact with high risk [human papillomavirus](https://nabtahealth.com/when-should-i-get-a-pap-smear/) ([HPV](https://nabtahealth.com/glossary/hpv/)) strains to induce cervical carcinogenesis. This means that oral contraceptives in isolation are not a risk factor in women who are [HPV](https://nabtahealth.com/glossary/hpv/) negative; however, for those who are [HPV](https://nabtahealth.com/glossary/hpv/) positive, the pill can exacerbate the risk. Steroid hormone receptors (mainly [progesterone](https://nabtahealth.com/glossary/progesterone/)) are found in cervical tissue and are thought to enhance the expression of high risk [HPV](https://nabtahealth.com/glossary/hpv/), contributing to cancerous changes in the [cervix](https://nabtahealth.com/glossary/cervix/). **Conclusion: the pill and cancer** ----------------------------------- It is very difficult to state conclusively whether the pill should be used or avoided based on its associations with cancer. The net effect is likely to be positive, with one long-term, UK-based study finding that taking the pill resulted in a 12% reduction in overall cancer risk. It is also challenging to assess the absolute risk posed by oral contraceptive use. Cancer can have a long latency period, meaning the time between exposure to a particular risk factor and cancer diagnosis can span many years. Most women who develop cancer will have been exposed to multiple risk factors during their lifetimes, including [parity](https://nabtahealth.com/is-pregnancy-linked-to-developing-cervical-cancer/) (the number of times she has been pregnant and carried the baby to term), [obesity](https://nabtahealth.com/the-link-between-obesity-and-cancer-in-women/) and whether or not she has breastfed (breastfeeding can exert [protective effects](https://nabtahealth.com/benefits-of-breastfeeding-for-the-mother/)). Ascertaining how much of a role each of these factors plays in a later cancer diagnosis is likely to be extremely difficult. One final thing to consider is that the pill has changed in formulation over the decades since it was first utilised as a type of contraception. The specific synthetic hormones in use have changed, as has their concentration. Today, a triphasic pill is commonly used, whereby the hormone concentration changes across the month. This is designed to more closely mimic the normal ovulatory cycle. These different formulations will have differing risks and benefits. The consequence of this is that women who were prescribed the pill in its infancy, in the 1950s and 1960s should certainly not be compared to those taking it today in the 21st Century. Perhaps the advent of the mini pill came with initial optimism that the risks associated with the combined pill would be alleviated by removing the [oestrogen](https://nabtahealth.com/glossary/oestrogen/) component. Unfortunately, it appears that women taking this form of contraceptive have a comparable cancer risk to those taking the more commonly prescribed combined oral contraceptive pill. Nabta is reshaping women’s healthcare. We support women with their personal health journeys, from everyday wellbeing to the uniquely female experiences of fertility, pregnancy, and [menopause](https://nabtahealth.com/glossary/menopause/). Get in [touch](/cdn-cgi/l/email-protection#5f263e33333e1f313e3d2b3e373a3e332b37713c3032) if you have any questions about this article or any aspect of women’s health. We’re here for you. **Sources:** * Brynhildsen, Jan. “Combined Hormonal Contraceptives: Prescribing Patterns, Compliance, and Benefits versus Risks.” Therapeutic Advances in Drug Safety, vol. 5, no. 5, Oct. 2014, pp. 201–213., doi:10.1177/2042098614548857. * “Does the Contraceptive Pill Increase Cancer Risk?” Cancer Research UK, 4 Mar. 2019, [https://www.cancerresearchuk.org/about-cancer/causes-of-cancer/hormones-and-cancer/does-the-contraceptive-pill-increase-cancer-risk](https://www.cancerresearchuk.org/about-cancer/causes-of-cancer/hormones-and-cancer/does-the-contraceptive-pill-increase-cancer-risk). * Gierisch, J. M., et al. “Oral Contraceptive Use and Risk of Breast, Cervical, Colorectal, and Endometrial Cancers: A Systematic Review.” Cancer Epidemiology Biomarkers & Prevention, vol. 22, no. 11, Nov. 2013, pp. 1931–1943., doi:10.1158/1055-9965.epi-13-0298. * Knowlden, Hilary A. “The Pill and Cancer: a