The importance of women’s psychosomatic health is under-recognised, and deserves promotion. Prevention and early management of certain disease conditions resulting from biological, psychological, and social factors that intermingle with cultural influences to generate these illnesses, are contemporary topics. In the modern healthcare environment, professionals managing these health conditions have to compete for resources, and in addition, practise economically sound management. Cancer and obesity are the topics of interest selected for examination here. Confronting these arguably avoidable illnesses in money-stretched healthcare systems are veritable challenges. Hence, their prevention and early management seem a judicious usage of any nation’s healthcare resources, and are worthy of discussion.
Prevention of diseases is learnt in the preclinical phase of the undergraduate medical curriculum but is often disregarded during disease management by the busy clinician who treats ailments on a day-to-day basis. Prevention of diseases is emphasised in ‘Preventive Medicine’—the branch of medical science, which deals with methods (such as vaccination) of preventing the occurrence of disease ; it is rationally coupled with ‘Social Medicine’ in preclinical teaching, as both are interrelated. Prevention of diseases can be ‘primary’, such as stopping smoking or being vaccinated to help prevent cancer; ‘secondary’, such as screening for cancer; or ‘tertiary’, when referring to disease management before complications develop. Many medical practitioners who are busy with the treatment of diseases may marginalise measures to prevent it, if the health condition does not fall within their daily remit. Nevertheless, the rising costs of treatment are driving up the need for disease prevention . The Commonwealth Fund estimated that the reduction of obesity and smoking would reduce healthcare expenditure by US$474 billion over 10 years , thereby justifying a business case for prevention.
When discussing the prevention of gynaecological cancer and obesity in women in this chapter, the advantages/disadvantages of primary or secondary prevention rather than tertiary prevention or treatment of disease will be underscored. While mind–body interactions form the basis of the psychosomatic origins of diseases (see Chapter 1) interpersonal and social interactions initiate or propagate ill-health through neuroendocrinological responses, which are further modulated by genetic and environmental factors. Therefore, the role of biopsychosociocultural factors that maintain women’s psychosomatic interactions, whether linked to cancer or to obesity, need to be identified and deciphered to enable prevention of associated ill-health.
The incidence of any disease, including cancer, is the number of new cases occurring within a certain period, expressed as an absolute number of cases per year or as a rate per 100 000 persons per year. With regards to cancer, the latter, which is an estimate of the average risk of developing cancer per year, is used for comparisons between countries or geographical areas, or within populations over time . Cancer or malignancy occurs when cells of a specific part of the body multiply uncontrollably to form a tumour with the potential to spread to other parts of the body, although not all tumours are malignant. Most malignancies are silent initially but can present as a lump, abnormal bleeding, a change in bowel function, fever, changes to the skin or unexplained weight loss; some of these symptoms can be caused by other factors that are benign conditions, which can confound and delay the diagnosis of cancer. Screening tests can detect certain cancers whether silent or symptomatic. According to global statistics published in 2015, a new cancer occurred in 14.1 million in 2012, and caused 8.2 million deaths, with breast cancer being the most common in females, and cervical cancer being the second most common [4,5]. The global incidence of cervical cancer in 2012  was 493 243, thus the second most common cancer in low–middle-income countries but the 11th most common cancer in high income countries, where there was a fall in the prevalence rate within the last decade due to the uptake of the cervical cancer screening programme.
Among the gynaecological cancers, the prevention and early treatment of precancerous lesions of the cervix will be the main focus of this chapter, while the less common vaginal and vulval premalignancies will be addressed only briefly.
Cervical intraepithelial neoplasia: terminologies/definitions and the aetiopathology
Cervical cancer is preceded by a precancerous condition referred to as cervical intraepithelial neoplasia or CIN. CIN represents a condition where the cells of the cervical epithelium undergo malignant changes but the basement membrane remains intact; the disease is localised. Another term used since the nineteenth century is carcinoma-in-situ (CIS), where neoplastic cells replace the normal cells of the cervical epithelium  but there is no breach in the basement membrane. ‘Dysplasia’ is a term previously used to categorise cervical epithelial cells which have undergone premalignant changes but to a lesser degree than CIS. CIN is divided into three grades: 1, 2, and 3, depending on the degree of pre-invasive changes, with 1 and 2 corresponding to mild and moderate dysplasia, whereas 3 corresponds to severe dysplasia and CIS. There is a greater chance of CIN1 regressing to normal epithelium spontaneously so it is known as a low-grade lesion, whereas 2 and 3 are classified as high grade. In North America, and a few other countries , the Bethesda classification of abnormal cervical epithelium is followed, where the abnormality is referred to as low-grade squamous epithelial lesions (LSIL) or high-grade squamous epithelial lesions (HSIL). When the incidence of CIN in the countries of Western Europe are compared, the UK stands out as having the highest incidence, with a peak occurring between the ages of 25 and 29 years, although only CIN3 had been officially recorded. Previously, there had been a continuing fall in the incidence of CIN3 in the UK but this was followed by static annual figures that could be due to the uptake of screening services by migrants who did not have screening in their countries of origin , and were diagnosed on arrival to the UK. The screening for CIN and its diagnosis and management, in particular, can result in considerable anxiety in many women, and can cause distress and depression.
Walboomers and colleagues reported that 99.7% of cervical cancer specimens from a Dutch sample of affected women showed the presence of human papilloma virus (HPV) . Pista and co-workers, from their multicentre observational study in Portugal , reported that 99.9% of specimens with CIN2, CIN3, or invasive cervical cancer had HPV infections (16, 18, and other subtypes). Nonetheless, the current HPV vaccines protect only against 77.4% HPV genotypes, which cause invasive cancer in their population, with cross-immunity for other oncogenic HPVs yet to be evaluated. Giorgi Rossi et al. from Italy  reported of a fall in invasive cervical cancer. HPV 16 was the most common HPV infection that was present in 66.4% of CIN2 or 3, and 66.8% of invasive cervical cancer, whereas HPV 18 was present in 7% and 11% of CIN2 or 3, and invasive cancer, respectively. Furthermore, the incidence of genital warts as a marker for HPV infection has been rising in both females and males with oncogenic HPV types 16 and 18 being present in approximately 15% .
HPV genital infection is acquired by sexual contact, and cleared by the majority of women within two years, unless their cell-mediated immunity is compromised. The HPV enters the cell cytoplasm (episomal) through a breach in the epithelium, and multiplies there but is cleared by the host’s immune system if the concerned woman is immunocompetent. When not cleared, the HPV enters the nucleus (integration) of the cell, and continues multiplying so the cell, instead of undergoing death after 40–60 cycles, is immortalised. Additionally, the virus’ E6 and E7 proteins bind to structures in the cell cytoplasm that regulate cell division and interfere with this function as well as causing DNA damage, which consequently converts the cell to a malignant cell line. It is not known why some cells progress to high-grade CIN, although it is recognised that being immunocompetent can prevent the progression to high-grade intraepithelial changes. The natural history of the precancerous condition indicates that 22% (29/131) of women with CIN3 would eventually (5–28-year follow-up) develop invasive cancer , but the exact time interval to the conversion to cancer, or which cervical cells will definitely become malignant, is not known for certain. While it is recognised that the majority of HPV infections result in CIN1, which regresses in approximately two-thirds of women to normal epithelium, and progresses in 10% to high-grade lesions, which of these cells in the epithelium will eventually progress to a high-grade CIN lesion cannot be definitely ascertained.
CIN can be associated with adenocarcinoma-in-situ or high-grade cervical intraepithelial glandular neoplasia (CIGN). CIGN may involve the whole cervical canal, or exist as skip lesions  though it is usually within 1 cm of the squamocolumnar junction. It is rare and treated by cone biopsy. Recurrence is common and reportedly occurs in 14%, even if the cone margins are free of disease. Cytological screening is unsatisfactory, and colposcopic features are not reliable, consequently impeding the formulation of optimal follow-up strategies. Regular endocervical cytology is advised during post-treatment follow-up along with the conventional practise of carrying out a cervical smear, and the colposcopic evaluation required for the screening of CIN.
Detection of CIN using cervical cytology and colposcopy
A screening test for CIN follows the usual principle of identifying a subgroup in a reference population that is at risk of a disease, and in this case, it is women who appear healthy who are targeted. Screening for CIN is carried out by cervical sampling, which was previously carried out by taking the Papanicolaou (Pap) smear but this method only included about 20% of cells from the sample. Liquid-based cytology , such as the ‘SurepathTM’ or ‘ThinprepPap test’ that are being used now reduces the proportion of inadequate smears, and the latter method also allows for screening of HPV and sexually transmitted disease (STD), if indicated. Quantitative HPV estimation can be of discriminatory value when borderline smears are reported.