Review of the Literature. A Case of Swings and Roundabouts?” Journal of Advanced Nursing, vol. 15, no. 9, Sept. 1990, pp. 1016–1020., doi:10.1111/j.1365-2648.1990.tb01981.x. * Li, Li, et al. “Association between Oral Contraceptive Use as a Risk Factor and Triple-Negative Breast Cancer: A Systematic Review and Meta-Analysis.” Molecular and Clinical Oncology, vol. 7, no. 1, 12 May 2017, pp. 76–80., doi:10.3892/mco.2017.1259. * Murphy, Neil, et al. “Reproductive and Menstrual Factors and Colorectal Cancer Incidence in the Women’s Health Initiative Observational Study.” British Journal of Cancer, vol. 116, no. 1, 29 Nov. 2016, pp. 117–125., doi:10.1038/bjc.2016.345. * Mørch, L S, et al. “Contemporary Hormonal Contraception and the Risk of Breast Cancer.” New England Journal of Medicine, vol. 377, no. 23, 7 Dec. 2017, pp. 2228–2239., doi:10.1056/NEJMoa1700732. * “Oral Contraceptives (Birth Control Pills) and Cancer Risk.” National Cancer Institute, [https://www.cancer.gov/about-cancer/causes-prevention/risk/hormones/oral-contraceptives-fact-sheet](https://www.cancer.gov/about-cancer/causes-prevention/risk/hormones/oral-contraceptives-fact-sheet). * Roura, Esther, et al. “The Influence of Hormonal Factors on the Risk of Developing Cervical Cancer and Pre-Cancer: Results from the EPIC Cohort.” Plos One, vol. 11, no. 1, 25 Jan. 2016, doi:10.1371/journal.pone.0147029. * Schairer, Catherine. “Menopausal Estrogen and Estrogen-Progestin Replacement Therapy and Breast Cancer Risk.” Jama, vol. 283, no. 4, 26 Jan. 2000, pp. 485–491., doi:10.1001/jama.283.4.485. * Smith, Jennifer S, et al. “Cervical Cancer and Use of Hormonal Contraceptives: a Systematic Review.” The Lancet, vol. 361, no. 9364, 5 Apr. 2003, pp. 1159–1167., doi:10.1016/s0140-6736(03)12949-2. * Soroush, Ali, et al. “The Role of Oral Contraceptive Pills on Increased Risk of Breast Cancer in Iranian Populations: A Meta-Analysis.” Journal of Cancer Prevention, vol. 21, no. 4, 30 Dec. 2016, pp. 294–301., doi:10.15430/jcp.2016.21.4.294.
Diagnosing and Treating Breast Cancer During Pregnancy
Despite being the second most common malignancy affecting pregnancy, breast cancer during pregnancy is rare. Known as Pregnancy-Associated Breast Cancer (PABC), it affects approximately one in 3000 pregnancies. PABC is, in fact, defined as breast cancer that is diagnosed during pregnancy or in the first year postpartum. The aim with diagnosis and treatment of breast cancer during pregnancy is to follow, as closely as possible, the normal standards of care for patients of the same age who are not pregnant. That being said, some modifications may be required in order to minimise risks to the developing baby. **Diagnosis** ------------- Most breast cancers are diagnosed following self-examination and [identification of a lump](https://nabtahealth.com/is-the-first-sign-of-breast-cancer-always-a-lump/) in the breast tissue. During pregnancy, the breasts change in shape and size as they prepare for breastfeeding. It is not uncommon for them to feel lumpy and inconsistent as the milk producing ducts and glands start to fill with milk. This can make it difficult for women to establish which changes are normal and which are a cause for concern. All abnormal masses should be investigated, although, fortunately, 80% will be [benign](https://nabtahealth.com/glossary/benign/) in nature. The first diagnostic test a doctor will use is ultrasound. This uses soundwaves and is entirely safe for the unborn baby. It will characterise any unusual masses and identify whether there are features of concern within the mass. At around the same time a needle aspiration and/or core [biopsy](https://nabtahealth.com/glossary/biopsy/) may be taken. This enables doctors to explore the cells of the breast in more detail. Particular care will need to be implemented for analysing the results as, during pregnancy, it is not unusual for cells to become more proliferative in nature. Rapidly proliferating cells under normal conditions can serve as a warning sign that something is amiss. Mammograms will be used, however, they are known to lack sensitivity in pregnant or lactating females. As a mammogram involves radiation, doctors will endeavor to shield the baby from exposure. Newer digital mammograms might improve the sensitivity of the technique in women under 40 years of age. CT