Where 98% of cytological smears are adequate for diagnosis, approximately 10% may not be normal . These abnormalities can be broken down into: borderline nuclear abnormalities (3.3%); mild dyskaryosis (1.7%); moderate dyskaryosis (0.5%); severe dyskaryosis (0.5%); and invasion or glandular abnormalities (<0.1%). Borderline changes and mild dyskaryosis are very common in young women with the proportion of moderate dyskaryosis being highest in 20–29-year-old women, and severe dyskaryosis in 25–34-year-old women. False-positive rates vary from 7% to 27%, and false-negatives from 20% to 50%. In the UK, the cervical screening programme starts at 20–25 years of age, with regional variations, and is carried out every three years until the age of 49 years, and thereafter 5-yearly until the age of 64 years. Women with a cervical abnormality are referred for a colposcopy—a secondary investigation, in the UK. This is unlike certain other countries that do not have an organised cytological screening programme, and use colposcopy as the primary method of CIN surveillance.
A colposcope (binocular microscope) magnifies the cervical epithelium from ×4 to ×25 times. When examining the cervical epithelial cells , they are first visualised in their natural state, and then the application of saline under a ×16–×25 magnification enables a clear vision of capillaries/leucoplakia. Finally, visualisation after applying acetic acid is carried out when areas of high nuclear-cytoplasmic ratios turn acetowhite, and may indicate CIN or generating epithelium, or subclinical HPV infection. An experienced colposcopist can discriminate between different areas of acetowhite, and also takes into account the appearance of punctation and mosaicism that is more common with CIN, besides being able to identify bizarre-shaped vessels that are associated with cancer. Furthermore, Lugol’s iodine, if applied to the cervix, shows glycogen containing normal cervical cells as brown, whereas areas of CIN or cancer appear unstained, as they have little or no glycogen, so that the abnormal areas are better delineated from the normal epithelium.
Whether, when, and how to treat CIN can be contentious. Cervical screening has confirmed that the reversal to normal epithelium occurs in most individuals with low-grade CIN. There are no randomised trials of immediate colposcopy versus community-based cytological follow-up. The patient’s viewpoint should also be included in the decision-making about how and when to treat the CIN. There is some agreement that CIN1 should not be treated, as the majority resolve spontaneously; a follow-up should be instituted with a biopsy, if the area with CIN does not revert to normal in two years. Regarding CIN2 and 3, treatment is advised by excision , such as large loop excision of the transformation zone (LLETZ) using an electrodiathermy loop or a needle excision (NETZ) using a straight diathermy wire or by performing a cold knife cone biopsy when the specimen margins are not affected by heat. LLETZ, a European term, is synonymous with loop electrosurgical excision procedure (LEEP) – the North American term. Vaporisation using a laser is another option, as is cryotherapy, where the abnormal area is destroyed but both these ablative methods lack the advantage of obtaining a specimen for histopathological examination, which can confirm the presence of cytoplasmic/nuclear abnormalities of CIN, and give assurance that the specimen margins are free of disease. The ablative method can therefore initially be less reassuring to an anxious patient that the treatment provided has completely destroyed the abnormal area, and uncertainty may have an impact on such a patient’s psychosocial and sexual health. A treatment is considered successful when the cytology at six months post-treatment is negative.
A patient’s need to start a family is an important aspect to be considered when discussing the treatment of CIN along with her cytological report. Cervical excision could affect a future pregnancy by causing cervical incompetence, which can lead to a miscarriage or preterm labour [11,12,13], resulting in a preterm birth, and raise relevant neonatal health concerns. Heinonen et al.  in a retrospective register-based study, observed that a LEEP increased the risk of preterm delivery by twofold (n = 547; 7.2%) over the background rate of 4.6% (n = 30 151), and an odds ratio (OR) of 1.61 (confidence interval, CI, 1.47–1.75; number needed to treat to harm, 38.5). It was increased threefold, with a repeat LEEP that would imply more caution when carrying out such treatment procedures, and also taking care when performing a diagnostic LEEP. Jakobsson et al.  in a retrospective cohort study found that preterm delivery was increased threefold (RR 2.61; 95% CI, 2.02–3.20; number needed to treat for harm, 14) after LEEP conisation compared with the background rate (4.61%) of preterm delivery, and fivefold after a repeat LEEP. In another study, Noehr et al.  analysed population-based data, and reported that the preterm delivery rate was increased by twofold (6.9%) over the background rate of 3.5% (OR of 2.07; 95% CI, 1.88–2.27; LEEP vs no LEEP)).
A novel treatment of CIN, photodynamic therapy  has been reported. In this comparative study of conisation versus photodynamic therapy (PDT) using hexylaminolevulinate (HAL) for the treatment of CIN2 or 3, Soergel et al. reported that it was economically sound to provide the latter treatment. PDT left the cervix unscarred without being incompetent, thereby avoiding the increased risk of preterm labour associated with conisation. Thus PDT would be beneficial to women who desire a future pregnancy. Long-term follow-up of this treatment remains to be evaluated.
When to treat the cervix with CIN has been deliberated by Ebisch et al. , in order to assess overtreatment in a see-and-treat management strategy based on the patient’s cervical smear, colposcopic impression, and histology results. Their assessment method is compared with the current two-step treatment practised, where the initial colposcopy and biopsy is followed by treatment at a second visit based on the report of the initial biopsy; it has an overtreatment rate of 11–35%. The random effects model was used to account for heterogeneity in the studies reviewed. Overtreatment was considered where patients with no CIN or CIN1 had been treated. A total of 13 studies (n = 4611) were selected with the overtreatment rate being 11.6% (95% CI, 7.8–15.3%) in those with high-grade cervical smear and colposcopic impression, and 72.9% (95% CI, 68.1–77.7%) in those with a low-grade cervical smear and colposcopic impression. Overtreatment was 29.3% (95% CI, 16.7–41.9%) in those with high-grade cervical smear and low-grade colposcopic impression and 46.4% (95% CI, 15.7–77.1%) in those with low-grade cervical smear, and high-grade colposcopic impression. The authors’ conclusion was that for the high-grade cervical smear and the high-grade colposcopy group, the overtreatment rate with ‘see-and-treat’ was similar to the two-step procedure currently being practised. Hence, the former could be introduced into clinical practice for select patients. The authors also commented that their results are in accordance with the British National Health Service Cervical Screening Programme, which advises a see-and-treat management in only those with CIN2/3 or cervical glandular intraepithelial neoplasia, as does the advice from the European Federation for Colposcopy and Pathology of the Lower Genital Tract. In a mini-commentary from the USA , Waxman commented that see-and-treat is an option in select women only, although colposcopic impression is not a part of the assessment advised by the American Society for Colposcopy and Cervical Pathology; HPV status, if known, is however considered. Colposcopically directed biopsy may have a role where the cervical smear is high grade but if the colposcopic impression is low grade further research has been suggested.
The psychosociocultural aspects of receiving a diagnosis of CIN and its treatment
Variegated studies on psychological sequelae of the colposcopic follow-up of an abnormal cytology result from cervical screening , have been discussed in a recent systematic review by O’Connor and colleagues. The 16 studies selected had evaluated psychological well-being, using varied methods and concluded that adverse outcomes, particularly anxiety, can follow colposcopy and directed procedures. Five studies reported on depression post-colposcopy and four on distress. Of the four studies measuring post-procedure distress after colposcopy, one of them reported that one-third of patients were distressed. Worry and fear about cancer, and future fertility were reported by one-third of patients in another study. Five studies compared pre- and post-colposcopy psychosexual functioning, although no consistent pattern emerged from the evaluations. Only one study used a validated instrument, and reported that the post-colposcopy score indicated female sexual disorder. Ten studies, which investigated predictors of these adverse psychological/social outcomes concluded that further research was warranted. Temporal trends in psychological outcomes such as distress and anxiety after colposcopy were investigated in seven studies, which finalised their results as mixed findings. The heterogeneous findings from all these studies prevent formal statistical assessments. Despite the limitations of these studies, the conclusions helped unearth certain under-recognised problems associated with colposcopy and abnormal smears. Further clarification about the magnitude of these adverse psychological outcomes, their duration, and the reasons behind why some women were at increased risk of physical, mental, and social distress is required. The authors concluded that the cost of the negative psychological impact of cervical screening needed more attention in future studies.
Rahangdale commented  on O’Connor et al.’s review on colposcopically directed treatment of cervical dysplasia, and its impact on the woman. Distress, anxiety, and depression, together with worries about cancer/infertility and sexual dysfunction related to colposcopy and directed treatment were ‘potential harms’. The limitations of the studies on the various issues related to colposcopic management of abnormal cervical cytology is stressed, as it reflects on the findings of the systematic review, and on the complexities of equating the pros and cons of colposcopy with its invasive extension—LEEP. There is mention of the previous practise of annual cervical screening in the USA (now revised), which did not decrease the incidence of cervical cancer or mortality but inherently led to unnecessary treatment with long-term morbidity, such as physical discomfort, emotional distress, and preterm delivery; this was also described by O’Conner et al. Accordingly, adding HPV screening to current screening guidelines would complement efforts to prevent cervical cancer, and hence reduce the stress from colposcopy, and related treatment. Balancing the harm–benefit ratio is tenuous, and the value of O’Connor’s review in highlighting the emotional and relationship issues arising from colposcopy and directed procedures is stressed.
In a more recent case–control study , Frega et al. also included early loss (miscarriage) rate, and noted that there was no difference in this after LEEP (n = 475; 4.6%) when compared with the background miscarriage rate (n = 441; 4.1%) or after retaining a post-LEEP cervical canal length of 15–30 mm. However, those with a cervical canal length of under 15 mm, with removal of a wider volume of cervical tissue, had an increased risk of preterm delivery (OR 5.31; 95% CI, 1.01–28.07). Even though a cautious approach is advisable in carrying out a LEEP to reduce the risk of miscarriage or preterm delivery, it may not be possible to stop preterm contractions in all patients with progression to delivery even after applying a MacDonald cervical suture that encircles the cervix to stave off preterm birth.
Vaginal and vulval cancer, which are less common, also have premalignant stages, referred to as ‘vaginal intraepithelial neoplasia’ (VAIN) and vulval intraepithelial neoplasia (VIN). Their treatment is surgical with major biopsychosocial consequences, particularly if multicentric . Multicentric intraepithelial neoplasia (MIN) can effect a select group of females who are immunocompromised, e.g. due to HIV or those who are immunosuppressed for transplant surgery. Such precancerous changes can concomitantly effect the cervix, vagina, vulva, perineum, anal canal, and natal cleft. These females present with repeated abnormal smears, even after treatment of CIN. The chronicity of the disease can result in the patient requiring repeated smears/biopsies from the affected sites with abnormalities leading to repeat treatments; the resultant major psychosomatic sequelae necessitates a culturally sensitive approach by those involved in the management. Lesions of the perineum and anal canal may result in excision, skin-grafting, and temporary colostomies, with management by a multidisciplinary team of a gynaecologist, plastic surgeon, colorectal surgeon, stoma nurse, and a psychiatrist. Besides the effect of the diagnosis and treatment of premalignancy on the patient, the impact on the partner and their psychosexual health could be considerable, as with cancer (see Chapters 10 and 11). Moreover, other premalignant conditions can arise from the cellular structures of the perineum and introitus or adjacent thigh, and involve the vulvovaginal tissues. Although less common, they can progress  with metastasis, and cause major repercussions on the health of the affected individual. This includes wide-ranging limitations to the patient’s physical, mental, and social functioning, which relates to the extent of the disease and can distress her close family members (see Chapter 10).
Clinical vignettes 1 and 2 (Table 8.1) depict the impact of the management of premalignancy.
Table 8.1 Clinical vignettes: The impact of the diagnosis and treatment of premalignancy
Vignette 1: Pregnancy complications following treatment of CIN: British Caucasian
Vignette 2: Pregnancy complications, sequelae of a melanoma: British Caucasian
Presentation and management
Ms AW, a 37-year-old high school teacher, in her 2nd pregnancy, had a termination of pregnancy in her late teens; a steady relationship since 4 years; unsuccessfully tried for a baby and was investigated for subfertility; ovulation induction with clomiphene citrate and artificial insemination was unsuccessful
Mrs AH, a 34-year-old health professional, in her first pregnancy, resulting from ovulation induction
Psychosocial initiating and maintaining factors appropriate biopsychosocio-cultural care
Impact on the healthcare system
Implications for training
Was this form of management appropriate and what did it prevent?
Other forms of presentation
CIN2/3 can present as a vaginal discharge, particularly if HPV infection is present along with other STDs of the lower genital tract; the discharge could also be blood stained. When a benign to malignant transition occurs, other than itching and irregular margins, a melanoma can present with a change in characteristics of a previous mole, e.g. change in colour, enlargement, or a blood stained discharge.
In the vignettes shown in Table 8.1 both Ms AW and Mrs AH desired a baby. Premalignant changes were detected early, yet the outcomes were less than appropriate. CIN has a more indolent progress to malignancy, yet Ms AW wanted it treated by a one-stop procedure in order that she could have an IVF at the planned date; her cervical incompetence prevented a successful pregnancy outcome. The psychosomatic aspects of her loss would have to be minimised during her grieving process prior to her IVF. She may need additional support during her next pregnancy. As the risk of preterm cervical dilatation was documented with this pregnancy, she would have a cervical suture inserted earlier on in her next pregnancy along with tocolysis, as indicated. Would a longer period of observation of her CIN2 and excision at a later date have been the better option? Mrs AH’s itchy mole was detected early by her and it was rapidly brought to a multidisciplinary team discussion (SSMDT), and the medical treatment advised conformed to the option she had selected. Although malignant changes were not detected on checking the sentinel node, systemic micrometastasis may have been present to cause the rapid progression to advanced malignancy after metastases were detected in the liver. Would less exposure to sunbeds have prevented it? These questions will remain unanswered. Both Ms AW and Mrs AH had made informed decisions about the treatment of their premalignancies as the desire for a successful pregnancy outcome influenced their decisions. The characteristics of the malignancies related to their prognosis was of lesser relevance in the decision-making of these women. The psychosomatic approach can help understand the decision-making process of strong personality-types that endure adversity until persisting problems make them take another route; Ms AW and Mrs AH fell into such personality-types, and the medical team had to ethically accept their decisions.
Prophylaxis of CIN
If HPV is the main causative factor for CIN, it is to be expected that preventing such infection would reduce the incidence of CIN and the resultant progression to cervical cancer. HPV infection also makes the woman/adolescent more prone to develop VAIN/VIN so prophylaxis against HPV infection would also act as a preventative factor for premalignant changes resulting from such infection of the vagina and vulva. However, vaccination against HPV is currently designed to prevent infection caused by the specific genotypes targeted by the vaccine, namely types 16 and 18 with the bivalent vaccine, and types 6, 11, 16, and 18, with the quadrivalent vaccine. As cervical cancer is associated with types 16 and 18 in 70% of women , the prophylaxis from vaccination targets women with these infections. Its probable effect on herd immunity, and thus its impact on other prevalent carcinogenic genotypes in different populations it still to be evaluated. As the prevalence of precancerous HPV types in different communities is variable [6,7,8], allocating vaccine-generated immunity to cover other prevalent carcinogenic genotypes (30%) is implausible. Due to a lack of clarity in the multifactorial aetiopathogenesis of MIN, the currently administered HPV vaccine would only be suitable as a prophylaxis for 30%  of these patients. Furthermore, the unvaccinated male partner may additionally harbour HPV genotypes not targeted by the current quadrivalent vaccine, and infect his partner, despite her having been vaccinated. The HPV vaccination programme provided by the NHS in the UK  has only targeted females from the age of 11–13 years until the age of 26 years, with two doses being given to females at 12–13 years and three doses if vaccinated after 13 years. To date, it has not been considered cost-effective to vaccinate British males. A recommendation in a report by the Joint Committee on Vaccination and Immunisation is awaited.
In the USA, both sexes are offered vaccination , with the programme being directed to include females and males from the age of 11–12 years. It is also offered to females aged between 13–26 years of age and to males of 13–21 years of age, with the aim being to protect against HPV infections of the anal canal and oral cavity/oropharynx in both sexes, and penile infection in males. If uptake of the quadrivalent vaccine increases the immunity in the vaccinated individuals, such protection can last for ten years and prevent infection by an unvaccinated male, who is infected by the HPV genotypes that are included in the vaccine. However, the need for a booster dose at this juncture is still under evaluation, with no current guidelines available. If the contribution of the infected male as a carrier of HPV is ignored in the prevention strategy for HPV, he could infect with the HPV genotypes, which he harbours that are not included in his partner’s HPV vaccine, or if her period of immunity is over, and due care is not taken to use a condom during intercourse. An infection of the female partner by a strain of oncogenic HPV not included in the vaccine could create anguish, and probable dysphoric symptoms along with relationship problems in the couple, particularly if she was falsely reassured that vaccination would protect her from infection by all genotypes of HPV, and that she could have unprotected intercourse. Hence, reliance on the cervical screening programme and/or colposcopy remains of great value in enabling cancer prophylaxis by detecting/treating any areas of abnormal cytology with intraepithelial neoplasia, even after HPV vaccination.