scans and bone scans, which are a normal part of the diagnostic process in non-pregnant females, are avoided during pregnancy, due to the dangers of radiation to the developing foetus. These methods are normally employed to check for [metastasis](https://nabtahealth.com/glossary/metastasis/), and thus, metastatic disease can be harder to detect in pregnant women. **Treatment** ------------- Most women with PABC will undergo surgery as the first-line treatment option, usually in the form of a modified radical mastectomy. It is generally safe to undergo anaesthesia whilst pregnant, but in order to limit the time you are under general anaesthetic, your doctor will probably recommend postponing reconstructive surgery until after delivery. [Radiotherapy](https://nabtahealth.com/glossary/radiotherapy/) is not recommended during pregnancy and wherever possible your doctor will attempt to delay this type of treatment until after delivery. This is because it increases the risk of [foetal malformations](https://nabtahealth.com/glossary/foetal-malformations/) and can delay [neurocognitive](https://nabtahealth.com/glossary/neurocognitive/) development. If breast preservation is desired, the disease is not advanced and diagnosis has occurred towards the end of pregnancy, it may be possible to treat with immediate lumpectomy and [radiotherapy](https://nabtahealth.com/glossary/radiotherapy/) after delivery. It has been shown that a six week window between lumpectomy and commencement of [radiotherapy](https://nabtahealth.com/glossary/radiotherapy/) does not have a detrimental effect on outcome. [Chemotherapy](https://nabtahealth.com/glossary/chemotherapy/) should not be given during the first [14 weeks of pregnancy](https://nabtahealth.com/articles/week-by-week-pregnancy-weeks-14-26/). It can cause severe [teratogenicity](https://nabtahealth.com/glossary/teratogenicity/) during organ development, which primarily occurs in the first trimester. In the second and third trimester, [chemotherapy](https://nabtahealth.com/glossary/chemotherapy/) can be administered. There have been no reports of later ill effects in children born to mothers who had [chemotherapy](https://nabtahealth.com/glossary/chemotherapy/) at this stage of their pregnancy. Most doctors will recommend stopping [chemotherapy](https://nabtahealth.com/glossary/chemotherapy/) at about week 36 to reduce the risk of infection or bleeding during delivery. Hormone therapy is not recommended for women who are pregnant or breastfeeding. Whilst, there are treatment options for women with PABC, additional work is required to establish a more effective treatment approach for these women. Certainly, as women postpone having children, the rates of PABC are likely to increase over the next few years. **Prognosis** ------------- The prognosis for women with PABC is generally lower than for women with breast cancer who are not pregnant. This is likely due to: * Less aggressive therapy being used due to concerns over the effect of harsher regimens on the developing baby. * Later stage of diagnosis because of difficulty in distinguishing physiologically-relevant changes from normal pregnancy-related changes. * The pregnancy having a direct effect on outcome, although knowledge regarding the exact mechanisms relating to this is currently lacking. * An increased percentage of [oestrogen](https://nabtahealth.com/glossary/oestrogen/) receptor negative cases. This is known to be associated with an increased risk of metastatic disease, which has a poorer prognosis. In terms of the developing foetus, women with PABC should be reassured that there are no reports of breast cancer spreading from the mother to the baby during pregnancy. In rare cases cancer cells will be found in the [placenta](https://nabtahealth.com/glossary/placenta/), so the doctor will always check this immediately after delivery. During pregnancy, a woman should remain under observation by a multidisciplinary team of healthcare professionals, including gynaecologists and oncologists to ensure that the support she receives is optimal for both her and her baby. Growth scans will be performed regularly to ensure that the baby is developing as he or she should be. If possible, the medical team will try to ensure that the woman delivers her baby as close to her due delivery date as