The cost of the vaccines (US$140.00 per vial) may be prohibitive where medical care is not paid for by the state, particularly in low- or middle-income nations, thereby discouraging vaccination. In the UK, as HPV vaccination is paid for by the NHS so a low income is not a deterrent. In the USA, the uptake of HPV vaccination is variable, being around 32% in the female population, with substantially lower uptake rates in the uninsured, and in some females residing in the Southern states; likely reasons include refusal of parental permission or the cost of the three doses of vaccine .
Additionally, a prediction of a change in the natural history of the disease following vaccination has been surmised, as well as a reduced uptake in ethnic minority groups in the UK . Certain cultural beliefs and social control may thwart parental consent for vaccination [24,25]. A systematic review highlighted ethnicity, and limitations of healthcare coverage in various regions, as deterrents to the uptake of HPV vaccination . Other deterrents to the uptake could be side-effects, such as injection site redness/swelling/pain (frequent, if 1 in 10); fainting or non-epileptic seizures (less frequent if 1 in 100); urticaria (rare if 1 in 1000); serious allergic reactions, with troubled breathing besides facial swelling (very rare if 1 in 10 000); and fatality (extremely rare); these have been reported from a trial of Gardasil , and later by voluntary reporting. Pre-vaccination counselling should address these side-effects and any anxiety, especially when informing the parents of minors, who have to take the decision for their children.
Would not the barrier methods of contraception, if effectively practised, be a better prevention strategy against HPV, as there is global familiarity with it, and it has additional protective benefits? Barrier methods would also prevent other STD infections such as gonorrhoea and trichomoniasis as well as HIV that can co-exist with HPV infection. There is a low failure rate for prevention of pregnancy by barrier methods, and it could also protect against STD infections of the cervical cells  that, if pre-existing, could concurrently facilitate infection of the cervical cells with HIV. Similarly, a correct and consistent use of the condom is highly effective in preventing any failures in contraception, and would also be effective for preventing HPV infection . When condoms were compared with female-dependent methods of contraception (sponge or diaphragm) with regards to preventing STDs, using female-dependent methods significantly lowered the rates of both gonorrhoea and trichomoniasis ; these methods however cannot prevent HPV infection  of the lower genital tract. Comparatively, the same sponge and diaphragm can be used for three years , and are cheaper than female condoms but female condoms provide the additional benefit of also protecting against HPV infection. Currently, plant-based vaginal gels that could be used to prevent HPV infection  are being researched, and could be a cost-effective method, especially for low-resource settings. Epstein  reasoned that the primary prevention of HPV infection would entail the early targeting of youth by encouraging them to use condoms, and hence reduce the incidence of HPV infection with its potential progression to CIN. This may however be contrary to the interests of proponents who have propagated the use of HPV vaccines in preference to condoms as a form of primary prevention strategy to reduce HPV infection. Nonetheless, where a female and her consort have not been infected with HPV, and are faithful to each other, the risk of intraepithelial neoplasia of the lower genital tract is minimal.
In certain cultures, where an engagement ceremony for marriage is performed just before/soon after adulthood, and the couple have not had any other sexual relationships, primary prevention of HPV infection by monogamy is a possibility. Cultural promotion of such behaviour by certain societies, e.g. in South Asia , where child betrothal (the couple are teenagers) with marriage in adulthood (average age, 19 years in India), which is socially sanctioned is still prevalent. Such practice could encourage cost-effective prevention against STDs, including infection by HPV. Prophylaxis against HPV infection by maintaining monogamy has received scant attention. Understanding the various cultural attitudes behind such exclusive choices, and the commitment of loyalty to each other can be difficult to fathom for those with different sociocultural beliefs that encourage non-monogamous, risky sexual behaviour. Nevertheless, the question of early betrothal and adolescent marriage in certain cultures raises major psychosociocultural concerns, especially if the choice of the couple differs from the decision of parents/elders, and is not taken into account. In some African nations, child marriage (girl, <18 years) is common practice , with the major concerns being that usually the much older man, who has had multiple partners prior to the marriage, gives a dowry for the minor girl. She enters his life as a sexual partner, usually without her consent and this can increase the risk of STDs along with HPV in the girl who has also been denied education. This practice is commonly associated with poverty, so the girl cannot leave if unhappy in the relationship, as she cannot repay her dowry. As such, the prevalence of cervical cancer is high in African countries. For instance, the average age at marriage for a female is 15 years in Mali , with the older husband having had multiple sexual partners, and being infected with HPV (97%) besides having contracted AIDS/HIV infection; these infections are transmissible to his wife. Delaying the sexual debut, and using condoms may prevent HPV infection but cannot be practised where the male partner refuses to do so, and this can occur where marrying a minor female is the norm. Most African countries do not have the infrastructure to have a comprehensive cervical screening programme . Although the ceremonious commitment of a steady relationship in a monogamous young couple may be a cost-effective primary method of preventing HPV infection, it may be culturally confined to certain societies only.
Smoking is also related to CIN both indirectly and directly, and it is preventable. If early action is not taken, and the smoking becomes addictive (see Chapter 1) then quitting is difficult. It may need nicotine replacement with clinical help along with cognitive behaviour therapy, acupuncture, hypnosis and/or medication such as varenicline, along with close monitoring. Smoking indirectly interferes with the frequency of HPV infections, and thereby with the incidence of CIN that may progress to invasive cancer, or it can be a direct cause of the cancer . Equally, it has been reported  that the effect of past or current smoking along with HPV infection increases the risk of squamous cell carcinoma of the cervix (n = 1463) but has no effect on the incidence of adenocarcinoma; the sample size of adeno- or adenosquamous cervical carcinoma (n = 124) was comparatively small in that study . The direct effect of smoking on carcinogenesis is due to local immunosuppression, besides aberrant methylation of the tumour suppressor gene, p16 (CDNK2A), which then initiates a carcinogenic effect on the cervical epithelium . Furthermore, cervical carcinogenesis related to smoking can also be associated with other unhealthy lifestyles or when facing severe stress routinely with psychosocial effects that can lower innate immunity. The International Agency for Research on Cancer listed cervical cancer among those cancers causally related to smoking that deserves more research  to promote cancer prophylaxis. The natural history of HPV deserves attention  to define its carcinogenic role.
A widespread uptake and acceptance of the cervical screening programme over the last decade, has led to a reduction of the incidence of cervical cancer in most Western nations, thereby testifying to its usefulness in cancer prophylaxis. These methods of detection/treatment of premalignant areas will continue to be offered concomitantly with other newer developments in cancer prevention. It needs wider application globally after being modified to be culturally acceptable to different populations, and their healthcare providers.
The disease burden of obesity in gynaecology and obstetrics
Obesity is defined as a body mass index (BMI) of ≥30 kg/m2. It is said to exist when a person who is overweight (≥25 kg/m2) is unable to prevent a further increase in weight beyond the upper limit of this range (<30 kg/m2). ‘Extreme obesity’ is commonly used to categorise individuals with a BMI of ≥40 kg/m2. Obesity can start early, with 3% of children and adolescents being affected in the UK , and 16.9% in the USA . There has been stability in the upward trend of overweight and obese adults in developed countries within the last decade, with some nations now showing a downward trend [44,45,46,47,48,49]. Nevertheless, the prevalence still remains high with extreme obesity still continuing to rise. Unfortunately, the low- and middle-income countries are now showing a rise in overweight and obese children; these countries have been promoting the consumption of a low-cost energy-rich diet, which has been twinned with a lifestyle that discourages physical exercise. A review of the epidemiological literature between 1970 and 1992 reported that one-third of obese children and a half of obese adolescents  continue to be obese in adulthood. Hence, prevention and early action to reverse childhood obesity, with involvement of parents to aid a modification of contrary attitudes towards diet and exercise is required. Moreover, recourse to help through behavioural therapy, if indicated, could help stall the progression to overweight and obese adults . Globally, children and adolescents are greatly affected when obese, with a negative impact on their biopsychosocial health, particularly if teased by their peers; this can also impede school performance . Unless further preventive measures are instituted, one-third of the British population will be classified as obese by 2030 . Extreme obesity affects 6.3% of people in the USA, and about two-thirds of the population is considered as overweight or obese . Being overweight has adverse effects on health, with several benign health conditions being associated with it, besides the increase in susceptibility to malignancies . For most individuals, who do not have the rare genetic condition caused by a mutation of the leptin gene, that predisposes a person to obesity, maintaining a normal weight should not be considered a challenge. Yet obesity, a preventable condition, has become a modern-day affliction for many individuals who are compelled by biopsychosocial factors to become overweight and are unable to halt the progression to obesity.
Pathophysiologically, for most overweight individuals, the satiety centre in the hypothalamus through its corticohypothalamic connections, including that with the limbic system (see Chapter 1), is often implicated in the need for seeking extra helpings, despite having eaten generous portions. Eating disorders such as bulimia [56,57], which acts through the hypothalamus and its neurological connections, can also be associated with being overweight or obese . Being obese or at a BMI close to obesity can also be associated with gynaecological disease conditions such as subfertility or cancer. Besides, the obese are at greater risk of problems with their pregnancy and labour, as well as associated diabetes, and at an increased risk for any surgical interventions. Obesity can also simultaneously impact on the overall health of the woman including her mental health . Mind–body interaction causing unhappiness may be associated with the transition to becoming overweight and then obese. All these problems can affect reproductive health in the pregnant woman. Any chromosomal alterations that favour obesity in the pregnant woman can be transmitted by transgenerational mechanisms ; this can increase the likelihood of future generations being obese. Specifically, being overweight, and then obese can increase the risk of endometrial cancer  as well as impinge negatively on the overall health of the woman, and the treatment of related diseases.
Obesity and endometrial cancer
Endometrial cancer is the most common gynaecological malignancy in many European countries and in North America . In the UK, an annual frequency of 8475 new cases of endometrial cancer in 2011  made it the most common women’s cancer. In many Eastern European countries, the incidence of endometrial cancer has risen over the last three decades , and is on a par with the rise in obesity. Crosbie et al. have reported that a rise in BMI by 5 kg/m2 is associated with a 1.6-fold increased risk of endometrial cancer . Additionally, anthropometric measures such as waist circumference, and adult weight gain may also be associated with endometrial cancer. Aune et al. have reported  that the summary relative risk (RR) of endometrial cancer was: 1.27 (95% CI, 1.17–1.39, I2 = 71%) for a 10 cm increase in waist circumference, an RR of 1.21 (95% CI, 1.13–1.29, I2 = 0%) per 0.1 unit increment in waist-to-hip ratio, and an RR of 1.30 (95% CI, 1.19–1.41, I2 = 0%) for a 10 cm increase in the hip circumference. In addition, an RR of endometrial cancer of 1.15 (95% CI, 1.09–1.22, I2 = 61%) is associated with a 10 cm increase in height. Renehan et al.  emphasise that such an association between obesity and endometrial cancer is causal, and therefore by avoiding being obese, one could prevent the progression to cancerous changes in the endometrial cells.
The aetiopathogenesis of endometrial cancer
Obese women have hypertrophied adipocytes. Adipocytes release leptin, adiponectin, and tumour necrosis factor that reduce the metabolic response to insulin. Inflammation of the adipocytes causes secretion of adipokinins and cytokines . These modify cellular adhesivity, and disrupt normal tissue architecture along with an increased angiogenesis that is referred to as tumourigenesis or carcinogenesis. Tumourigenesis  is promoted by these alterations in the endometrium at the expense of apoptosis . Obesity is known to play a major role in tumourigenesis of endometrial cancer with a greater effect on endometrioid (type-1) cancer rather than on the non-endometrioid (type-2) cancer. Type-1 disease is more common (80%) than type-2 and has a lower death rate than the latter but still accounts for the major proportion of deaths . In the obese woman, testosterone is aromatised to oestrogen in the adipose tissue . Oestrogen floods the body and enters endometrial cells because there is a relative deficiency of its carrier—the sex hormone binding globulin. In the endometrial cell, oestrogen directly binds to the DNA of the cell to increase transcription, and modify several growth factor (including PI3K-Akt-mTOR and MAPK/ERK1,2) signalling pathways , thereby promoting cellular proliferation. This promotes tumourigenesis in the obese woman. Physiologically, progesterone protects against this oestrogenic proliferative effect in the second half of the menstrual cycle but this action is restricted in disease conditions, such as the polycystic ovarian syndrome, and with the advent of the menopause. Hyperinsulinaemia in the obese also reduces the proportion of insulin-like growth factor (IGF) binding proteins so there is an increase in IGF-1, which promotes cellular proliferation. Moreover, obesity is a chronic inflammatory state that results in elevation of proinflammatory cytokines such as interleukin-6, C-reactive protein and leptin . The proinflammatory markers have an effect on carcinogenesis by affecting immune systems, and disturbing tissue homeostasis, as well as increasing oxidative stress. Despite this understanding of the natural history of the pathological changes in the hyperplastic endometrium, further elucidation is needed about preventing tumourigenesis.
In their three-year multicentre randomised, double masked, placebo-controlled (PEPI trial) , Judd and colleagues found that in the postmenopausal woman, if only unopposed oestrogen was given when compared with giving oestrogen with progesterone; the former treatment was associated with simple (cystic), complex (adenomatous), or atypical hyperplasia that reverted to normal in 94% (n = 34/36) on replacing oestrogen with progesterone. This is similar to the endometrial hyperplasia that occurs naturally in obese women who have hyperoestrogenism because of the biochemical conversion of testosterone in their adipose tissues without the protective effect of progesterone.
Bokhman in 1983 proposed a dualistic model  of endometrial tumourigenesis, which was based on clinical observation, and clinicopathological correlates of a prospective study. The majority of women (65%) in the sample had type-1 cancer, which arose from the hyperplastic endometrium of obese women. These women had highly- and moderately-differentiated tumours (82.3% G1 and G2), with superficial invasion of the myometrium and a high sensitivity to progestogens (80.2%), and with a favourable prognosis (85.6% 5-year survival rate). The other women (35%) in the same sample had poorly-differentiated tumours (62.5% G3), with a propensity to deeper invasion of the myometrium and a high frequency of metastasis to the pelvic lymph nodes (27.8%). This group also had a decreased sensitivity to progestogens (42.5%), and a doubtful prognosis (58.8% 5-year survival rate). Thus, the two types of endometrial cancer need tailored management and follow-up. Prevention of obesity would benefit the incidence of both cancers, although the association of BMI with endometrial cancer is stronger for type-1 . Matias-Giui and Prat  pointed out that four major genetic changes are responsible for type-1 tumourigenesis: silencing of PTEN tumour suppressor gene, microsatellite instability, K-ras mutation, and alteration of beta-catenine gene. In addition, type-2 cancers are associated with a p53 mutation and an overexpression of the Her2/neu oncogene; they are more aggressive than type-1. Molecular classifications help to differentiate the two variants of endometrial cancer and help define management, e.g. distant metastasis is uncommon for the hypermutated MSI associated with low-risk type-1. A consideration of the differences in characteristics of the two cancer types can facilitate discussions on prognosis with the patient and her close family.
Rota et al.  in a pooled analysis of three case–control studies compared the association of BMI with endometrial cancer. They included 1449 patients with cancer and 3822 controls in their assessment. The authors found a non-linear relationship between obesity and endometrial cancer. Renehan et al. in their dose–response meta-analysis  of 24 studies (n = 17 710 cancers) found an overall risk ratio for endometrial cancer of 1.60 (95% CI, 1.52–1.68) for every 5 kg/m2 increase in BMI in the linear model but their optimal model was non-linear with a knot at a BMI of 27 kg/m2. The authors also found that when non-linearity was factored in, the risk of endometrial cancer at a BMI of 40 kg/m2 was tenfold higher than that for women who had a BMI within the normal range. In Rota et al.’s study  the non-linearity between BMI and endometrial cancer became linear when extreme BMI values that were outliers were excluded from the evaluation; their findings then became similar to Renehan’s non-linear model. Nonetheless, keeping outliers in may have added to the interpretation of their evaluation in other ways.
Table 8.2 illustrates the impact of obesity on the management of abdominal pain in a patient (3) who had been previously operated upon for endometrial hyperplasia, and another (4) pregnant woman who had had a previous emergency caesarean for failed instrumental delivery.
Table 8.2 Vignettes: The impact of obesity
Vignette 3: Gynaecology—Abdominal pain, BMI 43: British Caucasian
Vignette 4: Obstetrics—Abdominal pain with pregnancy, BMI 45: British Caucasian
Presentation and management
Mrs RM, a 38-year-old married volunteer for a Charity, with two teenage children, on a gynaecological follow-up visit
Ms GD, a 24-year-old housewife, para 1, cohabiting with her partner
Psychosocial factors increasing vulnerability to psychosomatic disease
Impact on the healthcare system
Other forms of presentations and behaviour
Both Mrs RM and Ms GD were obese, and suffered from disease due to its complications; the obesity also interfered with the management of those complications. Mrs RM was managed appropriately  but the premalignant condition may not have arisen if she had not been obese. Similarly, Ms GD suffered from complications related to childbearing because of her obesity. Medical/social interventions may be required for obesity and its complications, whether related to malignancy or childbearing; this can also impact on close family. Medical personnel need to be aware that modifiable biopsychosociocultural factors can initiate obesity, and then maintain it due to psychosomatic interactions. Prevention of diseases by promoting a normal BMI should be aimed for.