possible. After delivery, treatment options will be reassessed. Get yourself the [post-surgery pack](https://nabtahealth.com/product/post-surgery-selfcare-pack-copy/) Nabta is reshaping women’s healthcare. We support women with their personal health journeys, from everyday wellbeing to the uniquely female experiences of fertility, pregnancy, and [menopause](https://nabtahealth.com/glossary/menopause/). Get in [touch](/cdn-cgi/l/email-protection#99e0f8f5f5f8d9f7f8fbedf8f1fcf8f5edf1b7faf6f4) if you have any questions about this article or any aspect of women’s health. We’re here for you. **Sources:** * “Breast Cancer.” Breast Cancer during Pregnancy | Cancer Research UK, 21 Nov. 2017, [https://www.cancerresearchuk.org/about-cancer/breast-cancer/living-with/breast-cancer-during-pregnancy](https://www.cancerresearchuk.org/about-cancer/breast-cancer/living-with/breast-cancer-during-pregnancy). * “Breast Cancer, Pregnancy and (Green-Top Guideline No. 12).” Royal College of Obstetricians & Gynaecologists, [https://www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg12/](https://www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg12/). * Johansson, A L V, et al. “Diagnostic Pathways and Management in Women with Pregnancy-Associated Breast Cancer (PABC): No Evidence of Treatment Delays Following a First Healthcare Contact.” Breast Cancer Research and Treatment, vol. 174, no. 2, Apr. 2019, pp. 489–503., doi:10.1007/s10549-018-05083-x. * Keyser, E A, et al. “Pregnancy-Associated Breast Cancer.” Reviews in Obstetrics & Gynecology, vol. 5, no. 2, 2012, pp. 94–99.
Is Pregnancy Linked to Developing Cervical Cancer?
Pregnancy linked to developing cervical cancer, The Lancet is one of the most widely read and well regarded medical journals and, as a result, work that gets published within it is generally considered to be high quality and scientifically robust. In 2002, the Lancet published the results of a study looking at the effects of parity (the number of times a woman has been pregnant and carried the baby to a viable [gestational age](https://nabtahealth.com/articles/gestational-diabetes-8-things-you-should-know/)) on cervical cancer rates. This followed work from the late 1980s and early 1990s that suggested that women who had been pregnant multiple times were more susceptible to _cervical cancer_. The findings published in the Lancet revealed that for [HPV](https://nabtahealth.com/glossary/hpv/)\-positive women there was a direct association between number of full-term pregnancies and risk of developing cervical cancer. This supported earlier work that stated that the risk of cervical cancer was more than 2-fold higher in women who had four or more children, compared to those who had none or one. **There are a few key points to note:** * The women at greatest risk are those who experience persistent [HPV](https://nabtahealth.com/glossary/hpv/) infection. High parity seems to act as a cofactor, interacting with [HPV](https://nabtahealth.com/glossary/hpv/) to induce cervical carcinoma. The relative risk is much lower in women who are [HPV](https://nabtahealth.com/glossary/hpv/)\-negative. * There is no evidence that high parity increases the risk of [HPV](https://nabtahealth.com/glossary/hpv/) infection. * The association is only seen with pregnancies classed as full-term. It is, therefore, likely, that the events triggering [carcinoma](https://www.cancercenter.com/carcinoma) progression happen during the second or third trimester, or even during delivery. It has been suggested that women who deliver vaginally are at a slightly higher risk than those who have a [caesarean](https://nabtahealth.com/glossary/caesarean/) section, however, this data is limited and the theory requires further validation. * Other factors may confound, or exacerbate the effect; for example, it has been suggested that prolonged [oral contraceptive](../the-oral-contraceptive-pill) use might have a multiplicative effect, increasing the risk further in women who are multiparous. Not all studies have identified a positive link; some do not find a significant association and others only find a link between high parity and certain types of cervical carcinoma. Some of the studies fail to consider whether a female has undergone frequent [pap screening](../when-should-i-get-a-pap-smear), or how many previous