Preventing/treating obesity to prevent endometrial cancer
Several biological mechanisms operate in the association between adiposity and endometrial cancer, with not only the adipose tissue but also the dysfunctional state of the pre-tumour adipose environment being implicated. Preventing endometrial cancer in those with a raised BMI would entail losing weight primarily through lifestyle changes. This appears to be of greater significance in the obese when compared with the overweight members in any sample.
Initiating lifestyle changes that are socioculturally acceptable is conducive to reaching and maintaining a normal weight, which would thus prevent the transformation of the internal milieu that favours the development of endometrial cancer, as there is an inverse relationship between obesity and quality-of-life (QoL). Smits et al. , in their evaluation of cancer survivors treated for early stage endometrial cancer, found that both physical and psychosocial well-being, besides functionality, were inversely related to BMI. Obesity gave these women a social disadvantage, as their peers could discriminate against them because of it. Moreover, the restrictions imposed on their mobility by being overweight could prevent them from pursuing interests independently that could enhance their health. Also, QoL can be further restricted because of the comorbidities associated with obesity such as cardiovascular disease or metabolic syndrome. Reverting to a lower BMI is therefore advantageous but the implementation of a weight loss programme requires a concerted effort by the patient and this may include involving the close family in order to promote such behaviour. This is of greater significance for patients with type-1 endometrial cancers, as many are relatively young compared with those with type-2 cancers. A relatively longer cancer-free survival period needs a concomitant enhanced QoL.
Laskey et al.  emphasise that obesity not only increases the risk of endometrial cancer but also cardiovascular disease; the latter can be fatal for many who survive the treatment of the endometrial cancer. The age-adjusted mortality for endometrial cancer is 2/100 000 with the type-1 oestrogen dependent, low-grade tumours that are associated with obesity; these constitute 80% of all endometrial cancers, and have a >90% 5-year survival. Type-2 are not oestrogen dependent and not commonly associated with obesity; they have a worse 5-year survival rate of only 40–60%, and affect a slightly older population than those with type-1 cancer. Obesity is responsible for increasing the amount of bioavailability of oestrogen and for initiating tumour growth, therefore, its association with the individual’s central obesity makes waist circumference a useful parameter for predicting endometrial cancer. Kabat et al.  reported that making lifestyle changes to reduce obesity can be hindered by the personal opinions of young patients treated for cancer who often believe that the hysterectomy and salpingo-oophorectomy has cured them of cancer so reducing their obesity is no longer of any consequence. Health education to make them aware of the other advantages of weight loss would be of benefit in motivating these individuals to lose weight. In another report, Von Gruenigen et al.  observed that women treated for endometrial cancer who were obese had a lower overall survival rate, and were 25% more likely to die of other causes than that directly related to the cancer when compared with those with a BMI of <40. Carrying out bariatric surgery to reduce weight in the obese female, and thus reducing the risk of endometrial cancer (HR = 0.22; CI, 0.1–0.40) has been discussed by Adams et al. .
Lifestyle alterations to prevent obesity
Lifestyle alterations to prevent obesity or reduce its impact come in a variety of forms. Many of the beneficial methods are free at source, and would be cost-effective if they were successful in preventing the individual from becoming overweight or successful in achieving weight loss if obese. These methods include exercise, dancing, walking, cycling, sport, yoga, and other physical pursuits. Voluntarily participating in a personalised activity regime to promote weight loss may be suitable for some who want flexible regimes to suit them, whereas others may prefer supervised activities in the company of others, though all have to consistently allocate time for these. Habits are inculcated since babyhood, and the child’s early environment has an important role to play. There is limited evidence that breast-feeding can protect against childhood obesity, and the later overweight habitus [82,83]. Food habits are influenced initially by the child’s parents/close relatives and friends, and later by social media/advertisements, and teachers, so healthy eating and exercise to promote positive health often have their origins in childhood. However, seeking healthier pursuits is not always built into a relentless daily work schedule.
Bariatric surgery to reduce the impact of obesity
Conversely, where lifestyle alterations for weight reduction in the obese cannot result in sustained weight loss, bariatric surgery is an option. It has been recently promoted for BMI reduction, which has the additional benefit of preventing endometrial cancer, and its recurrence. However, bariatric surgery needs to be evaluated in the context of its suitability for each individual. Similarly, psychosociocultural factors need to be taken into account, as they were most likely involved in the causation of the obesity, and would be instrumental in the patient’s recovery after surgery, and any of its complications.
Robson et al.  reported that among their Australian population, obesity increased over the last decade by 60% in those of 25–35 years of age and by 80% in those between 35 and 44 years; 3% had a BMI of ≥40kg/m2 in 2012. This indicates that more action is required to prevent obesity, and thus its adverse consequences from acting on these women, including any effects on their offspring. The authors further comment that losing weight is difficult and behavioural modification with or without pharmacological treatments can bring about only modest changes (i.e. about 3 kg). The studies included in the review lack clarity about the duration of the effect of behaviour modification, with few going beyond 10 years. Therefore, surgical approaches, such as bariatric surgery, are gaining attention. Bariatric surgery developed in the 1950s, when it was observed that resecting and shortening the small intestine resulted in weight loss due to malabsorption. One of the types of bariatric surgery—the malabsorption type, known as the Roux-en-Y bypass or biliopancreatic diversion, are based on the previous observations about small intestinal resection. The other type—the restrictive procedure, reduces the capacity of the stomach, and includes the laparoscopic adjustable gastric banding and sleeve gastrectomy, which are easier to perform. Malabsorptive procedures by altering the effective length of the small intestine have an additional effect on the proximal duodenum, resulting in altered neuroendocrine function. The gastric band may need frequent adjustment and liquid/semisolid food, such as ice-cream, can pass through. Colquitt et al. , in a systematic review of non-pregnant adults, reported that bariatric surgery was a better option than non-surgical methods but the authors caution that in these studies, adverse outcomes were under-reported. Moreover, re-operation rates were ignored, and the follow-up visits of their patients were only up to two years.
Regarding pregnancy, there is no evidence that bariatric surgery reduces pregnancy loss, and improves conception rates. Also, because of a rapid change in nutritional status following bariatric surgery, waiting for 1–2 years following surgery before trying to conceive, has been suggested. In managing a pregnancy after gastric banding, there is no clear guideline about whether one should deflate or inflate during pregnancy, although usually, deflation is carried out. It is reported that such surgery reduces the risk of gestational diabetes, hypertension, and macrosomia but the magnitude of the risk reduction is not as great as was hoped . The effect on birth outcomes such as caesarean section is not known, and babies are at an increased risk of growth restriction and being born preterm. Cornthwaite et al.  comment that only a few clinical trials have studied pregnancy after bariatric surgery, so our understanding is based on case reports and observational studies, which have their design limitations.
Certain studies have considered the outcome of pregnancies before and after bariatric surgery, but have been unable to separate the impact of weight loss from the impact of the surgery. Malabsorptive bariatric surgery leads to nutritional deficiencies more often than restrictive surgery . Concerns have been raised about fetal morbidity, even if there may be a reduction of gestational diabetes, and hypertension in the mother. There may be detrimental effects of intestinal hernia and/or nutrition deficiencies in the mother. The psychosocial impact of pregnancy with a gastric band has received scant attention; the preliminary reports of the ENGAGE (ENquiry into women with Gastric banding in pregnancy to Guide management and improve Experience) indicate that information, guidance and support in pregnancy is limited with further clarity being required. However, in this study most had the gastric band inserted privately, so the sample may not have been representative of the overall population. The continuing national prospective study in the UK, using the ‘Obstetrician Surveillance System’ (UKOSS) to investigate pregnancy after gastric banding, may add to this knowledge when its findings are reported. The authors  advocate that these women should receive prepregnancy advice, and be screened and treated for nutritional deficiencies; prescribed low-dose aspirin and vitamin supplementation; screened for gestational diabetes; have serial growth scans along with closer blood pressure, and urinalysis surveillance. Discussions about induction of labour at term should be part of the dialogue with the pregnant woman and her partner. A systemic review has reported a failure of gastric bands in 20–30% patients  in the study samples that they have included.
Notwithstanding the complexities of bariatric surgery and the current status of limited enquiry into any of its detrimental effects, studies have continued to focus on the physical issues, and not the psychological aspects. Hence, the psychosomatic perspective needs further evaluation. One of the reasons for low uptake of bariatric surgery could be the costs, especially where governments and insurance companies  do not provide the funding for the procedure, as well as the aftercare. Furthermore, comparing the cost-effectiveness of bariatric surgery against other alternative options has not been studied comprehensively. The morbidly obese can be considered for bariatric surgery under the NHS, UK, if a structured weight loss programme has been unable to reduce weight and maintain the weight reduction, despite being consistently followed by the individual . A Canadian review  evaluated the available evidence on the direct/indirect costs of bariatric surgery on non-pregnant patients, and concluded that limited information made it impossible to assess generalisability of costs and outcomes/gains. The impact of postings on social media that are critical of procedures/surgeons and hospitals, besides internet ‘blogs’ and ‘chat rooms’ have yet to be evaluated in this context  though such factors may influence patient uptake of such surgery.
Finally, Ligibel et al. and the American Society of Clinical Oncology  have provided guidance to aid physicians in advising women whom they have treated for endometrial cancer regarding weight reduction; the guide can additionally help those physicians who are overweight themselves in not feeling hypocritical when advising obese/overweight patients, regarding their weight reducing regime.
The impact of obesity on childbearing
This is a current issue with obesity having become a global epidemic. A concerted multidisciplinary effort to reduce the effects of obesity on the mother and her child are needed, and the International Weight Management in Pregnancy Collaboration Group has made a position statement .
Impact during pregnancy on the adolescent/child
Studies on pregnancy during adolescence report on the needs exclusive to the adolescent gravidae, who should receive tailored care. They are at an increased risk of complications  such as hypertensive diseases of pregnancy, preterm delivery, low birthweight, and neonatal/infant morbidity and mortality. In the obese adolescent, these problems can be further magnified if she conceives. Additionally, a transgenerational effect promoting obesity can be carried over to the fetus of the obese pregnant mother. Gaillard et al.  reported, in a population-based prospective cohort study in Australia (sample, n = 1392), that a higher prepregnancy BMI was associated with a higher BMI, waist circumference, and waist-to-hip ratio in their adolescent children, who were followed from birth to 17 years of age. A higher prepregnancy BMI and early pregnancy weight gain was associated with a risk of increased adiposity, along with an adverse cardiometabolic profile in the 17-year-olds; the association with the prepregnancy period was stronger than that during pregnancy (OR 1.57; 95% CI, 1.33–1.85 and OR 1.23; 95% CI, 1.03–1.47, respectively). Moreover, these adolescents had a higher waist circumference, waist-to-hip ratio, systolic blood pressure, insulin, glucose, and HOMA-IR (insulin resistance) levels. Part of the study findings were similar to the British mother-child study by Fraser et al. , who found that in their sample (n = 5154), the gestational weight gain during the first 14 weeks was associated with the BMI, waist circumference, and fat mass of their offspring at 9 years. Similarly, Margerison-Zilko et al.  in their sample (n = 5908) found an association of early pregnancy weight gain with adverse cardiometabolic effects in their children at 6 years of age. Karachailiou et al.  found an association in their mother-child pairs (n = 977) between first trimester maternal weight gain and childhood obesity at 2–4 years of age. Increased fat deposition during pregnancy may lead to higher placental transfer of nutrients, and subsequent programming of the offspring’s adiposity, along with an adverse cardiometabolic profile . Therefore, prevention of the transgenerational effect of obesity on several health parameters during adulthood requires early action to prevent the child from becoming an obese teenager or obese adult mother.
Impact on ovulation and fecundity
An obese woman can ovulate normally and be fertile, yet she may have a fetal loss before 24 weeks’ gestation—a miscarriage, repeatedly. Such a loss of three or more consecutive pregnancies is known as recurrent miscarriage in Europe, whereas the American Society considers the loss of two or more pregnancies as recurrent miscarriage. Teklenburg et al. observed that pregnancy loss is associated with the implantation of embryos with chromosomally abnormal cells and/or biosensory failure of the decidualised endometrium , which interfere with implantation. Yet, the underlying causes of recurrent miscarriage remain elusive. The probability of achieving pregnancy in one menstrual cycle, namely, the average fecundity rate, was 20%; it was 1–5% in the subfertile but 60% in the superfertile, with the obese being included in the latter category . Bhandari et al. reported  on the reproductive failures due to recurrent miscarriage, assessed at an implantation clinic. They analysed the impact of obesity on the time-to-pregnancy interval in women with recurrent miscarriage, when compared with normal weight women, and the patterns of pregnancy loss in women with such a history. They found that an obesogenic environment may have a negative influence on the endometrium, with resultant early miscarriages of euploid fetuses. Their study was limited by recall bias, and age at presentation may not have reflected the age at pregnancy loss, due to the varying testing protocols from referral clinics. The possible effect of obesity on the preparation for pregnancy by the endometrium remains controversial however, with studies reporting for  and against  this hypothesis. Ledger, in a commentary  remarks that weight loss would probably not prevent such miscarriages in the obese as, in his opinion, these miscarriages could be due to subtle chromosomal abnormalities that could only be detected by microarray comparative genomic hybridisation and next generation sequencing, which were not used in the study by Bhandari et al. .
Conversely, obesity can reduce fecundity and result in infertility in patients with polycystic ovarian syndrome (PCOS). PCOS occurs in 5–10% of women and often presents with menstrual irregularities  and hirsutism. Patients with PCOS have polycystic ovarian morphology, along with ovarian dysfunction and hyperandrogenism with elevated serum levels of LH, in addition to insulin resistance. Insulin resistance leads to the reproductive and metabolic features of PCOS. Besides the gynaecological symptoms and features of hyperandrogenism, the women are at increased risk of type 2 diabetes and cardiovascular events. Markers such as adipocytokines, irisin, PAI-1, and zonulin are associated with insulin resistance, as are potential new markers such as resistin, leptin, kisspeptin, and ghrelin, but the significance of the latter is controversial. Weight reduction is of immense benefit in reversing the pathological changes and facilitating ovulation in the obese who are anovulatory. Wild et al.  in a literature review, concluded that women were at risk of cardiovascular diseases if they had PCOS with obesity, hypertension, impaired glucose tolerance, dyslipidaemia, subclinical vascular disease, and were smokers. They were at a higher risk of cardiovascular diseases if they had PCOS along with metabolic syndrome or type 2 diabetes. These obese women could also be at risk of mood disorders. This calls for early implementation of lifestyle changes to reduce weight and improve the metabolic profile, thereby preventing cardiovascular disease and promoting well-being. Weight reduction also improves fecundity in those who have anovulation, and facilitates implantation of the embryo. Adolescents can have polycystic ovarian morphology detected on a routine ultrasonography of the pelvis without a metabolic abnormality or anovulation, and often remain healthy . This would indicate that no treatment is needed based solely on the chance imaging of ovarian morphology in this young group. However, the significance in adolescents of symptoms/signs of anovulatory cycles, hyperandrogenemia, hyperandrogenism (hirsutism, acne, or alopecia), or ovarian findings on ultrasound, is not established. These clinical features can regress with time, thereby their clinical significance is unclear , and diagnostic features of PCOS in adolescents have yet to be established. Furthermore, individualisation of management is necessary, with reduction of weight and smoking if indicated in the obese; behavioural changes could have a beneficial effect on metabolism and physical and mental well-being, thus there is a need for such attitudes in health promotion. Paying attention to gut microbiota may be beneficial but needs further research. Medication such as metformin or antidepressants with psychotherapy can have a role in patients who have the adverse psychosomatic manifestations of PCOS. Ovarian drilling or bariatric surgery can also have a role in management, if lifestyle changes/medical management have no or limited impact on obesity and subfertility, and the patient is keen to consider invasive procedures with uncertain outcomes.
Impact on subcutaneous fat thickness and obstetric outcomes
Kershaw and Flier reported  that adipose tissue contains stromovascular cells, connective tissue matrix, nerve tissue, and immune cells, as well as adipocytes, and function as a neuroendocrine organ. It responds to the messages from the central nervous system and hypothalamopituitary axis (see Chapter 1), along with responses to local factors, such as cytokines, adiponectin, complement components, plasminogen activator, resistin, and hormones of the renin-angiotensin system. Adipose tissue also metabolises sex steroids and glucocorticoids, so has overarching effects affecting metabolism, and inflammation. Over accumulation of adipose tissue, as in the obese, can therefore cause chronic inflammatory effects. The metabolic effects and inflammation during pregnancy can add to the existing effects of obesity , and lead to complications such as metabolic syndrome, pre-eclampsia, fetal and neonatal effects, haemorrhage, and wound problems. While central obesity increases adverse effects on the cardiovascular system and is associated with diabetes , peripheral obesity is protective. Fox et al.  reported a correlation between abdominal subcutaneous fat thickness (SFT) and cardiovascular diseases and obesity, though visceral fat was more strongly related. In a prospective longitudinal study, Kennedy et al.  investigated (sample, n = 1510) the correlation of SFT measured by ultrasound during the first (11–14 weeks) and second (18–22 weeks) trimesters at 21.2 mm and 20.3 mm, respectively, and associated these with pregnancy complications. Of the 1385 women who had complete datasets, 54% were overweight or obese. A correlation of SFT with gestational diabetes, hypertensive disease, preterm delivery, low birthweight, caesarean birth, neonatal respiratory distress syndrome, and admission to the neonatal intensive care unit was confirmed. SFT was a better predictor of adverse pregnancy outcomes than BMI, with the authors suggesting that the SFT was a better predictor of central obesity.