partners she has had. The biggest risk factor for the development of [HPV](https://nabtahealth.com/glossary/hpv/) is having multiple sexual partners. This data appears sound, even though the reported values are likely to be an under-estimation, due to an unwillingness of women to disclose this type of information. #### **Biological mechanism** There are plausible mechanisms for an involvement of pregnancy in the transition of normal cervical cells into cancerous lesions. [High risk](https://nabtahealth.com/articles/human-papillomavirus-hpv-and-cervical-cancer/) [HPV](https://nabtahealth.com/glossary/hpv/) infection is implicated in almost all cases of cervical cancer. However, not all women with [HPV](https://nabtahealth.com/glossary/hpv/) go on to develop cancer. It is thought that the high levels of [oestrogen](https://nabtahealth.com/glossary/oestrogen/) and [progesterone](https://nabtahealth.com/glossary/progesterone/) present throughout pregnancy, but particularly high in the last few weeks, cause cellular transformations on the surface of the [cervix](https://nabtahealth.com/glossary/cervix/) that last many years. This can cause prolonged exposure of the transformation zone in the [cervix](https://nabtahealth.com/glossary/cervix/) to [HPV](https://nabtahealth.com/glossary/hpv/) and increase the likelihood of persistent infection and progression to cancer. Another consideration is that the immunosuppression that is a natural part of pregnancy, can enhance the role of [](https://nabtahealth.com/articles/human-papillomavirus-hpv-and-cervical-cancer/)[HPV](https://nabtahealth.com/glossary/hpv/) in cervical carcinogenesis. One important theory proposed by the authors of the aforementioned Lancet study, is that smaller family sizes might explain, in part, why there has been a global decline in cervical cancer mortality and incidence. This decline is considered to be mainly due to an increased awareness of pap screening as well as the advent of the hugely effective [](../can-cervical-cancer-be-prevented)[HPV](https://nabtahealth.com/glossary/hpv/) vaccine; however, in countries where screening rates are low and the vaccine has not yet been introduced, a reduction in parity rates may provide an explanation. Nabta is reshaping women’s healthcare. We support women with their personal health journeys, from everyday wellbeing to the uniquely female experiences of fertility, pregnancy, and [menopause](https://nabtahealth.com/glossary/menopause/). Get in [touch](/cdn-cgi/l/email-protection#fd849c91919cbd939c9f899c95989c918995d39e9290) if you have any questions about this article or any aspect of women’s health. We’re here for you. **Sources:** * Brinton, Louise A., et al. “Parity As A Risk Factor For Cervical Cancer.” _American Journal of Epidemiology_, vol. 130, no. 3, Sept. 1989, pp. 486–496., doi:10.1093/oxfordjournals.aje.a115362. * Jensen, K E, et al. “Parity as a Cofactor for High-Grade Cervical Disease among Women with Persistent Human Papillomavirus Infection: a 13-Year Follow-Up.” _British Journal of Cancer_, vol. 108, no. 1, 15 Jan. 2013, pp. 234–239., doi:10.1038/bjc.2012.513. * Kasamatsu, Elena, et al. “Factors Associated with High-Risk Human Papillomavirus Infection and High-Grade Cervical Neoplasia: A Population-Based Study in Paraguay.” _Plos One_, vol. 14, no. 6, 27 June 2019, doi:10.1371/journal.pone.0218016. * Muñoz, Nubia, et al. “Role of Parity and Human Papillomavirus in Cervical Cancer: the IARC Multicentric Case-Control Study.” _The Lancet_, vol. 359, no. 9312, 30 Mar. 2002, pp. 1093–1101., doi:10.1016/s0140-6736(02)08151-5. * Roura, Esther, et al. “The Influence of Hormonal Factors on the Risk of Developing Cervical Cancer and Pre-Cancer: Results from the EPIC Cohort.” _Plos One_, vol. 11, no. 1, 25 Jan. 2016, doi:10.1371/journal.pone.0147029. * Russo, Evandro, et al. “Vaginal Delivery and Low Immunity Are Strongly Associated With High-Grade Cervical Intraepithelial Neoplasia in a High-Risk Population.” _Journal of Lower Genital Tract Disease_, vol. 15, no. 3, July 2011, pp. 195–199., doi:10.1097/lgt.0b013e31820918ea. * Trottier, Helen, et al. “Risk of Human Papillomavirus ([HPV](https://nabtahealth.com/glossary/hpv/)) Infection and Cervical Neoplasia after Pregnancy.” _BMC Pregnancy and Childbirth_, vol. 15, no. 1, 7 Oct. 2015, doi:10.1186/s12884-015-0675-0.