Obesity is a risk factor for preterm labour, namely delivery before 37 completed weeks of pregnancy. It is not yet clear how obesity initiates preterm labour but inflammatory, neuroendocrine, and lifestyle factors  are probably implicated. Adipose tissue produces adipokines that stimulate secretion of proinflammatory cytokines along with gestational weight gain , which in turn increases the likelihood of preterm labour. Faucher et al. reviewed the relationship between gestational weight gain above the Institute of Medicine’s (IOM) recommendations and preterm birth in the obese , and assessed whether there were differences in risk by the class of obesity. The authors observed that it is widely recognised that an increased risk of preterm labour in the obese relates to medical complications of pregnancy. The conclusion from the four studies meeting the inclusion criteria from the USA (n = 10 171) and one from Peru, was that obese women with gestational weight gain above that recommended by the IOM (>9 kg total weight gain) were at an increased risk of preterm birth (adjusted OR 1.54; 95% CI, 1.09–2.16). There was considerable heterogeneity between the studies, implying a need for further investigations.
Brownfoot et al. , in a randomised controlled trial from Australia, investigated whether routine weighing at each antenatal visit would lead to a difference in gestational weight gain, and weight gain within the IOM recommendations. The intervention was by weighing at each visit, followed by counselling (n = 386) by the clinician, while the control group (n = 396) had routine care with weighing at booking and at 36 weeks. The secondary outcome was maternal and neonatal morbidity. There was no significant difference in weight between the intervention (0.54 kg/week) and the control (P = 0.53) (P = 0.63) groups respectively, nor in the excessive weight gain beyond that recommended by the IOM (75% in the intervention and 71% in the control; P = 0.21). Secondary outcomes between the groups were similar. The authors concluded that regular weighing was of no benefit in altering weight gain. Preston and Norman  in their commentary, point out that the large sample size in Brownfoot et al.’s trial is its strength, along with their use of calibrated scales in addition to the clinician’s discussion with the patients in the intervention group. Nonetheless, blind allocation was not possible and whether both groups had standard advice was unclear. However, if repeated weighing is of no value, alternative measures to minimise weight gain are needed. Notwithstanding, there are other benefits of repeat weighing such as prescribing drugs in late pregnancy, and feedback is all important to women who are planning a future pregnancy.
Impact on maternal and perinatal outcomes
Lee and colleagues reported from a retrospective, cohort study  that compared perinatal outcomes between elective induction of labour at term or expectant management of obese women carrying singletons (n = 74 725). Their maternal outcome measures included delivery mode, severe perineal lacerations, postpartum haemorrhage, chorioamnionitis and fetal macrosomia, shoulder dystocia, brachial plexus injury, and respiratory distress syndrome. Induction of labour at 37–40 weeks reduced the odds of caesarean delivery, without increasing the risks of adverse outcomes in the puerperium when compared with expectant management. When labour was electively induced in nulliparae at 37 weeks, the odds of caesarean delivery were lower (OR 0.55; 95% CI, 0.34–0.90) and at 39 weeks (OR 0.77; 95% CI, 0.63–0.95), when compared with expectant management. For those with expectant management of labour at 37 weeks, the findings were OR 0.39; 95% CI, 0.24–0.64, and at 39 weeks OR 0.67; 95% CI, 0.56–0.81. Elective induction of labour at 39 weeks decreased the odds of caesarean for both nulliparae and multiparous women. Moreover, there was a reduction of macrosomia in the mothers who had elective induction of labour but there were no differences between groups regarding operative vaginal delivery or perineal lacerations, and the neonatal parameters. Thus, induction of labour for obese gravidae seems a viable option but further evaluation is proposed.
Dodd et al. evaluated neonatal anthropometry  after providing antenatal dietary and lifestyle advice to their pregnant sample in Australia. This was a randomised controlled trial with women randomised to either lifestyle advice about diet, exercise, and behavioural strategies delivered by a research dietician during pregnancy, or receiving standard care. Secondary outcome measures included measuring skinfold thickness, neonate body circumference, and bio-impedance analysis of fat-free mass. Measurements were obtained from 488 neonates of mothers in the Lifestyle Advice Group and 482 from mothers of the Standard Care Group. The authors concluded that there was no difference in the neonates born to mothers who were overweight/obese, and were given lifestyle advice from those born to women who received standard care. Maternal obesity and infant outcomes were part of the discussions of a recent congress, where it was highlighted that although there was an association between maternal obesity and infant outcomes, the evidence was limited for a causal relationship ; further research is warranted.
The preceding deliberations confirm the deleterious effect of obesity on childbearing with considerable morbidity on the individual affected, which can also impact on the conceptus and future offspring. Primary prevention by practising suitable lifestyle activities that promote a normal BMI, and are economically sound, besides tertiary prevention by bariatric surgery, which is expensive, have been discussed.
According to the WHO, the global epidemic of obesity has generated a plethora of preventable disease conditions in its wake. Obesity now affects 41 million children under the age of five, worldwide . In their directive on population-based approaches to childhood obesity, the WHO has identified the need for member states to curb childhood obesity  by within-government policies for prevention and intervention, population-wide policies through laws and social marketing campaigns, and community-based interventions tailored to the local environment. Prevention of obesity in childhood could lower its frequency in teenagers and adults, and the unnecessary drain on the economy from the treatments related to it, along with the management of diseases due to its psychosomatic repercussions. The woman is receptive, and accessible during pregnancy and the postpartum, to advice on dietary modification and exercise; such advice would also benefit a supportive partner. Hence, promoting health education for the couple along with inculcation of such values into the infant/child would be a cost-effective strategy to prevent obesity, including its transgenerational effects. A campaign aimed at vulnerable subgroups , such as teenagers and oral contraceptive users, to reduce HPV infection by using barrier contraceptives has also been advocated; it could work in the motivated. The promotion of the HPV vaccination in 11–12-year-old children as a universal prophylaxis for cervical cancer in developed countries has been questioned [123,124], and ethical violations in vaccine promotion in low- and middle-income populations have been reported .
Primary and secondary prevention of cancer and obesity may be an economically sound approach to promoting positive psychosomatic health but such healthcare provision may not be available to many women, globally. This results in tertiary prevention, and treatment of preventable diseases along with their complications, in many populations. Furthermore, sociocultural deterrents need further recognition to effectively reduce the local disease burden of gynaecological cancer and obesity.
Reducing the prevalence of cervical cancer by preventing carcinogenic HPV infection through primary and secondary prevention has already helped reduce its incidence in the West. This needs promotion in low–middle-income countries, yet the practicalities of carrying out such forms of women’s health promotion under challenging circumstances, and the inflexible sociocultural norms for adolescents and adults within diverse populations, requires local, national, and global collaborations. HPV vaccination as a form of primary prevention was developed against 70% of carcinogenic HPV subtypes, thus advice for additional protection against infection by using barrier methods remains relevant, globally. Concomitant cervical screening also needs to be maintained for HPV genotypes not targeted in the vaccine that could infect and cause CIN. Moreover, in the vaccinated, adhering to condom protection should continue, as the protection against infection by HPV subtypes included in the vaccine run out within a decade, and the need for a booster dose is yet to be evaluated.
Obesity is thought to play a major aetiological role in the development of endometrioid tumours but not of non-endometrioid tumours of the uterus. Therefore, the prevention of obesity, and limiting harm by weight reduction, is a valuable proposition for reducing the incidence of endometrial cancer. Lifestyle alterations should be practised by all who are overweight. Behavioural change for reducing obesity would be worthwhile both in terms of current health promotion, and our responsibility towards promoting the health of future generations. Prudent use of our limited healthcare resources is better taught by example. Prevention of cancer and obesity in women and adolescents by earlier action on the overweight habitus should be prime examples.
Measures to prevent being overweight and obese should also be prioritised to reduce its major impact on the physical, mental, and social health associated with these conditions; the additional benefit in preventing the metabolic syndrome and cardiovascular disease with detrimental mind–body interactions, reinforces its significance. Over-screening or over-enthusiastic treatment, which may cause psychological/physical harm without necessarily benefiting the individual, merits research. A cautious management approach matched to the person’s biopsychosociocultural circumstances should satisfy the individual, and limit unnecessary expenditure on treatment. In relation to cancer and obesity, disease prevention seems more cost-effective than cure. Investigation into psychosomatic interactions that are associated with cancer and obesity, including the initiation by biopsychosociocultural factors, deserves wider recognition.
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